| 1. |
- Huyghe, Jeroen R., et al.
(författare)
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Discovery of common and rare genetic risk variants for colorectal cancer
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:1, s. 76-
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Tidskriftsartikel (refereegranskat)abstract
- To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
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| 2. |
- Rohrmann, S., et al.
(författare)
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Smoking and the risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition
- 2013
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 108:3, s. 708-714
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Tidskriftsartikel (refereegranskat)abstract
- Background: Smoking is not associated with prostate cancer incidence in most studies, but associations between smoking and fatal prostate cancer have been reported. Methods: During 1992 and 2000, lifestyle information was assessed via questionnaires and personal interview in a cohort of 145112 European men. Until 2009, 4623 incident cases of prostate cancer were identified, including 1517 cases of low-grade, 396 cases of high grade, 1516 cases of localised, 808 cases of advanced disease, and 432 fatal cases. Multivariable Cox proportional hazards regression models were used to examine the association of smoking status, smoking intensity, and smoking duration with the risk of incident and fatal prostate cancer. Results: Compared with never smokers, current smokers had a reduced risk of prostate cancer (RR = 0.90, 95% CI: 0.83-0.97), which was statistically significant for localised and low-grade disease, but not for advanced or high-grade disease. In contrast, heavy smokers (25+ cigarettes per day) and men who had smoked for a long time (40+ years) had a higher risk of prostate cancer death (RR = 1.81, 95% CI: 1.11-2.93; RR = 1.38, 95% CI: 1.01-1.87, respectively). Conclusion: The observation of an increased prostate cancer mortality among heavy smokers confirms the results of previous prospective studies.
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| 3. |
- Sieri, Sabina, et al.
(författare)
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Dietary Fat Intake and Development of Specific Breast Cancer Subtypes.
- 2014
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 106:5, s. 068-068
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Tidskriftsartikel (refereegranskat)abstract
- We prospectively evaluated fat intake as predictor of developing breast cancer (BC) subtypes defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 receptor (HER2), in a large (n = 337327) heterogeneous cohort of women, with 10062 BC case patients after 11.5 years, estimating BC hazard ratios (HRs) by Cox proportional hazard modeling. High total and saturated fat were associated with greater risk of ER(+)PR(+) disease (HR = 1.20, 95% confidence interval [CI] = 1.00 to 1.45; HR = 1.28, 95% CI = 1.09 to 1.52; highest vs lowest quintiles) but not ER(-)PR(-) disease. High saturated fat was statistically significantly associated with greater risk of HER2(-) disease. High saturated fat intake particularly increases risk of receptor-positive disease, suggesting saturated fat involvement in the etiology of this BC subtype.
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| 4. |
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| 5. |
- Nitter, M., et al.
(författare)
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Plasma methionine, choline, betaine, and dimethylglycine in relation to colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)
- 2014
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 25:8, s. 1609-1615
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Tidskriftsartikel (refereegranskat)abstract
- Background: Disturbances in one carbon metabolism may contribute to carcinogenesis by affecting methylation and synthesis of DNA. Choline and its oxidation product betaine are involved in this metabolism and can serve as alternative methyl group donors when folate status is low. Patients and methods: We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), to investigate plasma concentrations of the methyl donors methionine, choline, betaine (trimethylglycine), and dimethylglycine (DMG) in relation to colorectal cancer (CRC) risk. Our study included 1367 incident CRC cases (965 colon and 402 rectum) and 2323 controls matched by gender, age group, and study center. Multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for CRC risk were estimated by conditional logistic regression, comparing the fifth to the first quintile of plasma concentrations. Results: Overall, methionine (OR: 0.79, 95% CI: 0.63-0.99, P-trend = 0.05), choline (OR: 0.77, 95% CI: 0.60-0.99, P-trend = 0.07), and betaine (OR: 0.85, 95% CI: 0.66-1.09, P-trend = 0.06) concentrations were inversely associated with CRC risk of borderline significance. In participants with folate concentration below the median of 11.3 nmol/l, high betaine concentration was associated with reduced CRC risk (OR: 0.71, 95% CI: 0.50-1.00, P-trend = 0.02), which was not observed for those having a higher folate status. Among women, but not men, high choline concentration was associated with decreased CRC risk (OR: 0.62, 95% CI: 0.43-0.88, P-trend = 0.01). Plasma DMG was not associated with CRC risk. Conclusions: Individuals with high plasma concentrations of methionine, choline, and betaine may be at reduced risk of CRC.
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| 6. |
- van Duijnhoven, Fraenzel J. B., et al.
(författare)
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Circulating concentrations of vitamin D in relation to pancreatic cancer risk in European populations
- 2018
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Ingår i: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 142:6, s. 1189-1201
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Tidskriftsartikel (refereegranskat)abstract
- Evidence from in vivo, in vitro and ecological studies are suggestive of a protective effect of vitamin D against pancreatic cancer (PC). However, this has not been confirmed by analytical epidemiological studies. We aimed to examine the association between pre-diagnostic circulating vitamin D concentrations and PC incidence in European populations. We conducted a pooled nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nord-TrOndelag Health Study's second survey (HUNT2) cohorts. In total, 738 primary incident PC cases (EPIC n=626; HUNT2 n=112; median follow-up=6.9 years) were matched to 738 controls. Vitamin D [25(OH)D-2 and 25(OH)D-3 combined] concentrations were determined using isotope-dilution liquid chromatography-tandem mass spectrometry. Conditional logistic regression models with adjustments for body mass index and smoking habits were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95%CI). Compared with a reference category of >50 to 75 nmol/L vitamin D, the IRRs (95% CIs) were 0.71 (0.42-1.20); 0.94 (0.72-1.22); 1.12 (0.82-1.53) and 1.26 (0.79-2.01) for clinically pre-defined categories of 25; >25 to 50; >75 to 100; and >100 nmol/L vitamin D, respectively (p for trend=0.09). Corresponding analyses by quintiles of season-standardized vitamin D concentrations also did not reveal associations with PC risk (p for trend=0.23). Although these findings among participants from the largest combination of European cohort studies to date show increasing effect estimates of PC risk with increasing pre-diagnostic concentrations of vitamin D, they are not statistically significant.
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| 7. |
- Trichopoulos, Dimitrios, et al.
(författare)
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Hepatocellular carcinoma risk factors and disease burden in a European cohort : a nested case-control study
- 2011
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Ingår i: Journal of the National Cancer Institute. - Oxford : Oxford University Press. - 0027-8874 .- 1460-2105. ; 103:22, s. 1686-1695
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Tidskriftsartikel (refereegranskat)abstract
- Background: To date, no attempt has been made to systematically determine the apportionment of the hepatocellular carcinoma burden in Europe or North America among established risk factors.Methods: Using data collected from 1992 to 2006, which included 4 409 809 person-years in the European Prospective Investigation into Cancer and nutrition (EPIC), we identified 125 case patients with hepatocellular carcinoma, of whom 115 were matched to 229 control subjects. We calculated odds ratios (ORs) for the association of documented risk factors for hepatocellular carcinoma with incidence of this disease and estimated their importance in this European cohort.Results: Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (OR = 9.10, 95% confidence interval [CI] = 2.10 to 39.50 and OR = 13.36, 95% CI = 4.11 to 43.45, respectively), obesity (OR = 2.13, 95% CI = 1.06 to 4.29), former or current smoking (OR = 1.98, 95% CI = 0.90 to 4.39 and OR = 4.55, 95% CI = 1.90 to 10.91, respectively), and heavy alcohol intake (OR = 1.77, 95% CI = 0.73 to 4.27) were associated with hepatocellular carcinoma. Smoking contributed to almost half of all hepatocellular carcinomas (47.6%), whereas 13.2% and 20.9% were attributable to chronic HBV and HCV infection, respectively. Obesity and heavy alcohol intake contributed 16.1% and 10.2%, respectively. Almost two-thirds (65.7%, 95% CI = 50.6% to 79.3%) of hepatocellular carcinomas can be accounted for by exposure to at least one of these documented risk factors.Conclusions: Smoking contributed to more hepatocellular carcinomas in this Europe-wide cohort than chronic HBV and HCV infections. Heavy alcohol consumption and obesity also contributed to sizeable fractions of this disease burden. These contributions may be underestimates because EPIC volunteers are likely to be more health conscious than the general population.
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| 10. |
- Campa, Daniele, et al.
(författare)
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Genetic variability of the fatty acid synthase pathway is not associated with prostate cancer risk in the European Prospective Investigation on Cancer (EPIC)
- 2011
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 47:3, s. 420-427
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Tidskriftsartikel (refereegranskat)abstract
- A western lifestyle, characterised by low rates of energy expenditure and a high-energy diet rich in animal protein, saturated fats and refined carbohydrates, is associated with high incidence of prostate cancer in men. A high-energy nutritional status results in insulin/IGF signalling in cells, which in turn stimulates synthesis of fatty acids. We investigated whether the genetic variability of the genes belonging to the fatty acid synthesis pathway is related to prostate cancer risk in 815 prostate cancer cases and 1266 controls from the European Prospective Investigation on Cancer (EPIC). Using a tagging approach and selecting 252 SNPs in 22 genes, we covered all the common genetic variation of this pathway. None of the SNPs reached statistical significance after adjusting for multiple comparisons. Common SNPs in the fatty acid synthase pathway are not major contributors to prostate cancer risk.
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