1.
Sampson, Joshua N., et al.
(författare)
Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
2015
Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
Tidskriftsartikel (refereegranskat) abstract
Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
2.
Emaus, Marleen J., et al.
(författare)
Vegetable and fruit consumption and the risk of hormone receptor-defined breast cancer in the EPIC cohort
2016
Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 103:1, s. 168-177
Tidskriftsartikel (refereegranskat) abstract
Background: The recent literature indicates that a high vegetable intake and not a high fruit intake could be associated with decreased steroid hormone receptor–negative breast cancer risk.Objective: This study aimed to investigate the association between vegetable and fruit intake and steroid hormone receptor–defined breast cancer risk.Design: A total of 335,054 female participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort were included in this study (mean ± SD age: 50.8 ± 9.8 y). Vegetable and fruit intake was measured by country-specific questionnaires filled out at recruitment between 1992 and 2000 with the use of standardized procedures. Cox proportional hazards models were stratified by age at recruitment and study center and were adjusted for breast cancer risk factors.Results: After a median follow-up of 11.5 y (IQR: 10.1–12.3 y), 10,197 incident invasive breast cancers were diagnosed [3479 estrogen and progesterone receptor positive (ER+PR+); 1021 ER and PR negative (ER−PR−)]. Compared with the lowest quintile, the highest quintile of vegetable intake was associated with a lower risk of overall breast cancer (HRquintile 5–quintile 1: 0.87; 95% CI: 0.80, 0.94). Although the inverse association was most apparent for ER−PR− breast cancer (ER−PR−: HRquintile 5–quintile 1: 0.74; 95% CI: 0.57, 0.96; P-trend = 0.03; ER+PR+: HRquintile 5–quintile 1: 0.91; 95% CI: 0.79, 1.05; P-trend = 0.14), the test for heterogeneity by hormone receptor status was not significant (P-heterogeneity = 0.09). Fruit intake was not significantly associated with total and hormone receptor–defined breast cancer risk.Conclusion: This study supports evidence that a high vegetable intake is associated with lower (mainly hormone receptor–negative) breast cancer risk.
3.
Besevic, Jelena, et al.
(författare)
Reproductive factors and epithelial ovarian cancer survival in the EPIC cohort study
2015
Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 113:11, s. 1622-1631
Tidskriftsartikel (refereegranskat) abstract
Background: Reproductive factors influence the risk of developing epithelial ovarian cancer (EOC), but little is known about their association with survival. We tested whether prediagnostic reproductive factors influenced EOC-specific survival among 1025 invasive EOC cases identified in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, which included 521 330 total participants (approximately 370 000 women) aged 25-70 years at recruitment from 1992 to 2000. Methods: Information on reproductive characteristics was collected at recruitment. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), and multivariable models were adjusted for age and year of diagnosis, body mass index, tumour stage, smoking status and stratified by study centre. Results: After a mean follow-up of 3.6 years (+/- 3.2 s.d.) following EOC diagnosis, 511 (49.9%) of the 1025 women died from EOC. We observed a suggestive survival advantage in menopausal hormone therapy (MHT) users (ever vs never use, HR = 0.80, 95% CI = 0.62-1.03) and a significant survival benefit in long-term MHT users (>= 5 years use vs never use, HR = 0.70, 95% CI = 0.50-0.99, P-trend = 0.04). We observed similar results for MHT use when restricting to serous cases. Other reproductive factors, including parity, breastfeeding, oral contraceptive use and age at menarche or menopause, were not associated with EOC-specific mortality risk. Conclusions: Further studies are warranted to investigate the possible improvement in EOC survival in MHT users.
4.
Fortner, Renee T., et al.
(författare)
Correlates of circulating ovarian cancer early detection markers and their contribution to discrimination of early detection models : results from the EPIC cohort
2017
Ingår i: Journal of Ovarian Research. - : Springer Science and Business Media LLC. - 1757-2215. ; 10
Tidskriftsartikel (refereegranskat) abstract
Background: Ovarian cancer early detection markers CA125, CA15.3, HE4, and CA72.4 vary between healthy women, limiting their utility for screening.Methods: We evaluated cross-sectional relationships between lifestyle and reproductive factors and these markers among controls (n = 1910) from a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC). Improvements in discrimination of prediction models adjusting for correlates of the markers were evaluated among postmenopausal women in the nested case-control study (n = 590 cases). Generalized linear models were used to calculate geometric means of CA125, CA15.3, and HE4. CA72.4 above vs. below limit of detection was evaluated using logistic regression. Early detection prediction was modeled using conditional logistic regression.Results: CA125 concentrations were lower, and CA15.3 higher, in post- vs. premenopausal women (p ≤ 0.02). Among postmenopausal women, CA125 was higher among women with higher parity and older age at menopause (ptrend ≤ 0.02), but lower among women reporting oophorectomy, hysterectomy, ever use of estrogen-only hormone therapy, or current smoking (p < 0.01). CA15.3 concentrations were higher among heavier women and in former smokers (p ≤ 0.03). HE4 was higher with older age at blood collection and in current smokers, and inversely associated with OC use duration, parity, and older age at menopause (≤ 0.02). No associations were observed with CA72.4. Adjusting for correlates of the markers in prediction models did not improve the discrimination.Conclusions: This study provides insights into sources of variation in ovarian cancer early detection markers in healthy women and informs about the utility of individualizing marker cutpoints based on epidemiologic factors.
5.
Vergnaud, Anne-Claire, et al.
(författare)
Adherence to the World Cancer Research Fund/American Institute for Cancer Research guidelines and risk of death in Europe : results from the European Prospective Investigation into Nutrition and Cancer cohort study
2013
Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 97:5, s. 1107-1120
Tidskriftsartikel (refereegranskat) abstract
Background: In 2007, the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) issued recommendations on diet, physical activity, and weight management for cancer prevention on the basis of the most comprehensive collection of available evidence. Objective: We investigated whether concordance with WCRF/AICR recommendations is related to risk of death. Design: The current study included 378,864 participants from 9 European countries enrolled in the European Prospective Investigation into Cancer and Nutrition study. At recruitment (1992-1998), dietary, anthropometric, and lifestyle information was collected. A WCRF/AICR score, which incorporated 6 of the WCRF/AICR recommendations for men [regarding body fatness, physical activity, foods and drinks that promote weight gain, plant foods, animal foods, and alcoholic drinks (score range: 0-6)] and 7 WCRF/AICR recommendations for women [plus breastfeeding (score range: 0-7)], was constructed. Higher scores indicated greater concordance with WCRF/AICR recommendations. Associations between the WCRF/AICR score and risks of total and cause-specific death were estimated by using Cox regression analysis. Results: After a median follow-up time of 12.8 y, 23,828 deaths were identified. Participants within the highest category of the WCRF/AICR score (5-6 points in men; 6-7 points in women) had a 34% lower hazard of death (95% CI: 0.59, 0.75) compared with participants within the lowest category of the WCRF/AICR score (0-2 points in men; 0-3 points in women). Significant inverse associations were observed in all countries. The WCRF/AICR score was also significantly associated with a lower hazard of dying from cancer, circulatory disease, and respiratory disease. Conclusion: Results of this study suggest that following WCRF/AICR recommendations could significantly increase longevity.
6.
Vrieling, Alina, et al.
(författare)
One-carbon metabolism biomarkers and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition
2019
Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 145:9, s. 2349-2359
Tidskriftsartikel (refereegranskat) abstract
Published associations between dietary folate and bladder cancer risk are inconsistent. Biomarkers may provide more accurate measures of nutrient status. This nested case-control analysis within the European Prospective Investigation into Cancer and Nutrition (EPIC) investigated associations between pre-diagnostic serum folate, homocysteine, vitamins B6 and B12 and the risk of urothelial cell carcinomas of the bladder (UCC). A total of 824 patients with newly diagnosed UCC were matched with 824 cohort members. Serum folate, homocysteine, and vitamins B6 and B12 were measured. Odds ratios (OR) and 95% confidence intervals (CI) for total, aggressive, and non-aggressive UCC were estimated using conditional logistic regression with adjustment for smoking status, smoking duration and intensity, and other potential confounders. Additionally, statistical interaction with smoking status was assessed. A halving in serum folate concentrations was moderately associated with risk of UCC (OR: 1.18; 95% CI: 0.98-1.43), in particular aggressive UCC (OR: 1.34; 95% CI: 1.02-1.75; p-heterogeneity = 0.19). Compared to never smokers in the highest quartile of folate concentrations, this association seemed only apparent among current smokers in the lowest quartile of folate concentrations (OR: 6.26; 95% CI: 3.62-10.81, p-interaction = 0.07). Dietary folate was not associated with aggressive UCC (OR: 1.26; 95% CI: 0.81-1.95; p-heterogeneity = 0.14). No association was observed between serum homocysteine, vitamins B6 and B12 and risk of UCC. This study suggests that lower serum folate concentrations are associated with increased UCC risk, in particular aggressive UCC. Residual confounding by smoking cannot be ruled out and these findings require confirmation in future studies with multiple measurements.
7.
Dik, Vincent K., et al.
(författare)
Coffee and tea consumption, genotype- based CYP1A2 and NAT2 activity and colorectal cancer risk- Results from the EPIC cohort study
2014
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 135:2, s. 401-412
Tidskriftsartikel (refereegranskat) abstract
Coffee and tea contain numerous antimutagenic and antioxidant components and high levels of caffeine that may protect against colorectal cancer (CRC). We investigated the association between coffee and tea consumption and CRC risk and studied potential effect modification by CYP1A2 and NAT2 genotypes, enzymes involved in the metabolization of caffeine. Data from 477,071 participants (70.2% female) of the European Investigation into Cancer and Nutrition (EPIC) cohort study were analyzed. At baseline (1992-2000) habitual (total, caffeinated and decaffeinated) coffee and tea consumption was assessed with dietary questionnaires. Cox proportional hazards models were used to estimate adjusted hazard ratio's (HR) and 95% confidence intervals (95% CI). Potential effect modification by genotype-based CYP1A2 and NAT2 activity was studied in a nested case-control set of 1,252 cases and 2,175 controls. After a median follow-up of 11.6 years, 4,234 participants developed CRC (mean age 64.78.3 years). Total coffee consumption (high vs. non/low) was not associated with CRC risk (HR 1.06, 95% CI 0.95-1.18) or subsite cancers, and no significant associations were found for caffeinated (HR 1.10, 95% CI 0.97-1.26) and decaffeinated coffee (HR 0.96, 95% CI 0.84-1.11) and tea (HR 0.97, 95% CI 0.86-1.09). High coffee and tea consuming subjects with slow CYP1A2 or NAT2 activity had a similar CRC risk compared to non/low coffee and tea consuming subjects with a fast CYP1A2 or NAT2 activity, which suggests that caffeine metabolism does not affect the link between coffee and tea consumption and CRC risk. This study shows that coffee and tea consumption is not likely to be associated with overall CRC. What's new? Coffee and tea contain numerous compounds that may protect against colorectal cancer (CRC). In this study of more than 475,000 participants over more than a decade, the authors investigated whether coffee or tea consumption is associated with an altered risk of developing CRC. They also asked whether genetic variations in two enzymes involved in caffeine metabolism (CYP1A2 and NAT2) might affect this risk. They conclude that neither consumption patterns, nor genetic differences in caffeine metabolism, appear to have a significant impact on CRC risk.
8.
Dik, Vincent K, et al.
(författare)
Prediagnostic intake of dairy products and dietary calcium and colorectal cancer survival - results from the EPIC cohort study.
2014
Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755 .- 1055-9965. ; 23:9, s. 1813-1823
Tidskriftsartikel (refereegranskat) abstract
Background We investigated whether prediagnostic reported intake of dairy products and dietary calcium are associated with colorectal cancer (CRC) survival. Methods Data from 3,859 subjects with CRC (42.1% male, mean age at diagnosis 64.2 ± 8.1 years) in the European Investigation into Cancer and Nutrition (EPIC) cohort were analyzed. Intake of dairy products and dietary calcium was assessed at baseline (1992-2000) using validated, country-specific dietary questionnaires. Multivariable Cox regression models were used to calculate hazard ratios (HR) and corresponding 95% confidence intervals (95%-CI) for CRC specific death (n=1,028) and all-cause death (n=1,525) for different quartiles of intake. Results The consumption of total dairy products was not statistically significantly associated with risk of CRC-specific death (adjusted HR Q4 vs. Q1: 1.17 95%-CI 0.97-1.43) nor of all-cause death (Q4 vs. Q1: 1.16 95%-CI 0.98-1.36). Multivariable adjusted HRs for CRC-specific death (Q4 vs. Q1) were 1.21 (95%-CI 0.99-1.48) for milk, 1.09 (95%-CI 0.88-1.34) for yoghurt and 0.93 (95%-CI 0.76-1.14) for cheese. The intake of dietary calcium was not associated with the risk of CRC-specific (adjusted HR Q4 vs. Q1: 1.01 95%-CI 0.81-1.26) nor of all-cause death (Q4 vs. Q1: 1.01 95%-CI 0.84-1.21). Conclusions The prediagnostic reported intake of dairy products and dietary calcium are not associated with disease-specific or all-cause risk of death in patients diagnosed with CRC. Impact The impact of diet on cancer survival is largely unknown. This study shows that despite it's inverse association with CRC risk, the prediagnostic intake of dairy and dietary calcium do not affect CRC survival.
9.
Fedirko, Veronika, et al.
(författare)
Pre-diagnostic anthropometry and survival after colorectal cancer diagnosis in Western European populations
2014
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 135:8, s. 1949-1960
Tidskriftsartikel (refereegranskat) abstract
General and abdominal adiposity are associated with a high risk of developing colorectal cancer (CRC), but the role of these exposures on cancer survival has been less studied. The association between pre-diagnostic anthropometric characteristics and CRC-specific and all-cause death was examined among 3,924 men and women diagnosed with CRC between 1992 and 2009 in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Multivariable Cox proportional hazards models were used to calculate hazard ratios (FIRS) and corresponding 95% confidence intervals (as). Over a mean follow-up period of 49 months, 1,309 deaths occurred of which 1,043 (79.7%) were due to CRC. In multivariable analysis, prediagnostic BMI kg/m2 was associated with a high risk for CRC-specific (HR = 1.26, 95% CI = 1.04-1.52) and all-cause (HR = 1.32, 95% CI = 1.12-1.56) death relative to BMI <25 kg/m(2). Every 5 kg/m(2) increase in BMI was associated with a high risk for CRC-specific (HR = 1.10, 95% CI = 1.02-1.19) and all-cause death (HR = 1.12, 95% Cl = 1.05-1.20); and every 10 cm increase in waist circumference was associated with a high risk for CRC-specific (HR = 1.09, 95% Cl = 1.02-1.16) and allcause death (HR= 1.11, 95% CI= 1.05-1.18). Similar associations were observed for waist-to-hip and waist-to-height ratios. Height was not associated with CRC-specific or all-cause death. Associations tended to be stronger among men than in women. Possible interactions by age at diagnosis, cancer stage, tumour location, and hormone replacement therapy use among postmenopausal women were noted. Pre-diagnostic general and abdominal adiposity are associated with lower survival after CRC diagnosis.
10.
Kaaks, Rudolf, et al.
(författare)
Risk factors for cancers of unknown primary site: Results from the prospective EPIC cohort
2014
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 135:10, s. 2475-2481
Tidskriftsartikel (refereegranskat) abstract
Cancer of unknown primary site (CUP) may be called an orphan disease, as it is diagnosed when metastases are detected while the primary tumor typically remains undetected, and because little research has been done on its primary causes. So far, few epidemiological studies, if any, have addressed possible risk factors for CUP. We analyzed data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (N=476,940). During prospective follow-up, a total of 651 cases of incident cases of CUP were detected (ICD-O-2 code C809). Proportional hazards models were conducted to examine the associations of lifetime history of smoking habits, alcohol consumption, levels of education and anthropometric indices of adiposity with risk of being diagnosed with CUP. Risk of being diagnosed with CUP was strongly related to smoking, with a relative risk of 3.66 [95% C.I., 2.24-5.97] for current, heavy smokers (26+ cigarettes/day) compared to never smokers (adjusted for alcohol consumption, body mass index, waist circumference and level of education) and a relative risk of 5.12 [3.09-8.47] for cases with CUP who died within 12 months. For alcohol consumption and level of education, weaker associations were observed but attenuated and no longer statistically significant after adjusting for smoking and indices of obesity. Finally, risk of CUP was increased by approximately 30 per cent for subjects in the highest versus lowest quartiles of waist circumference. Our analyses provide further documentation, in addition to autopsy studies, that a substantial proportion of cancers of unknown primary site may have their origin in smoking-related tumors, in particular. What's new? When cancer appears as metastatic disease but no primary tumor can be observed, it's called cancer of unknown primary site. Little is known about the risk factors for this type of cancer. This study analyzed data from a European cohort and discovered a strong association between smoking and these cancers. Other risk factors they identified were drinking alcohol and being fat. This is the first epidemiological study of these type of cancers, and it strengthens the observations from autopsy studies that many of these cancers of unknown primary site stem from smoking-related tumors.
