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1.
  • Couto, E, et al. (författare)
  • Mediterranean dietary pattern and cancer risk in the EPIC cohort.
  • 2011
  • Ingår i: British Journal of Cancer. - Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 104:9, s. 1493-1499
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>BACKGROUND:</strong> Although several studies have investigated the association of the Mediterranean diet with overall mortality or risk of specific cancers, data on overall cancer risk are sparse.</p> <p><strong>METHODS:</strong> We examined the association between adherence to Mediterranean dietary pattern and overall cancer risk using data from the European Prospective Investigation Into Cancer and nutrition, a multi-centre prospective cohort study including 142,605 men and 335,873. Adherence to Mediterranean diet was examined using a score (range: 0-9) considering the combined intake of fruits and nuts, vegetables, legumes, cereals, lipids, fish, dairy products, meat products, and alcohol. Association with cancer incidence was assessed through Cox regression modelling, controlling for potential confounders.</p> <p><strong>RESULTS:</strong> In all, 9669 incident cancers in men and 21,062 in women were identified. A lower overall cancer risk was found among individuals with greater adherence to Mediterranean diet (hazard ratio=0.96, 95% CI 0.95-0.98) for a two-point increment of the Mediterranean diet score. The apparent inverse association was stronger for smoking-related cancers than for cancers not known to be related to tobacco (P (heterogeneity)=0.008). In all, 4.7% of cancers among men and 2.4% in women would be avoided in this population if study subjects had a greater adherence to Mediterranean dietary pattern.</p> <p><strong>CONCLUSION:</strong> Greater adherence to a Mediterranean dietary pattern could reduce overall cancer risk.</p>
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2.
  • Discacciati, A., et al. (författare)
  • Body mass index in early and middle-late adulthood and risk of localised, advanced and fatal prostate cancer : a population-based prospective study
  • 2011
  • Ingår i: British Journal of Cancer. - Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 105:7, s. 1061-1068
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>BACKGROUND</strong>: The relationships between body mass index (BMI) during early and middle-late adulthood and incidence of prostate cancer (PCa) by subtype of the disease (localised, advanced) and fatal PCa is unclear.</p><p><strong>METHODS</strong>: A population-based cohort of 36,959 Swedish men aged 45-79 years was followed up from January 1998 through December 2008 for incidence of PCa (1530 localised and 554 advanced cases were diagnosed) and through December 2007 for PCa mortality (225 fatal cases).</p><p><strong>RESULTS</strong>: From a competing-risks analysis, incidence of localised PCa was observed to be inversely associated with BMI at baseline (middle-late adulthood; rate ratio (RR) for 35 kg m(-2) when compared with 22 kg m(-2) was 0.69 (95% CI 0.52-0.92)), but not at age 30. For fatal PCa, BMI at baseline was associated with a nonstatistically significant increased risk (RR for every five-unit increase: 1.12 (0.88-1.43)) and BMI at age 30 with a decreased risk (RR for every five-unit increase: 0.72 (0.51-1.01)).</p><p><strong>CONCLUSION</strong>: Our results indicate an inverse association between obesity during middle-late, but not early adulthood, and localised PCa. They also suggest a dual association between BMI and fatal PCa--a decreased risk among men who were obese during early adulthood and an increased risk among those who were obese during middle-late adulthood.</p>
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3.
  • Elsir, T., et al. (författare)
  • PROX1 is a predictor of survival for gliomas WHO grade II
  • 2011
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 104:11, s. 1747-1754
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Background:The clinical course of World Health Organisation grade II gliomas remains variable and their time point of transformation into a more malignant phenotype is unpredictable. Identification of biological markers that can predict prognosis in individual patients is of great clinical value. PROX1 is a transcription factor that has a critical role in the development of various organs. PROX1 has been ascribed both oncogenic and tumour suppressive functions in human cancers. We have recently shown that PROX1 may act as a diagnostic marker for high-grade gliomas. The aim of this study was to address the prognostic value of PROX1 in grade II gliomas.Methods:A total of 116 samples were evaluated for the presence of PROX1 protein. The number of immunopositive cells was used as a variable in survival analysis, together with established prognostic factors for this patient group.Results:Higher PROX1 protein was associated with poor outcome. In the multivariate analysis, PROX1 was identified as an independent factor for survival (P=0.024), together with the presence of mutated isocitrate dehydrogenase 1 R132H protein, and with combined losses of chromosomal arms 1p/19q in oligodendrocytic tumours.Conclusion:PROX1 is a novel predictor of survival for grade II gliomas.</p>
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4.
  • Gremel, G., et al. (författare)
  • Functional and prognostic relevance of the homeobox protein MSX2 in malignant melanoma
  • 2011
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 105:4, s. 565-574
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>BACKGROUND: The homeobox containing transcription factor MSX2 is a key regulator of embryonic development and has been implicated to have a role in breast and pancreatic cancer. METHODS: Using a selection of two-and three-dimensional in vitro assays and tissue microarrays (TMAs), the clinical and functional relevance of MSX2 in malignant melanoma was explored. A doxycyline-inducible over-expression system was applied to study the relevance of MSX2 in vitro. For TMA construction, tumour material from 218 melanoma patients was used. RESULTS: Ectopic expression of MSX2 resulted in the induction of apoptosis and reduced the invasive capacity of melanoma cells in three-dimensional culture. MSX2 over-expression was shown to affect several signalling pathways associated with cell invasion and survival. Downregulation of N-Cadherin, induction of p21 and inhibition of both BCL2 and Survivin were observed. Cytoplasmic MSX2 expression was found to correlate significantly with increased recurrence-free survival (P = 0.008). Nuclear expression of MSX2 did not result in significant survival correlations, suggesting that the beneficial effect of MSX2 may be independent of its DNA binding activity. CONCLUSIONS: MSX2 may be an important regulator of melanoma cell invasion and survival. Cytoplasmic expression of the protein was identified as biomarker for good prognosis in malignant melanoma patients.</p>
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5.
  • Gyllensten, Ulf, et al. (författare)
  • Short-time repeat high-risk HPV testing by self-sampling for screening of cervical cancer
  • 2011
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 105:5, s. 694-697
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>BACKGROUND: Testing for high-risk human papillomavirus (HPV) in primary screening for cervical cancer is considered more sensitive, but less specific, in comparison with Pap-smear cytology. Women with persistent HPV infections have a higher risk of developing cervical intraepithelial neoplasia 2+ (CIN2+) lesions. This study was performed to evaluate the gain in specificity for detection of histologically confirmed CIN2+ lesions achieved by short-time repeat testing for high-risk HPV in women aged 30-65 years, with the primary sample for HPV analysis taken by self-sampling. METHODS: A total of 8000 women in Uppsala County, aged 30-65 years, who had not attended organised screening for 6 years or longer, were offered self-sampling of vaginal fluid at home and the samples sent for HPV typing. Of these, 8% (669) were not possible to contact or had performed hysterectomy. Women positive for high-risk HPV in the self-sampling test were invited for a follow-up HPV test and a cervical biopsy on average 3 months after the initial HPV test. RESULTS: In all, 39% (2850/7331) of invited women chose to perform self-sampling of vaginal fluid at home. High-risk HPV infection was found in 6.6% (188) of the women. In all, 89% of the women testing HPV positive performed a follow-up examination, on average 2.7 months, after the first test and 59% of these women were HPV positive in the follow-up test. The prevalence of CIN2+ lesions in women with an initial HPV-positive test was 23% (95% CI 18-30%) and in women with two consecutive HPV-positive tests was 41% (95% CI 31-51%). In women with two positive HPV tests, the prevalence of CIN2+ lesions varied from 49% in women at age 30-39 years to 24% in women at age 50-65 years. Short-time repeat HPV testing increased the specificity for detection of CIN2+ lesions from about 94.2% to 97.8%. The most prevalent HPV types were HPV16 (32%), followed by HPV18/45 (19%) and HPV 33/52/58 (19%). CONCLUSION: The short-time persistence of high-risk HPV infection in this age group was about 60%. Repeat testing for high-risk HPV using self-sampling of vaginal fluid can be used to increase the specificity in the screening for cervical cancer in women aged 30-65 years.</p>
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6.
  • Jerevall, Piiha-Lotta, et al. (författare)
  • Prognostic utility of HOXB13:IL17BR and Molecular Grade Index in early-stage breast cancer patients from the Stockholm trial
  • 2011
  • Ingår i: British Journal of Cancer. - Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 104:11, s. 1762-1769
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>Background:</strong> A dichotomous index combining two gene expression assays, HOXB13:IL17BR (H:I) and molecular grade index (MGI), was developed to assess risk of recurrence in breast cancer patients. The study objective was to demonstrate the prognostic utility of the combined index in early-stage breast cancer.</p> <p><strong>Methods:</strong> In a blinded retrospective analysis of 588 ER-positive tamoxifen-treated and untreated breast cancer patients from the randomized prospective Stockholm trial, H:I and MGI were measured using real-time RT-PCR. Association with patient outcome was evaluated by Kaplan-Meier analysis and Cox proportional hazard regression. A continuous risk index was developed using Cox modeling.</p> <p><strong>Results:</strong> The dichotomous H:I+MGI was significantly associated with distant recurrence and breast cancer death. The &gt;50% of tamoxifen-treated patients categorized as low-risk had &lt;3% 10-year distant recurrence risk. A continuous risk model (Breast Cancer Index (BCI)) was developed with the tamoxifen-treated group and the prognostic performance tested in the untreated group was 53% of patients categorized as low-risk with an 8.3% 10-year distant recurrence risk.</p> <p><strong>Conclusion:</strong> Retrospective analysis of this randomized, prospective trial cohort validated the prognostic utility of H:I+MGI and was used to develop and test a continuous risk model that enables prediction of distant recurrence risk at the patient level.</p>
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7.
  • Key, T J, et al. (författare)
  • Circulating sex hormones and breast cancer risk factors in postmenopausal women : reanalysis of 13 studies.
  • 2011
  • Ingår i: British Journal of Cancer. - Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 105:5, s. 709-722
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>BACKGROUND:</strong> Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood.</p> <p><strong>METHODS:</strong> Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies.</p> <p><strong>RESULTS:</strong> Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer.</p> <p><strong>CONCLUSION:</strong> Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk.</p>
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8.
  • Larsson, A., et al. (författare)
  • Overexpression of podocalyxin-like protein is an independent factor of poor prognosis in colorectal cancer
  • 2011
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 105:5, s. 666-672
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>BACKGROUND: Podocalyxin-like 1 (PODXL) is a cell-adhesion glycoprotein and stem cell marker that has been associated with an aggressive tumour phenotype and poor prognosis in several forms of cancer. In this study, we investigated the prognostic impact of PODXL expression in colorectal cancer (CRC). METHODS: Using tissue microarrays and immunohistochemistry, PODXL expression was evaluated in 536 incident CRC cases from a prospective, population-based cohort study. Kaplan-Meier analysis and Cox proportional hazards modelling were used to assess the impact of PODXL expression on cancer-specific survival (CSS) and overall survival (OS). RESULTS: High PODXL expression was significantly associated with unfavourable clinicopathological characteristics, a shorter CSS (hazard ratio (HR) = 1.98; 95% confidence interval (CI) 1.38-2.84, P &lt; 0.001) and 5-year OS (HR = 1.85; 95% CI 1.29-2.64, P = 0.001); the latter remaining significant in multivariate analysis (HR = 1.52; 95% CI 1.03-2.25, P = 0.036). In addition, in curatively resected stage III (T1-4, N1-2, M0) patients (n = 122) with tumours with high PODXL expression, a significant benefit from adjuvant chemotherapy was demonstrated (p(interaction) = 0.004 for CSS and 0.015 for 5-year OS in multivariate analysis). CONCLUSION: Podocalyxin-like 1 expression is an independent factor of poor prognosis in CRC. Our results also suggest that PODXL may be a useful marker to stratify patients for adjuvant chemotherapy.</p>
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9.
  • Lee, C.K., et al. (författare)
  • Prognostic nomogram to predict progression-free survival in patients with platinum-sensitive recurrent ovarian cancer
  • 2011
  • Ingår i: British Journal of Cancer. - Cancer Research UK. - 0007-0920 .- 1532-1827. ; 105:8, s. 1144-1150
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>BACKGROUND: Patients with platinum-sensitive recurrent ovarian cancer are a heterogeneous group, and it is not possible to accurately predict the progression-free survival (PFS) in these patients. We developed and validated a nomogram to help improve prediction of PFS in patients treated with platinum-based chemotherapy. METHODS: The nomogram was developed in a training cohort (n = 955) from the CALYPSO trial and validated in the AGO-OVAR 2.5 Study (n = 340). The proportional-hazards model (nomogram) was based on pre-treatment characteristics. RESULTS: The nomogram had a concordance index (C-index) of 0.645. Significant predictors were tumour size platinum-chemotherapy-free interval, CA-125, number of organ metastatic sites and white blood count. When the nomogram was applied without CA-125 (CA-125 was not available in validation cohort), the C-indices were 0.624 (training) and 0.594 (validation). When classification was based only on the platinum-chemotherapy-free interval, the indices were 0.571 (training) and 0.560 (validation). The calibration plot in the validation cohort based on four predictors (without CA-125) suggested good agreement between actual and nomogram-predicted 12-month PFS probabilities. CONCLUSION: This nomogram, using five pre-treatment characteristics, improves prediction of PFS in patients with platinum-sensitive ovarian cancer having platinum-based chemotherapy. It will be useful for the design and stratification of patients in clinical trials and also for counselling patients. </p>
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10.
  • Lind, H, et al. (författare)
  • Late symptoms in long-term gynaecological cancer survivors after radiation therapy : a population-based cohort study.
  • 2011
  • Ingår i: British Journal of Cancer. - Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 105:6, s. 737-745
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>BACKGROUND:</strong> We surveyed the occurrence of physical symptoms among long-term gynaecological cancer survivors after pelvic radiation therapy, and compared with population-based control women.</p><p><strong>METHODS:</strong> We identified a cohort of 789 eligible gynaecological cancer survivors treated with pelvic radiation therapy alone or combined with surgery in Stockholm or Gothenburg, Sweden. A control group of 478 women was randomly sampled from the Swedish Population Registry. Data were collected through a study-specific validated postal questionnaire with 351 questions concerning gastrointestinal and urinary tract function, lymph oedema, pelvic bones and sexuality. Clinical characteristics and treatment details were retrieved from medical records.</p><p><strong>RESULTS:</strong> Participation rate was 78% for gynaecological cancer survivors and 72% for control women. Median follow-up time after treatment was 74 months. Cancer survivors reported a higher occurrence of symptoms from all organs studied. The highest age-adjusted relative risk (RR) was found for emptying of all stools into clothing without forewarning (RR 12.7), defaecation urgency (RR 5.7), difficulty feeling the need to empty the bladder (RR 2.8), protracted genital pain (RR 5.0), pubic pain when walking indoors (RR 4.9) and erysipelas on abdomen or legs at least once during the past 6 months (RR 3.6). Survivors treated with radiation therapy alone showed in general higher rates of symptoms.</p><p><strong>CONCLUSION:</strong> Gynaecological cancer survivors previously treated with pelvic radiation report a higher occurrence of symptoms from the urinary and gastrointestinal tract as well as lymph oedema, sexual dysfunction and pelvic pain compared with non-irradiated control women. Health-care providers need to actively ask patients about specific symptoms in order to provide proper diagnostic investigations and management.</p>
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