| 1. |
- Ding, Yuan C, et al.
(författare)
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A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers
- 2012
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 21:8, s. 1362-1370
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers.METHODS: IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers.RESULTS: Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06-1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39-3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28-2.70; class I HR, 0.86; 95%CI, 0.69-1.09; P(difference), 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03).CONCLUSION: The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers.Impact: These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers.
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| 3. |
- Davidsson, Sabina, et al.
(författare)
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Inflammation, Focal Atrophic Lesions, and Prostatic Intraepithelial Neoplasia with Respect to Risk of Lethal Prostate Cancer
- 2011
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 20:10, s. 2280-2287
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Tidskriftsartikel (refereegranskat)abstract
- Background: A challenge in prostate cancer (PCa) management is identifying potentially lethal disease at diagnosis. Inflammation, focal prostatic atrophy, and prostatic intraepithelial neoplasia (PIN) are common in prostate tumor specimens, but it is not clear whether these lesions have prognostic significance. less thanbrgreater than less thanbrgreater thanMethods: We conducted a case-control study nested in a cohort of men diagnosed with stage T1a-b PCa through transurethral resection of the prostate in Sweden. Cases are men who died of PCa (n = 228). Controls are men who survived more than 10 years after PCa diagnosis without metastases (n = 387). Slides were assessed for Gleason grade, inflammation, PIN, and four subtypes of focal prostatic atrophy: simple atrophy (SA), postatrophic hyperplasia (PAH), simple atrophy with cyst formation, and partial atrophy. We estimated OR and 95% CI for odds of lethal PCa with multivariable logistic regression. less thanbrgreater than less thanbrgreater thanResults: Chronic inflammation and PIN were more frequently observed in tumors with PAH, but not SA. No specific type of atrophy or inflammation was significantly associated with lethal PCa overall, but there was a suggestion of a positive association for chronic inflammation. Independent of age, Gleason score, year of diagnosis, inflammation, and atrophy type, men with PIN were 89% more likely to die of PCa (95% CI: 1.04-3.42). less thanbrgreater than less thanbrgreater thanConclusion: Our data show that PIN, and perhaps presence of moderate or severe chronic inflammation, may have prognostic significance for PCa. less thanbrgreater than less thanbrgreater thanImpact: Lesions in tumor adjacent tissue, and not just the tumor itself, may aid in identification of clinically relevant disease.
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| 4. |
- Hedelin, Maria, 1964, et al.
(författare)
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Dietary Phytoestrogens and the Risk of Ovarian Cancer in the Womens Lifestyle and Health Cohort Study
- 2011
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Ingår i: CANCER EPIDEMIOLOGY BIOMARKERS and PREVENTION. - : American Association for Cancer Research Inc. - 1055-9965. ; 20:2, s. 308-317:20, s. 308-317
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dietary intake of phytoestrogens has been inversely associated to hormone-dependent cancers, such as prostate and breast cancers. Few studies have investigated the association between ovarian cancer and intake of phytoestrogens. We evaluated the associations between intake of phytoestrogens (isoflavonoids/lignans/coumestrol) and fiber (vegetable/cereal) and risk of ovarian cancer. Methods: In 1991-1992 a prospective population-based cohort study among Swedish women was conducted, including 47,140 women with complete dietary questionnaire data. During follow-up until December 2007, 163 women developed invasive (n = 117) and borderline (n = 46) ovarian cancers. The median follow-up time was 16 years and total person year was 747,178. Cox proportional hazards models were conducted to estimate multivariate risk ratios, 95% CI for associations with risk of ovarian cancer. Results: We found no association between intake of phytoestrogens or fiber and overall ovarian cancer risk. In addition, we found no statistically significant association between intake of specific food items rich in phytoestrogens (berries, nuts, beans/soy, and crisp or whole-grain bread) and ovarian cancer risk overall. Fiber and coumestrol was inversely associated with borderline ovarian cancer, but not with invasive ovarian cancer. Conclusions: We found no association between intake of phytoestrogens or fiber and overall ovarian cancer risk. Impact: Phytoestrogens do not play a major etiologic role in ovarian cancer, at least among women in this Swedish cohort with low bean/soy intake. However, our results of a difference in the effect of fiber or coumestrol between invasive and borderline ovarian cancer need to be evaluated in larger studies.
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| 5. |
- Kuper, Hannah, et al.
(författare)
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Prospective Study of Solar Exposure, Dietary Vitamin D Intake, and Risk of Breast Cancer among Middle-aged Women
- 2009
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - Philadelphia, Pennsylvania : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 18:9, s. 2558-2561
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The relationship between solar exposure or dietary vitamin D intake and breast cancer risk has not been fully elucidated. These associations were studied within the Womens Lifestyle and Health Cohort Study, a cohort of 49,259 Swedish women ages 30 to 50 years at baseline (1991-1992). Women were asked about solar exposure and completed a food frequency questionnaire and were followed-up through linkages to national registries until December 2004. In the current analyses, 41,889 women were included, 840 of whom were diagnosed with breast cancer during follow-up. Breast cancer risk was not related to solar exposure variables, including sun sensitivity, annual number of sunburns, time spent on sunbathing vacations, or solarium use at any age period of exposure. There was also no association with dietary vitamin D intake or supplementary multivitamin use. These relationships were not modified after stratifying by estrogen or progesterone receptor status.
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| 6. |
- Wiechec, Emilia, et al.
(författare)
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High-Resolution Melting Analysis for Mutation Screening of RGSL1, RGS16, and RGS8 in Breast Cancer
- 2011
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 20:2, s. 397-407
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Tidskriftsartikel (refereegranskat)abstract
- Background: Identification of specific mutation targets in cancer may lead to discovery of the genes modulating cancer susceptibility and/or prognosis. The RGSL1, RGS16, and RGS8 genes within the 1q25.3 region belong to the novel family of regulators of G protein signaling (RGS) genes, which increase the GTPase activity of the G alpha subunit to attenuate signaling from the G protein-coupled receptor. We evaluated the use of high-resolution melting (HRM) to screen for mutations in the genes of interest and assess their clinical significance. Methods: The HRM analysis was used to screen 32 coding exons of RGSL1, RGS16, and RGS8 in tumors from 200 breast cancer patients. All sequence variants detected by HRM resulted in abnormal shape of the melting curves. The identified mutations and known single nucleotide polymorphisms (SNP) were subsequently confirmed by sequencing, and distribution of the SNP genotypes was determined by SNaPshot analysis. A case-control analysis of genotype frequencies was carried out. Results: We identified three tumor specific missense mutations in RGSL1 (ex6 c.664 G>A (Val222Ile), ex13 c.2262 C>G (Asp754Glu), and ex13 c.2316 C>T (Ser772Leu) in three different breast cancer patients. In addition, a total of seven known SNPs were identified in this study. Genotype distributions were not significantly different between breast cancer patients and controls. Conclusions and Impact: Identification of novel mutations within RGSL1 provides a new insight into the pathophysiology of breast cancer. Moreover, the HRM analysis represents a reliable and highly sensitive method for mutation scanning of multiple exons.
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| 7. |
- Yang, Ling, et al.
(författare)
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Prospective Study of UV Exposure and Cancer Incidence Among Swedish Women
- 2011
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research Inc. - 1055-9965 .- 1538-7755. ; 20:7, s. 1358-1367
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Tidskriftsartikel (refereegranskat)abstract
- Background: Except for skin melanoma and nonmelanoma skin cancer, little evidence from prospective studies is available on the association between UV exposure and cancer risk. Methods: We followed prospectively 49,261 women aged 30 to 49 years at enrollment in 1991 to 1992 for 15 years. Cancer incidence was analyzed by fitting Cox models, and estimating hazard ratios (HR) and 95% confidence intervals (CI). Results: 2,303 incident cases of cancer were diagnosed (breast: 1,053, ovary: 126, lung: 116, colon-rectum: 133, and brain: 116). No associations were found between any cumulative measure of UV exposure at ages 10 to 39 years and overall cancer risk. However, spending greater than= 1 week/year between ages 10 and 29 years on sunbathing vacations led to an inverse association with overall cancer risk (HR: 0.70, 95% CI: 0.53-0.93) and breast cancer risk (HR: 0.56, 95% CI: 0.36-0.89) when compared with women who never went on such vacations. Solarium use was inversely associated with breast cancer risk, whereas greater than= 2 sunburns/year was inversely associated with lung cancer risk. No other associations were found between sun exposure or solarium use at ages 10 to 39 years and cancer risk. Conclusion: We found no evidence of an association between any cumulative measure of UV exposure at ages 10 to 39 years and overall cancer risk. UV exposure earlier in life was related to reduced overall and breast cancer risk. Impact: Further research is needed to define the amount of solar or artificial UV exposure that may, or may not, be beneficial for cancer prevention.
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| 8. |
- Mustafa, Tarek, et al.
(författare)
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Expression of the epidermal growth factor seven-transmembrane member CD97 correlates with grading and staging in human oral squamous cell carcinomas
- 2005
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 14:1, s. 108-119
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The oral squamous cell carcinoma (OSCC) is the sixth most common malignant tumor worldwide. No significant better progress has been made in the treatment of OSCCs during the last decades. The heterodimeric CD97 protein is a epidermal growth factor seven-transmembrane family member and was identified as a dedifferentiation marker in thyroid carcinomas. Nothing is known about CD97 in OSCCs. Material andMETHODS: Employing UV-laser microdissection, CD97 and its ligand CD55 were investigated in normal oral mucosa and OSCCs (n = 78) by multiplex reverse transcription-PCR. Frozen sections were investigated by immunohistochemistry. The effects of retinoic acid and sodium butyrate on the CD97/CD55 expression in OSCC cell lines were determined by quantitative PCR, immunocytochemistry, and flow cytometry.RESULTS: Weak CD97 transcripts were expressed in normal mucosa and normal basal epithelial cells revealed specific CD97 immunostaining. Strong CD97 transcripts were detected in pT(3)/T(4) and G3/G4 OSCC tissues, whereas pT(1)/T(2) and G1/G2 carcinomas revealed weak CD97 transcript levels. A weak CD97 immunostaining was observed in pT(1)/T(2) and G1/G2 tumors. By contrast, intensive CD97 immunostaining was detected in pT(3)/T(4) OSCCs and G3/G4 lesions. CD55 gene expression was low in normal mucosa. All OSCCs, irrespective of stage and grading, displayed strong CD55 immunostaining. Sodium butyrate and retinoic acid inhibited CD97 mRNA and protein in OSCC cell lines. Interestingly, CD55 was up-regulated by both substances.CONCLUSION: We identified CD97 as a novel marker of dedifferentiated OSCC. Interaction of CD97 and CD55 may facilitate adhesion of OSCC cells to surrounding surfaces that would result in metastases and bad prognosis.
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| 9. |
- Yngveson, A, et al.
(författare)
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p53 Mutations in lung cancer associated with residential radon exposure.
- 1999
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 8:5
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Tidskriftsartikel (refereegranskat)abstract
- Unusual mutation patterns in lung tumors among underground miners have been indicated, suggesting radon-specific alterations in the genome, but the data are not consistent. To investigate the association between residential radon exposure and p53 mutations in lung tumors, we performed a study on cases from a nation-wide population-based investigation in Sweden. Our study included 83 nonsmoking lung cancer cases and 250 smoking lung cancer cases, diagnosed 1980-1984, with a time-weighted average radon exposure over 140 Bq/m3 or up to 50 Bq/m3. Radon was measured in dwellings occupied by the study subjects at some time since 1947. Information on smoking habits and other risk factors was obtained from questionnaires. After exclusions because of the initiation of treatment or insufficient material, the p53-status of 243 tumors was determined using PCR-single-stranded conformation polymorphism analysis and sequencing determination of exons 5-8. The overall mutation prevalence was 23.9%. An increased mutation prevalence was suggested among those with high exposure to residential radon [odds ratio (OR), 1.4; 95% CI, 0.7-2.6], especially among nonsmokers (OR, 3.2; 95% CI, 0.7-15.5), but no specific mutational pattern was indicated. Furthermore, the mutation prevalence seemed to be higher among smoking lung cancer cases than among nonsmoking cases (OR, 2.1; 95% CI, 0.9-5.0), and particularly among those smoking less than 10 cigarettes per day. It may be concluded that residential exposure to radon seems to contribute to a higher mutation prevalence of the p53 gene in lung tumors.
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