| 1. |
- Brusselaers, Nele, et al.
(författare)
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Menopausal hormone therapy and the risk of esophageal and gastric cancer
- 2017
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Ingår i: International Journal of Cancer. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0020-7136 .- 1097-0215.
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Tidskriftsartikel (refereegranskat)abstract
- A protective effect of female sex hormones has been suggested to explain the male predominance in esophageal and gastric adenocarcinoma, but evidence is lacking. We aimed to test whether menopausal hormone therapy (MHT) decreases the risk of these tumors. For comparison, esophageal squamous cell carcinoma was also assessed. This population-based matched cohort study included all women who had ever used systemic MHT in Sweden in 2005-2012. A comparison cohort of non-users of MHT was matched to the MHT-users regarding age, parity, thrombotic events, hysterectomy, diabetes, obesity, smoking-related diseases, and alcohol-related diseases. Individuals with any previous cancer were excluded. Data on MHT use, cancer, comorbidity, and mortality were collected from well-established Swedish nationwide registers. Odds ratios (OR) with 95% confidence intervals (CI) were calculated using conditional logistic regression. Different MHT regimens and age groups were compared in sub-group analyses. We identified 290,186 ever-users and 870,165 non-users of MHT. Ever-users had decreased ORs of esophageal adenocarcinoma (OR=0.62, 95% CI 0.45-0.85, n=46), gastric adenocarcinoma (OR=0.61, 95% CI 0.50-0.74, n=123), and esophageal squamous cell carcinoma (OR=0.57, 95% CI 0.39-0.83, n=33). The ORs were decreased for both estrogen-only MHT and estrogen and progestin combined MHT, and in all age groups. The lowest OR was found for esophageal adenocarcinoma in MHT-users younger than 60 years (OR=0.20, 95% CI 0.06-0.65). Our study suggests that MHT-users are at a decreased risk of esophageal and gastric adenocarcinoma, and also of esophageal squamous cell carcinoma. The mechanisms behind these associations remain to be elucidated.
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| 2. |
- Eriksson, Louise, et al.
(författare)
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Time from breast cancer diagnosis to therapeutic surgery and breast cancer prognosis : A population-based cohort study
- 2018
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Ingår i: International Journal of Cancer. - Stockholm : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 143:5, s. 1093-1104
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Tidskriftsartikel (refereegranskat)abstract
- Theoretically, time from breast cancer diagnosis to therapeutic surgery should affect survival. However, it is unclear whether this holds true in a modern healthcare setting in which breast cancer surgery is carried out within weeks to months of diagnosis. This is a population- and register-based study of all women diagnosed with invasive breast cancer in the Stockholm-Gotland healthcare region in Sweden, 2001-2008, and who were initially operated. Follow-up of vital status ended 2014. 7,017 women were included in analysis. Our main outcome was overall survival. Main analyses were carried out using Cox proportional hazards models. We adjusted for likely confounders and stratified on mode of detection, tumor size and lymph node metastasis. We found that a longer interval between date of morphological diagnosis and therapeutic surgery was associated with a poorer prognosis. Assuming a linear association, the hazard rate of death from all causes increased by 1.011 (95% CI 1.006-1.017) per day. Comparing, for example, surgery 6 weeks after diagnosis to surgery 3 weeks after diagnosis, thereby confers a 1.26-fold increased hazard rate. The increase in hazard rate associated with surgical delay was strongest in women with largest tumors. Whilst there was a clear association between delays and survival in women without lymph node metastasis, the association may be attenuated in subgroups with increasing number of lymph node metastases. We found no evidence of an interaction between time to surgery and mode of detection. In conclusion, unwarranted delays to primary treatment of breast cancer should be avoided. What's new? Theoretically, an increase in the interval between breast-cancer diagnosis and therapeutic surgery should affect survival, but it is uncertain whether that holds true in a modern healthcare setting. In this prospective study, the authors found that even fairly short delays (on the order of days or weeks) from diagnosis to surgery are associated with decreased survival. These results suggest that the time between diagnosis and therapeutic surgery should be kept as short as possible without hampering diagnostic work-up and preoperative patient optimization.
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| 3. |
- He, Wei, et al.
(författare)
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Cause-specific mortality in women with breast cancer in situ
- 2016
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Ingår i: International Journal of Cancer. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0020-7136 .- 1097-0215.
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Tidskriftsartikel (refereegranskat)abstract
- The long-term mortality remains unknown in women diagnosed with breast cancer in situ (BCIS). Here, we assessed the cause-specific mortality in BCIS patients. This population-based cohort study included 12,243 women diagnosed with BCIS in Sweden between 1980 and 2011. Patients were followed until death, emigration, or 31 December 2013, whichever came first. The 30-year cumulative incidence of breast cancer-specific mortality was 6.3%, which is considerably lower than 49.7% observed for other-cause mortality. Women diagnosed with BCIS were more likely to die from breast cancer (standardized mortality ratio [SMR], 3.85; 95% CI, 3.47-4.27) but less likely to die from cardiovascular disease (SMR, 0.88; 95% CI, 0.82-0.95) than women in the general population. Specifically, the SMRs for breast cancer-specific mortality decreased over time from 5.19 (95% CI, 3.95-6.81) among BCIS diagnosed during 1980-1989 to 3.03 (95% CI, 2.35-3.91) among those diagnosed during 2000-2011. Furthermore, higher risk of death from other causes was seen among those with older age at BCIS diagnosis, lower levels of education, nulliparity, higher Charlson Comorbidity Index, and being hospitalized before BCIS diagnosis; whereas, lower risk of death from breast cancer was seen among BCIS diagnosed in the later time period and those with younger age at first birth. We conclude that most women diagnosed with BCIS die from causes other than breast cancer, which highlights the need for actions not only to reduce nonbreast cancer mortality but also to identify patient where extensive curative BCIS treatment is not adding to survival.
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| 4. |
- Lagergren, Jesper, et al.
(författare)
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Prognosis following cancer surgery during holiday periods
- 2017
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Ingår i: International Journal of Cancer. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0020-7136 .- 1097-0215.
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Tidskriftsartikel (refereegranskat)abstract
- Surgery is the mainstay curative treatment in most cancer. We aimed to test the new hypothesis that cancer surgery performed during holiday periods is associated with worse long-term prognosis than for non-holiday periods. This nationwide Swedish population- based cohort study included 228,927 patients during 1997-2014 who underwent elective resectional surgery for a cancer where the annual number of resections was over 100. The 16 eligible cancer sites were grouped into 10 cancer groups. The exposure, holiday periods, was classified as wide (14-weeks) or narrow (7-weeks). Surgery conducted inside versus outside holiday periods was compared regarding overall disease-specific (main outcome) and overall all-cause (secondary outcome) mortality. Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, sex, comorbidity, hospital volume, calendar period, and tumor stage. Surgery conducted during wide and narrow holiday periods were associated with increased HRs of disease-specific mortality for cancer of the breast (HR 1.08, 95% CI 1.03-1.13 and HR 1.06, 95% CI 1.01-1.12) and possibly of cancer of the liver-pancreas-bile ducts (HR 1.09, 95% CI 0.99-1.20 and HR 1.12, 95% CI 0.99-1.26). Sub- groups with cancer of the colon-rectum, head-and-neck, prostate, kidney-urine bladder, and thyroid also experienced statistically significantly worse prognosis following surgery conducted during holiday periods. No influence of surgery during holiday was detected for cancer of the esophagus-stomach, lung, or ovary-uterus. All-cause HRs were similar to the disease-specific HRs. The prognosis following cancer surgery might not be fully maintained during holiday periods for all cancer sites.
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| 5. |
- Lee, Myeongjee, et al.
(författare)
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Differences in survival for patients with familial and sporadic cancer
- 2016
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Ingår i: International Journal of Cancer. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0020-7136 .- 1097-0215.
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Tidskriftsartikel (refereegranskat)abstract
- Family history of cancer is a well-known risk factor but the role of family history in survival is less clear. The aim of this study was to investigate the association between family history and cancer survival for the common cancers in Sweden. Using the Swedish population-based registers, patients diagnosed with the most common cancers were followed for cancer-specific death during 1991-2010. We used multivariate proportional hazards (Cox) regression models to contrast the survival of patients with a family history of cancer (individuals whose parent or sibling had a concordant cancer) to the survival of patients without a family history. Family history of cancer had a modest protective effect on survival for breast cancer (hazard ratio (HR) = 0.88, 95% confidence interval (95% CI) = 0.81 to 0.96) and prostate cancer (HR = 0.82, 95% CI = 0.75 to 0.90). In contrast, family history of cancer was associated with worse survival for nervous system cancers (HR = 1.24, 95% CI = 1.05 to 1.47) and ovarian cancer (HR = 1.20, 95% CI = 1.01 to 1.43). Furthermore, the poorer survival for ovarian cancer was consistent with a higher FIGO stage and a greater proportion of more aggressive tumors of the serous type. The better survival for patients with a family history of breast and prostate cancer may be due to medical surveillance of family members. The poor survival for ovarian cancer patients with an affected mother or sister is multifactorial, suggesting that these cancers are more aggressive than their sporadic counterparts.
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| 6. |
- Strand, Fredrik, et al.
(författare)
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Longitudinal fluctuation in mammographic percent density differentiates between interval and screen-detected breast cancer
- 2016
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Ingår i: International Journal of Cancer. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0020-7136 .- 1097-0215.
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Tidskriftsartikel (refereegranskat)abstract
- Interval breast cancer (IC) has a more aggressive phenotype and higher mortality than screen-detected cancer (SDC). In this case-case study, we investigated whether the size of longitudinal fluctuations in mammographic percent density (PD fluctuation) was associated with the ratio of IC versus SDC among screened women with breast cancer. The primary study population consisted of 1,414 postmenopausal breast cancer cases, and the validation population of 1,241 cases. We calculated PD fluctuation as the quadratic mean of deviations between actual PD and the long-term trend estimated by a mixed effects model. In a logistic regression model we examined the association between PD fluctuation and IC versus SDC including adjustments for PD at last screening, age at diagnosis, BMI and hormone replacement therapy. All statistical tests were two-sided. There were 385 IC and 1,029 SDC in the primary study population, with PD fluctuations of 0.44 and 0.41 respectively (p = 0.0309). After adjustments, PD fluctuation was associated with an increased ratio of IC versus SDC, with an estimated per-standard deviation odds ratio of 1.17 (95% CI = 1.03-1.33), compared to 1.19 (95% CI = 1.04-1.38) in the validation population. In screened women with breast cancer, high fluctuation in mammographic percent density was associated with an increased ratio of IC versus SDC. Whether this is entirely related to a reduced mammographic detectability or to a biological phenotype promoting faster tumor growth remains to be elucidated.
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| 7. |
- Tanskanen, T., et al.
(författare)
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Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci
- 2018
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Ingår i: International Journal of Cancer. - Stockholm : Wiley. - 0020-7136 .- 1097-0215. ; 142:3, s. 540-546
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have been successful in elucidating the genetic basis of colorectal cancer (CRC), but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome-wide association study in 1,701 CRC cases and 14,082 cancer-free controls from the Finnish population. A total of 9,068,015 genetic variants were imputed and tested, and 30 promising variants were studied in additional 11,647 cases and 12,356 controls of European ancestry. The previously reported association between the single-nucleotide polymorphism (SNP) rs992157 (2q35) and CRC was independently replicated (p=2.08 x 10(-4); OR, 1.14; 95% CI, 1.06-1.23), and it was genome-wide significant in combined analysis (p=1.50 x 10(-9); OR, 1.12; 95% CI, 1.08-1.16). Variants at 2q35, 6p21.2, 8q23.3, 8q24.21, 10q22.3, 10q24.2, 11q13.4, 11q23.1, 14q22.2, 15q13.3, 18q21.1, 20p12.3 and 20q13.33 were associated with CRC in the Finnish population (false discovery rate<0.1), but new risk loci were not found. These results replicate the effects of multiple loci on the risk of CRC and identify shared risk alleles between the Finnish population isolate and outbred populations.
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| 8. |
- Wennerberg, Erik, et al.
(författare)
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Doxorubicin sensitizes human tumor cells to NK and T cell-mediated killing by augmented TRAIL-receptor signaling
- 2013
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Ingår i: International Journal of Cancer. - Stockholm : Karolinska Institutet, Dept of Oncology-Pathology. - 1097-0215 .- 0020-7136.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Doxorubicin (DOX) is an anthracycline antibiotic that is widely used to treat different types of malignancy. In this study, it was studied whether DOX could be used to render tumor cells susceptible to apoptosis by NK and T cells. Pretreatment with subapoptotic doses of DOX sensitized tumor cell lines of various histotypes to both NK and T cells resulting in a 3.7 to 32.7% increase in lysis (2.5 mean fold increase, p < 0.0001) and a 2.9 to 14.2% increase in lysis (3.0 mean-fold increase, p < 0.05), respectively. The sensitizing effect of the drug was primarily dependent on the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/TRAIL-receptor signaling, but not on Fas-ligand, perforin, NKG2D or DNAM-1. The central role of the TRAIL signaling pathway was further supported by an increased expression of TRAIL-R2 on DOX-treated tumor cells and by downregulation of cellular FLICE inhibitory protein, the inhibitors of death receptor-mediated apoptosis. Compared to untreated cells, pretreatment of tumor cells with DOX showed increased processing and activation of caspase-8 on coculture with NK or T cells. The significance of this treatment strategy was confirmed using a xenogeneic tumor-bearing mouse model. Tumor progression was delayed in mice that received either NK cells (p < 0.05) or T cells (p < 0.0001) following DOX treatment compared to mice receiving either cell type alone. Moreover, combined infusion of both NK and T cells following DOX treatment not only delayed tumor progression but also significantly improved the long-term survival (p < 0.01). Based on these findings, it was proposed that DOX can be used to improve the efficacy of adoptive cell therapy in patients with cancer.
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| 9. |
- Xie, Shao-Hua, et al.
(författare)
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A model for predicting individuals' absolute risk of esophageal adenocarcinoma : moving toward tailored screening and prevention
- 2016
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Ingår i: International Journal of Cancer. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0020-7136 .- 1097-0215.
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Tidskriftsartikel (refereegranskat)abstract
- Esophageal adenocarcinoma (EAC) is characterized by rapidly increasing incidence and poor prognosis, stressing the need for preventive and early detection strategies. We used data from a nationwide population-based case-control study, which included 189 incident cases of EAC and 820 age- and sex-matched control participants, from 1995 through 1997 in Sweden. We developed risk prediction models based on unconditional logistic regression. Candidate predictors included established and readily identifiable risk factors for EAC. The performance of model was assessed by the area under receiver operating characteristic curve (AUC) with cross-validation. The final model could explain 94% of all case patients with EAC (94% population attributable risk) and included terms for gastro-esophageal reflux symptoms or use of antireflux medication, body mass index (BMI), tobacco smoking, duration of living with a partner, previous diagnoses of esophagitis and diaphragmatic hernia and previous surgery for esophagitis, diaphragmatic hernia or severe reflux or gastric or duodenal ulcer. The AUC was 0.84 (95% confidence interval [CI] 0.81-0.87) and slightly lower after cross-validation. A simpler model, based only on reflux symptoms or use of antireflux medication, BMI and tobacco smoking could explain 91% of the case patients with EAC and had an AUC of 0.82 (95% CI 0.78-0.85). These EAC prediction models showed good discriminative accuracy, but need to be validated in other populations. These models have the potential for future use in identifying individuals with high absolute risk of EAC in the population, who may be considered for endoscopic screening and targeted prevention.
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| 10. |
- Xie, Shao-Hua, et al.
(författare)
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A possible link between famine exposure in early life and future risk of gastrointestinal cancers : implications from age-period-cohort analysis
- 2016
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Ingår i: International Journal of Cancer. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1097-0215 .- 0020-7136.
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Tidskriftsartikel (refereegranskat)abstract
- The Chinese famine in 1958-1962 was one of the worst in human history, but its potential influence on cancer risks is uncertain. Using cancer incidence data in Shanghai, China, during 1983-2007, we calculated age-specific incidence rates of gastrointestinal cancers in birth cohorts exposed to the Chinese famine in different periods of life and a non-exposed reference cohort. Age-period-cohort regressions estimated the overall relative risks of gastrointestinal cancers in each birth cohort. A total of 212,098 new cases of gastrointestinal cancer were identified during the study period (129,233 males and 82,865 females), among whom 18,146 had esophageal cancer, 71 ,011 gastric cancer, 55,864 colorectal cancer, 42,751 liver cancer, 9,382 gallbladder cancer, and 14,944 had pancreatic cancer. The risk of esophageal, gastric, colorectal, and liver cancers was higher in cohorts exposed to the Chinese famine in early life than in the reference cohort, except for esophageal cancer in women. The risk of esophageal, liver, and colorectal cancers was particularly high in men exposed to famine during early childhood (0-9 years). There were no clear associations between famine exposure and the risk of pancreatic or gallbladder cancer. This study suggests an increased risk of esophageal, gastric, liver, and colorectal cancers associated with childhood exposure to the Chinese famine. These findings indicate a need for further investigations confirming the results and identifying the underlying mechanisms.
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| 11. |
- Yang, Haomin, et al.
(författare)
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Time-dependent risk of depression, anxiety, and stress-related disorders in patients with invasive and in situ breast cancer
- 2017
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Ingår i: International Journal of Cancer. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0020-7136 .- 1097-0215.
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Tidskriftsartikel (refereegranskat)abstract
- Despite concerns about the mental health of breast cancer patients, little is known regarding the temporal risk pattern and risk factors of common mental disorders among these patients. We estimated standardized incidence ratios (SIRs) of depression, anxiety and stress-related disorders in a Swedish nationwide cohort of 40,849 women with invasive and 4,402 women with in-situ breast cancer (2001- 2010, median follow-up = 4.5 years). The impact of patient, tumor and treatment characteristics was analyzed using flexible parametric survival models in a regional cohort of 7,940 invasive breast cancer patients (2001-2013, median follow-up = 7.5 years). Women with invasive breast cancer showed increased rates of depression, anxiety and stress-related disorders [overall SIR (95% CI) = 1.57 (1.46- 1.69), 1.55 (1.43-1.68) and 1.77 (1.60-1.95), respectively]. SIRs were highest shortly after diagnosis, but remained increased up to 5 years. Younger age at diagnosis, comorbidity, higher-grade disease, lymph node involvement and chemotherapy were independently associated with the risk of depression and anxiety in invasive cancer patients, with chemotherapy and higher-grade disease conferring short-term risk only, while comorbidities were mainly associated with late-onset events. No clinical risk factors were identified for stress-related disorders except for a greater risk associated with younger age. Patients with in-situ cancer only showed an increased incidence of stress-related disorders during the first six months after diagnosis [SIR (95% CI) = 2.76 (1.31-5.79)]. The time-dependent risk profile of invasive cancer patients may guide health care professionals for timely and targeted psycho-oncologic interventions.
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| 12. |
- Aleksandrova, Krasimira, et al.
(författare)
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Adiposity, mediating biomarkers and risk of colon cancer in the European prospective investigation into cancer and nutrition study
- 2014
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Ingår i: International Journal of Cancer. - : Wiley-Blackwell. - 0020-7136 .- 1097-0215. ; 134:3, s. 612-621
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Tidskriftsartikel (refereegranskat)abstract
- Adiposity is a risk factor for colon cancer, but underlying mechanisms are not well understood. We evaluated the extent to which 11 biomarkers with inflammatory and metabolic actions mediate the association of adiposity measures, waist circumference (WC) and body mass index (BMI), with colon cancer in men and women. We analyzed data from a prospective nested case-control study among 662 incident colon cancer cases matched within risk sets to 662 controls. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. The percent effect change and corresponding CIs were estimated after adjusting for biomarkers shown to be associated with colon cancer risk. After multivariable adjustment, WC was associated with colon cancer risk in men (top vs. bottom tertile RR 1.68, 95% CI 1.06-2.65; ptrend = 0.02) and in women (RR 1.67, 95% CI 1.09-2.56; ptrend = 0.03). BMI was associated with risk only in men. The association of WC with colon cancer was accounted mostly for by three biomarkers, high-density lipoprotein cholesterol, non-high-molecular-weight adiponectin and soluble leptin receptor, which in combination explained 46% (95% CI 37-57%) of the association in men and 50% (95% CI 40-65%) of the association in women. Similar results were observed for the associations with BMI in men. These data suggest that alterations in levels of these metabolic biomarkers may represent a primary mechanism of action in the relation of adiposity with colon cancer. Further studies are warranted to determine whether altering their concentrations may reduce colon cancer risk.
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| 13. |
- Allen, Naomi E., et al.
(författare)
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Macronutrient intake and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition
- 2013
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 132:3, s. 635-644
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have suggested that dietary factors may be important in the development of bladder cancer. We examined macronutrient intake in relation to risk of urothelial cell carcinoma among 469,339 men and women in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by sex, age at recruitment and centre and further adjusted for smoking status and duration, body mass index and total energy intake. After an average of 11.3 years of follow-up, 1,416 new cases of urothelial cell carcinoma were identified. After allowing for measurement error, a 3% increase in the consumption of energy intake from animal protein was associated with a 15% higher risk (95% confidence interval [CI]: 330%; ptrend = 0.01) and a 2% increase in energy from plant protein intake was associated with a 23% lower risk (95% CI: 367%, ptrend = 0.006). Dietary intake of fat, carbohydrate, fibre or calcium was not associated with risk. These findings suggest that animal and/or plant protein may affect the risk of urothelial cell carcinoma, and examination of these associations in other studies is needed.
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| 14. |
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| 15. |
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| 16. |
- Andersson, Kristin, et al.
(författare)
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Prospective study of genital human papillomaviruses and nonmelanoma skin cancer.
- 2013
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 133:8, s. 1840-1845
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Tidskriftsartikel (refereegranskat)abstract
- Genital high-risk human papillomaviruses (HPVs) cause cervical cancer and are also found in a small proportion of nonmelanoma skin cancers (NMSCs). We used cancer registry linkages to follow the 856,000 serum donors included in the Southern Sweden Microbiology Biobank or the Janus Biobank in Norway, for incident skin cancers occurring up to 30 years after serum donation. Serum samples taken before diagnosis of squamous cell carcinoma (SCC) (N = 633), basal cell carcinoma (BCC) (N = 1990) or other NMSC (N = 153) and matched samples from control donors were tested for antibodies to the genital HPV types 16 and 18. Both HPV 16 and 18 were associated with increased risk for SCC [odds ratio (OR) 1.6, 95% confidence interval (CI) 1.1-2.6 and OR 1.7, 95% CI 1.1-2.5, respectively] and other NMSC (OR 2.3, 95% CI 1.0-5.2 and OR 3.5, 95% CI 1.4-8.7, respectively), but not for BCC. Tumor blocks from HPV16 or 18 seropositive cases were tested with real-time polymerase chain reaction for presence of HPV16 or 18 DNA. No HPV18 DNA was found and only four of 79 SCC cases (two of which were from the perineum/perianal area), one of 221 BCC cases and zero of five cases with other NMSC contained HPV16 DNA. In conclusion, we found prospective evidence that HPV16 and 18 antibodies associate with SCC and other NMSC risk, but not with BCC risk. As only a small proportion of seropositive subjects had evidence of the corresponding HPV DNA in the tumor, most of this excess risk is likely to be due to confounders associated with genital HPV infection.
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| 17. |
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| 18. |
- Araghi, Marzieh, et al.
(författare)
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Use of moist oral snuff (snus) and pancreatic cancer : Pooled analysis of nine prospective observational studies
- 2017
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 141:4, s. 687-693
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Tidskriftsartikel (refereegranskat)abstract
- While smoking is a well-established risk factor for pancreatic cancer, the effect of smokeless tobacco is less well understood. We used pooled individual data from the Swedish Collaboration on Health Effects of Snus Use to assess the association between Swedish snus use and the risk of pancreatic cancer. A total of 424,152 male participants from nine cohort studies were followed up for risk of pancreatic cancer through linkage to health registers. We used shared frailty models with random effects at the study level, to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for confounding factors. During 9,276,054 person-years of observation, 1,447 men developed pancreatic cancer. Compared to never-snus use, current snus use was not associated with risk of pancreatic cancer (HR 0.96, 95% CI 0.83-1.11) after adjustment for smoking. Swedish snus use does not appear to be implicated in the development of pancreatic cancer in men. Tobacco smoke constituents other than nicotine or its metabolites may account for the relationship between smoking and pancreatic cancer. What's new? While smoking is a well-established risk factor for pancreatic cancer, the effect of smokeless tobacco is less well understood. Smokeless tobacco like snus yields lower exposure to tobacco carcinogens compared with smoking, because it does not undergo combustion, but delivers an equivalent dose of nicotine. Using pooled individual data from the Swedish Collaboration on Health Effects of Snus Use, here the authors show that Swedish snus use does not appear to be implicated in the development of pancreatic cancer in men. Tobacco smoke constituents other than nicotine or its metabolites may account for the relationship between smoking and pancreatic cancer.
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| 19. |
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| 20. |
- Arne, Gabriella, et al.
(författare)
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Expression profiling of GIST: CD133 is associated with KIT exon 11 mutations, gastric location, and poor prognosis.
- 2011
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Ingår i: International journal of cancer. Journal international du cancer. - : Wiley. - 1097-0215 .- 0020-7136. ; 129:5, s. 1149-1161
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Tidskriftsartikel (refereegranskat)abstract
- In gastrointestinal stromal tumors (GISTs), KIT exon 11 deletions are associated with poor prognosis. The aim of this study was to determine the gene expression profiles of GISTs carrying KIT exon 11 deletions and to identify genes associated with poor prognosis. Expression profiling was performed on 9 tumors with KIT exon 11 deletions and 7 without KIT exon 11 mutations using oligonucleotide microarrays. In addition, gene expression profiles for 35 GISTs were analyzed by meta-analysis. Expression of CD133 (prominin-1) protein was examined by tissue microarray (TMA) analysis of 204 GISTs from a population-based study in western Sweden. Survival analysis was performed on patients subjected to R0 resection (n=180) using the Cox proportional hazards model. Gene expression profiling, meta-analysis, and qPCR showed up regulation of CD133 in GISTs carrying KIT exon 11 deletions. Immunohistochemical analysis on TMA confirmed CD133 expression in 28% of all tumors. CD133 positivity was more frequent in gastric GISTs (48%) than in small intestinal GISTs (4%). CD133 positivity was also more frequent in GISTs with KIT exon 11 mutations (41%) than in tumors with mutations in KIT exon 9, PDGFRA, or wild-type tumors (0-17%). Univariate survival analysis showed a significant correlation between the presence of CD133 protein and shorter overall survival (hazard ratio=2.23, P=0.027). Multivariate analysis showed that CD133 provided additional information on patient survival compared to age, sex, NIH risk group and mutational status. CD133 is expressed in a subset of predominantly gastric GISTs with KIT exon 11 mutations and poor prognosis.
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| 21. |
- Arthur, R., et al.
(författare)
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Serum inflammatory markers in relation to prostate cancer severity and death in the Swedish AMORIS study
- 2018
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Ingår i: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 142:11, s. 2254-2262
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation is a well-documented driver of cancer development and progression. However, little is known about its role in prostate carcinogenesis. Thus, we examined the association of C-reactive protein (CRP), haptoglobin, albumin and white blood cells (WBC) with prostate cancer (PCa) severity (defined by PCa risk category and clinicopathological characteristics) and progression (defined by PCa death). We selected 8,471 Swedish men with newly diagnosed PCa who had exposure measurements taken approximately 14 years prior to diagnosis. We calculated odds ratio (OR) and 95% confidence interval (CI) for the associations between the inflammatory markers and PCa severity using logistic regression, while Cox proportional hazard regression was used for the associations with overall and PCa death. Serum CRP levels were associated with increased odds of high risk and metastatic PCa, and high PSA levels (20 mu g/L) (OR: 1.29; 95% CI: 1.06-1.56, 1.32; 1.05-1.65 and 1.51; 1.26-1.81, respectively). Similarly, higher haptoglobin levels were associated with increased odds of metastatic PCa, high PSA level and possibly high grade PCa (1.38; 1.10-1.74, 1.50; 1.17-1.93 and 1.25; 1.00-1.56, respectively). Albumin was positively associated with Gleason 4+3 tumour (1.38; 1.02-1.86) and overall death (HRunit increase in log: 1.60; 95% CI: 1.11-2.30), but inversely associated with high risk PCa and high PSA levels (20 mu g/L) (0.71; 0.56-0.89 and 0.72; 0.5 9-0.90). WBC was associated with increased odds of T3-T4 PCa. Except for albumin, none of these markers were associated with PCa death or overall death. Systemic inflammation as early as 14 years prior to diagnosis may influence prostate cancer severity. What's new? High levels of C-reactive protein can presage a particularly malignant prostate cancer, new results show. Cancers certainly arise in the wake of chronic inflammation, but it's not known exactly how markers of inflammation initiate prostate cancer. Here, the authors show that systemic inflammation can worsen the severity of the cancer, even if it occurred long before the cancer's onset. High levels of CRP and haptoglobin, they found, were associated with prostate cancer with high PSA and metastasis. The question remains whether inflammation pushes cancer cells into a more malignant mode, or selects for the more dangerous cells early on.
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| 22. |
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| 23. |
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| 24. |
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| 25. |
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| 26. |
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| 27. |
- Azerkan, Fatima, et al.
(författare)
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Cervical screening participation and risk among Swedish-born and immigrant women in Sweden
- 2012
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 130:4, s. 937-947
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Tidskriftsartikel (refereegranskat)abstract
- Cervical cancer is one of the most common cancers among women worldwide, although cervical screening has reduced the incidence in many high-income countries. Low screening uptake among immigrant women may reflect differences in risk of cervical cancer. We investigated the degree of participation in cervical screening among immigrant and Swedish-born women and their concurrent risk of cervical cancer based on individual information on Pap smears taken both from organized and opportunistic screening. Mean degree of participation in cervical screening was estimated for women between 23 and 60 years from 1993 to 2005, stratified by birth region and age at migration. In Poisson regression models, we estimated relative risks (RRs), incidence rates and incidence rate ratios of cervical cancer for women adhering or not to the cervical screening program. We also assessed effect of adherence to screening on the risk of cervical cancer among immigrant groups compared to Swedish-born women. The degree of participation was 62% and 49% among Swedish-born and immigrant women, respectively, with large variations between immigrant groups. Participation was lowest among those immigrating at older ages. Swedish-born and immigrant women who where nonadherent to the cervical screening program had a fivefold excess risk of cervical cancer compared to adherent women. After adjustment for screening adherence, excess RRs of cervical cancer were statistically significant only for women from Norway and the Baltic States. Participation to screening is lower among immigrant than Swedish-born women, and adherence to the recommended screening intervals strongly prevents cervical cancer.
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| 28. |
- Babaei, Masoud, et al.
(författare)
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Administration of adjuvant chemotherapy for stage II-III colon cancer patients : An European population-based study
- 2018
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Ingår i: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 142:7, s. 1480-1489
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Tidskriftsartikel (refereegranskat)abstract
- The advantage of adjuvant chemotherapy (ACT) for treating Stage III colon cancer patients is well established and widely accepted. However, many patients with Stage III colon cancer do not receive ACT. Moreover, there are controversies around the effectiveness of ACT for Stage II patients. We investigated the administration of ACT and its association with overall survival in resected Stage II (overall and stratified by low-/high-risk) and Stage III colon cancer patients in three European countries including The Netherlands (2009-2014), Belgium (2009-2013) and Sweden (2009-2014). Hazard ratios (HR) for death were obtained by Cox regression models adjusted for potential confounders. A total of 60244 resected colon cancer patients with pathological Stages II and III were analyzed. A small proportion (range 9-24%) of Stage II and over half (range 55-68%) of Stage III patients received ACT. Administration of ACT in Stages II and III tumors decreased with higher age of patients. Administration of ACT was significantly associated with higher overall survival in high-risk Stage II patients (in The Netherlands (HR; 95%CI = 0.82 (0.67-0.99), Belgium (0.73; 0.59-0.90) and Sweden (0.58; 0.44-0.75)), and in Stage III patients (in The Netherlands (0.47; 0.43-0.50), Belgium (0.46; 0.41-0.50) and Sweden (0.48; 0.43-0.54)). In Stage III, results were consistent across subgroups including elderly patients. Our results show an association of ACT with higher survival among Stage III and high-risk Stage II colon cancer patients. Further investigations are needed on the selection criteria of Stages II and III colon cancer patients for ACT.
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| 29. |
- Baglietto, Laura, et al.
(författare)
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DNA methylation changes measured in pre-diagnostic peripheral blood samples are associated with smoking and lung cancer risk
- 2017
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 140:1, s. 50-61
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Tidskriftsartikel (refereegranskat)abstract
- DNA methylation changes are associated with cigarette smoking. We used the Illumina Infinium HumanMethylation450 array to determine whether methylation in DNA from pre-diagnostic, peripheral blood samples is associated with lung cancer risk. We used a case-control study nested within the EPIC-Italy cohort and a study within the MCCS cohort as discovery sets (a total of 552 case-control pairs). We validated the top signals in 429 case-control pairs from another 3 studies. We identified six CpGs for which hypomethylation was associated with lung cancer risk: cg05575921 in the AHRR gene (p-valuepooled = 4 × 10(-17) ), cg03636183 in the F2RL3 gene (p-valuepooled = 2 × 10 (- 13) ), cg21566642 and cg05951221 in 2q37.1 (p-valuepooled = 7 × 10(-16) and 1 × 10(-11) respectively), cg06126421 in 6p21.33 (p-valuepooled = 2 × 10(-15) ) and cg23387569 in 12q14.1 (p-valuepooled = 5 × 10(-7) ). For cg05951221 and cg23387569 the strength of association was virtually identical in never and current smokers. For all these CpGs except for cg23387569, the methylation levels were different across smoking categories in controls (p-valuesheterogeneity ≤ 1.8 x10 (- 7) ), were lowest for current smokers and increased with time since quitting for former smokers. We observed a gain in discrimination between cases and controls measured by the area under the ROC curve of at least 8% (p-values ≥ 0.003) in former smokers by adding methylation at the 6 CpGs into risk prediction models including smoking status and number of pack-years. Our findings provide convincing evidence that smoking and possibly other factors lead to DNA methylation changes measurable in peripheral blood that may improve prediction of lung cancer risk.
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| 30. |
- Baltzer, Nicholas, et al.
(författare)
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Risk stratification in cervical cancer screening by complete screening history : Applying bioinformatics to a general screening population
- 2017
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 141:1, s. 200-209
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Tidskriftsartikel (refereegranskat)abstract
- Women screened for cervical cancer in Sweden are currently treated under a one-size-fits-all programme, which has been successful in reducing the incidence of cervical cancer but does not use all of the participants' available medical information. This study aimed to use women's complete cervical screening histories to identify diagnostic patterns that may indicate an increased risk of developing cervical cancer. A nationwide case-control study was performed where cervical cancer screening data from 125,476 women with a maximum follow-up of 10 years were evaluated for patterns of SNOMED diagnoses. The cancer development risk was estimated for a number of different screening history patterns and expressed as Odds Ratios (OR), with a history of 4 benign cervical tests as reference, using logistic regression. The overall performance of the model was moderate (64% accuracy, 71% area under curve) with 61-62% of the study population showing no specific patterns associated with risk. However, predictions for high-risk groups as defined by screening history patterns were highly discriminatory with ORs ranging from 8 to 36. The model for computing risk performed consistently across different screening history lengths, and several patterns predicted cancer outcomes. The results show the presence of risk-increasing and risk-decreasing factors in the screening history. Thus it is feasible to identify subgroups based on their complete screening histories. Several high-risk subgroups identified might benefit from an increased screening density. Some low-risk subgroups identified could likely have a moderately reduced screening density without additional risk.
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| 31. |
- Bamia, Christina, et al.
(författare)
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Coffee, tea and decaffeinated coffee in relation to hepatocellular carcinoma in a European population: Multicentre, prospective cohort study
- 2015
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 136, s. 1899-1908
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Tidskriftsartikel (refereegranskat)abstract
- © 2014 UICC. Inverse associations of coffee and/or tea in relation to hepatocellular carcinoma (HCC) risk have been consistently identified in studies conducted mostly in Asia where consumption patterns of such beverages differ from Europe. In the European Prospective Investigation into Cancer and nutrition (EPIC), we identified 201 HCC cases among 486,799 men/women, after a median follow-up of 11 years. We calculated adjusted hazard ratios (HRs) for HCC incidence in relation to quintiles/categories of coffee/tea intakes. We found that increased coffee and tea intakes were consistently associated with lower HCC risk. The inverse associations were substantial, monotonic and statistically significant. Coffee consumers in the highest compared to the lowest quintile had lower HCC risk by 72% [HR: 0.28; 95% confidence intervals (CIs): 0.16-0.50, p-trend < 0.001]. The corresponding association of tea with HCC risk was 0.41 (95% CI: 0.22-0.78, p-trend50.003). There was no compelling evidence of heterogeneity of these associations across strata of important HCC risk factors, including hepatitis B or hepatitis C status (available in a nested case-control study). The inverse, monotonic associations of coffee intake with HCC were apparent for caffeinated (p-trend50.009), but not decaffeinated (p-trend50.45) coffee for which, however, data were available for a fraction of subjects. Results from this multicentre, European cohort study strengthen the existing evidence regarding the inverse association between coffee/tea and HCC risk. Given the apparent lack of heterogeneity of these associations by HCC risk factors and that coffee/tea are universal exposures, our results could have important implications for high HCC risk subjects.
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| 32. |
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| 33. |
- Bao, Cuiping, et al.
(författare)
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Diabetes in midlife and risk of cancer in late life : A nationwide Swedish twin study
- 2018
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 143:4, s. 793-800
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Tidskriftsartikel (refereegranskat)abstract
- The association between diabetes and cancer risk remains controversial. Hence, we examined whether midlife diabetes is related to the risk of cancer in late-life, and whether genetic and early-life environmental factors play a role in this association. This study included 25,154 twin individuals born in 1958 or earlier from the Swedish Twin Registry. Information on cancer diagnosis in late life (aged >= 65) during 1998-2014, was derived from the National Patient and Cancer Registries. Diabetes was ascertained based on self- or informant-reported history, patient registry and antidiabetic medication use. Midlife diabetes was defined when diabetes was diagnosed before 65 years. Data were analyzed following two strategies: (i) unmatched case-control analysis for all participants using generalized estimating equation (GEE) models, and (ii) co-twin control analysis for cancer-discordant twin pairs using conditional logistic regression. Overall, 1,766 (7.0%) had midlife diabetes and 5,293 (21.0%) had cancer in late-life. In multiadjusted GEE models, the odds ratios (95% CIs) of diabetes were 10.55 (2.95-37.67) for pharynx cancer, 5.78 (1.72-19.40) for small intestine cancer, 2.37 (1.14-4.91) for liver cancer and 0.48 (0.35-0.67) for prostate cancer. In people with diabetes, diabetes duration was dose-dependently associated with cancer risk. In conditional logistic regression analysis of 176 prostate cancer-discordant twin pairs, the association between midlife diabetes and prostate cancer in later life became stronger. Midlife diabetes increases the risk of pharynx, small intestine and liver cancers, but reduces prostate cancer risk in late life. Genetic and early-life environmental factors may partially contribute to the diabetes-prostate cancer association.
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| 34. |
- Bao, Cuiping, et al.
(författare)
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Overweight in midlife and risk of cancer in late life : A nationwide Swedish twin study
- 2019
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 144:9, s. 2128-2134
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Tidskriftsartikel (refereegranskat)abstract
- Our study examined whether midlife overweight (body mass index [BMI] >= 25) is associated with late-life cancer risk and explored the role of genetic and early-life environmental factors in this association. The study included 14,766 individuals from the Swedish Twin Registry, whose midlife (30-50 years) height and weight were recorded. Information on cancer diagnoses in late life (>65 years) was derived from the National Patient Registry and Cancer Registry. Generalized estimating equation (GEE) models were used to analyze unmatched case-control data (controlled for the clustering of twins within a pair). A co-twin matched case-control analysis used conditional logistic regression to compare cancer-discordant twins. Of all participants, 3968 (26.9%) were overweight and 4253 (28.8%) had cancer. In multi-adjusted GEE models using normal-weight (BMI 18.5-24.9) participants as the reference group, overweight was related to higher risk of colon cancer (OR 1.36, 95% CI: 1.00-1.84, p = 0.049), liver cancer (OR 2.00, 95% CI: 1.11-3.62), cervix uteri cancer (OR 2.86, 95% CI: 1.19-6.91) and corpus uteri cancer (OR 1.78, 95% CI: 1.14-2.78) but lower risk of nonmelanoma skin cancer (OR 0.77, 95% CI: 0.66-0.90). In conditional logistic regression analysis, these associations were attenuated becoming nonsignificance. The difference in ORs from the unmatched and matched analyses was not significant. In conclusion, midlife overweight is associated with increased risk of late-life colon, liver and uterine cancer but reduced risk of late-life nonmelanoma skin cancer. Further investigations are warranted to explore the role of genetic and early-life environmental factors in these associations.
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| 35. |
- Barash, Uri, et al.
(författare)
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Heparanase promotes glioma progression via enhancing CD24 expression
- 2019
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Ingår i: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 145:6, s. 1596-1608
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Tidskriftsartikel (refereegranskat)abstract
- Heparanase is an endo-beta-d-glucuronidase that cleaves heparan sulfate (HS) side chains of heparan sulfate proteoglycans. Compelling evidence tie heparanase levels with all steps of tumor formation including tumor initiation, growth, metastasis and chemo-resistance, likely involving augmentation of signaling pathways and gene transcription. In order to reveal the molecular mechanism(s) underlying the protumorigenic properties of heparanase, we established an inducible (Tet-on) system in U87 human glioma cells and applied gene array methodology in order to identify genes associated with heparanase induction. We found that CD24, a mucin-like cell adhesion protein, is consistently upregulated by heparanase and by heparanase splice variant devoid of enzymatic activity, whereas heparanase gene silencing was associated with decreased CD24 expression. This finding was further substantiated by a similar pattern of heparanase and CD24 immunostaining in glioma patients (Pearson's correlation; R = 0.66, p = 0.00001). Noteworthy, overexpression of CD24 stimulated glioma cell migration, invasion, colony formation in soft agar and tumor growth in mice suggesting that CD24 functions promote tumor growth. Likewise, anti-CD24 neutralizing monoclonal antibody attenuated glioma tumor growth, and a similar inhibition was observed in mice treated with a neutralizing mAb directed against L1 cell adhesion molecule (L1CAM), a ligand for CD24. Importantly, significant shorter patient survival was found in heparanase-high/CD24-high tumors vs. heparanase-high/CD24-low tumors for both high-grade and low-grade glioma (p = 0.02). Our results thus uncover a novel heparanase-CD24-L1CAM axis that plays a significant role in glioma tumorigenesis.
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| 36. |
- Barrdahl, Myrto, et al.
(författare)
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A comprehensive analysis of polymorphic variants in steroid hormone and insulin-like growth factor-1 metabolism and risk of in situ breast cancer : Results from the Breast and Prostate Cancer Cohort Consortium
- 2018
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 142:6, s. 1182-1188
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Tidskriftsartikel (refereegranskat)abstract
- We assessed the association between 1,414 single nucleotide polymorphisms (SNPs) in genes involved in synthesis and metabolism of steroid hormones and insulin-like growth factor 1, and risk of breast cancer in situ (BCIS), with the aim of determining whether any of these were disease specific. This was carried out using 1,062 BCIS cases and 10,126 controls as well as 6,113 invasive breast cancer cases from the Breast and Prostate Cancer Cohort Consortium (BPC3). Three SNPs showed at least one nominally significant association in homozygous minor versus homozygous major models. ACVR2A-rs2382112 (ORhom=3.05, 95%CI=1.72-5.44, Phom=1.47 × 10-4), MAST2-rs12124649 (ORhom=1.73, 95% CI =1.18-2.54, Phom=5.24 × 10-3), and INSR-rs10500204 (ORhom=1.96, 95% CI=1.44-2.67, Phom=1.68 × 10-5) were associated with increased risk of BCIS; however, only the latter association was significant after correcting for multiple testing. Furthermore, INSR-rs10500204 was more strongly associated with the risk of BCIS than invasive disease in case-only analyses using the homozygous minor versus homozygous major model (ORhom=1.78, 95% CI=1.30-2.44, Phom=3.23 × 10-4). The SNP INSR-rs10500204 is located in an intron of the INSR gene and is likely to affect binding of the promyelocytic leukemia (PML) protein. The PML gene is known as a tumor suppressor and growth regulator in cancer. However, it is not clear on what pathway the A-allele of rs10500204 could operate to influence the binding of the protein. Hence, functional studies are warranted to investigate this further.
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| 37. |
- Barrdahl, Myrto, et al.
(författare)
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Association of breast cancer risk loci with breast cancer survival
- 2015
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Ingår i: International Journal of Cancer. - : Wiley-Blackwell. - 0020-7136 .- 1097-0215. ; 137:12, s. 2837-2845
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Tidskriftsartikel (refereegranskat)abstract
- The survival of breast cancer patients is largely influenced by tumor characteristics, such as TNM stage, tumor grade and hormone receptor status. However, there is growing evidence that inherited genetic variation might affect the disease prognosis and response to treatment. Several lines of evidence suggest that alleles influencing breast cancer risk might also be associated with breast cancer survival. We examined the associations between 35 breast cancer susceptibility loci and the disease over-all survival (OS) in 10,255 breast cancer patients from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) of which 1,379 died, including 754 of breast cancer. We also conducted a meta-analysis of almost 35,000 patients and 5,000 deaths, combining results from BPC3 and the Breast Cancer Association Consortium (BCAC) and performed in silico analyses of SNPs with significant associations. In BPC3, the C allele of LSP1-rs3817198 was significantly associated with improved OS (HRper-allele=0.70; 95% CI: 0.58-0.85; ptrend=2.84 x 10-4; HRheterozygotes=0.71; 95% CI: 0.55-0.92; HRhomozygotes=0.48; 95% CI: 0.31-0.76; p2DF=1.45 x 10-3). In silico, the C allele of LSP1-rs3817198 was predicted to increase expression of the tumor suppressor cyclin-dependent kinase inhibitor 1C (CDKN1C). In the meta-analysis, TNRC9-rs3803662 was significantly associated with increased death hazard (HRMETA =1.09; 95% CI: 1.04-1.15; ptrend=6.6 x 10-4; HRheterozygotes=0.96 95% CI: 0.90-1.03; HRhomozygotes=1.21; 95% CI: 1.09-1.35; p2DF=1.25 x 10-4). In conclusion, we show that there is little overlap between the breast cancer risk single nucleotide polymorphisms (SNPs) identified so far and the SNPs associated with breast cancer prognosis, with the possible exceptions of LSP1-rs3817198 and TNRC9-rs3803662.What's new? Genetic factors are known to influence the risk of breast cancer, but inherited genetic variation may also affect disease prognosis and response to treatment. In this study, the we investigated whether single nucleotide polymorphisms (SNPs) that are known to be associated with breast cancer risk might also influence the survival of breast-cancer patients. While two of the investigated SNPs may influence survival, there was otherwise no indication that SNP alleles related to breast cancer risk also play a role in the survival of breast cancer patients.
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| 38. |
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| 39. |
- Barrett, Jennifer H., et al.
(författare)
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Fine mapping of genetic susceptibility loci for melanoma reveals a mixture of single variant and multiple variant regions
- 2015
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 136:6, s. 1351-1360
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Tidskriftsartikel (refereegranskat)abstract
- At least 17 genomic regions are established as harboring melanoma susceptibility variants, in most instances with genome-wide levels of significance and replication in independent samples. Based on genome-wide single nucleotide polymorphism (SNP) data augmented by imputation to the 1,000 Genomes reference panel, we have fine mapped these regions in over 5,000 individuals with melanoma (mainly from the GenoMEL consortium) and over 7,000 ethnically matched controls. A penalized regression approach was used to discover those SNP markers that most parsimoniously explain the observed association in each genomic region. For the majority of the regions, the signal is best explained by a single SNP, which sometimes, as in the tyrosinase region, is a known functional variant. However in five regions the explanation is more complex. At the CDKN2A locus, for example, there is strong evidence that not only multiple SNPs but also multiple genes are involved. Our results illustrate the variability in the biology underlying genome-wide susceptibility loci and make steps toward accounting for some of the missing heritability. What's new? In genome-wide association studies, researchers identify genetic variants that frequently associate with a particular disease, though the variants identified may not contribute to the molecular cause of the disease. This study took a closer look at 17 regions associated with melanoma, fine mapping the regions both in people with melanoma and in healthy controls. Though single SNPs account for the association in some regions, they found that in a few regions, several SNPs - and possibly multiple genes - contributed to the association signal. These findings illustrate the importance of not overlooking the interaction between multiple genetic markers when conducting such studies.
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| 40. |
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| 41. |
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| 42. |
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| 43. |
- Basu, P, et al.
(författare)
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Erratum
- 2018
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Ingår i: International journal of cancer. - : Wiley. - 1097-0215 .- 0020-7136. ; 143:1, s. E1-E1
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Tidskriftsartikel (refereegranskat)
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| 44. |
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| 45. |
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| 46. |
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| 47. |
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| 48. |
- Berntsson, Jonna, et al.
(författare)
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Prognostic impact of tumour-infiltrating B cells and plasma cells in colorectal cancer
- 2016
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 139:5, s. 1129-1139
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Tidskriftsartikel (refereegranskat)abstract
- Multiple studies have described associations between infiltrating immune cells and prognosis in cancer; however, the clinical relevance has most often been attributed to the T-cell linage. This study aimed to further investigate the clinicopathological correlates and prognostic impact of B cell and plasma cell infiltration in CRC. Immunohistochemical expression of CD20, CD138 and immunoglobulin kappa C (IGKC) was analysed in tissue microarrays with tumours from 557 incident cases of CRC from a prospective population-based cohort. Kaplan-Meier analysis and Cox regression analysis were used to determine the impact of CD20, CD138 and IGKC expression on 5-year overall survival. Immune cell-specific CD20, CD138, and IGKC expression correlated significantly with lower T-stage (p < 0.001, p < 0.001, and p=0.006, respectively). A higher density of CD201 cells correlated significantly with an improved OS (HR=0.53, 95% CI 0.36-0.78), remaining significant in multivariable analysis adjusted for age, TNM stage, differentiation grade and vascular invasion (HR=0.51; 95% CI 0.33-0.80). Immune cell-specific CD138 and IGKC expression correlated significantly with an improved OS in univariable Cox regression analysis; however, these associations did not remain significant in multivariable analysis. Finally, tumour cell-specific CD138 expression was found to be an independent factor of poor prognosis (HR 1.52; 95% CI 1.03-2.24). The results from the present study demonstrate that B cell infiltration in CRC has a significant impact on tumour progression and prognosis. These findings supplement and extend the current knowledge of the immune landscape in colorectal cancer, and merit further study.
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| 49. |
- Berntsson, Jonna, et al.
(författare)
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The clinical impact of tumour-infiltrating lymphocytes in colorectal cancer differs by anatomical subsite : A cohort study
- 2017
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Ingår i: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 141:8, s. 1654-1666
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Tidskriftsartikel (refereegranskat)abstract
- Accumulating evidence demonstrates an association between dense infiltration of lymphocytes and prognosis in colorectal cancer (CRC), but whether this prognostic impact differs by tumour location remains unknown. This study investigated the prognostic impact of cytotoxic and regulatory T cells in CRC, with particular referennfiltrating T cce to the anatomical subsite of the primary tumour. The density of CD3(+), CD8(+) and FoxP3(+) tumour-iells was calculated in tissue microarrays with tumours from 557 incident CRC cases from a prospective population-based cohort. Kaplan-Meier and Cox regression analyses were applied to determine the impact of high and low lymphocyte density on 5-year overall survival, in subgroup analysis of right colon, left colon and rectum. High CD8(+) cell density was a favourable prognostic factor for patients with right-sided colon tumours (hazard ratio [HR]=0.53, 95% confidence interval [CI] 0.29-0.95), independent of age, sex, TNM stage, differentiation grade and vascular invasion, with a significant prognostic interaction between CD8(+) cells and right-sidedness (p=0.031). High FoxP3(+) cell density was an independent favourable prognostic factor only in patients with rectal tumours (HR=0.54, 95% CI 0.30-0.99), and CD3(+) cell density was an independent favourable prognostic factor for tumours in the right colon and rectum, but there was no significant prognostic interaction between CD3(+) or FoxP3(+) cells and sidedness. These results demonstrate that the prognostic impact of tumour-infiltrating lymphocytes in CRC differs by primary tumour site, further indicating that tumour location may be an important factor to take into consideration in therapeutic decisions, including eligibility for immunotherapy.
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| 50. |
- Bogen, D., et al.
(författare)
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The genetic tumor background is an important determinant for heterogeneous MYCN-amplified neuroblastoma
- 2016
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 139:1, s. 153-163
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Tidskriftsartikel (refereegranskat)abstract
- Amplification of MYCN is the signature genetic aberration of 20-25% of neuroblastoma and a stratifying marker associated with aggressive tumor behavior. The detection of heterogeneous MYCN amplification (hetMNA) poses a diagnostic dilemma due to the uncertainty of its relevance to tumor behavior. Here, we aimed to shed light on the genomic background which permits hetMNA in neuroblastoma and tied the occurrence to other stratifying markers and disease outcome. We performed SNP analysis using Affymetrix Cytoscan HD arrays on 63 samples including constitutional DNA, tumor, bone marrow and relapse samples of 26 patients with confirmed hetMNA by MYCN-FISH. Tumors of patients 18m were mostly aneuploid with numeric chromosomal aberrations (NCAs), presented a prominent MNA subclone and carried none or a few segmental chromosomal aberrations (SCAs). In older patients, tumors were mostly di- or tetraploid, contained a lower number of MNA cells and displayed a multitude of SCAs including concomitant 11q deletions. These patients often suffered disease progression, tumor dissemination and relapse. Restricted to aneuploid tumors, we detected chromosomes with uniparental di- or trisomy (UPD/UPT) in almost every sample. UPD11 was exclusive to tumors of younger patients whereas older patients featured UPD14. In this study, the MNA subclone appears to be constraint by the tumor environment and thus less relevant for tumor behavior in aggressive tumors with a high genomic instability and many segmental aberrations. A more benign tumor background and lower tumor stage may favor an outgrowth of the MNA clone but tumors generally responded better to treatment. What's new?MYCN amplification (MNA) in neuroblastoma (NB) generally associates with an aggressive tumor behavior and detection of MNA leads to an automatic upstaging of the tumor in non-stage 1 tumors. But what if only a fraction of the tumor cells is MYCN-amplified? To investigate the diagnostic importance of heterogeneous MNA, the authors conducted a genetic analysis of samples from 26 NB patients with a particular focus on accompanying genetic aberrations. They concluded that tumor behavior is largely dependent on patient age and other chromosomal alterations in the genetic tumor background rather than the mere presence of the MNA clone.
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