| 51. |
- Huyghe, Jeroen R, et al.
(författare)
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Genetic architectures of proximal and distal colorectal cancer are partly distinct
- 2021
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Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 70:7, s. 1325-1334
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Tidskriftsartikel (refereegranskat)abstract
- Objective: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined.Design: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling.Results: We identified 13 loci that reached genome-wide significance (p<5×10-8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer.Conclusion: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.
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| 52. |
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| 53. |
- Jay, R, et al.
(författare)
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Alcohol consumption and the risk of renal cancers in the European Prospective Investigation into Cancer and Nutrition (EPIC). Wozniak MB, Brennan P, Brenner DR, Overvad K, Olsen A, Tjønneland A, Boutron-Ruault MC, Clavel-Chapelon F, Fagherazzi G, Katzke V, Kühn T, Boeing H, Bergmann MM, Steffen A, Naska A, Trichopoulou A, Trichopoulos D, Saieva C, Grioni S, Panico S, Tumino R, Vineis P, Bueno-de-Mesquita HB, Peeters PH, Hjartåker A, Weiderpass E, Arriola L, Molina-Montes E, Duell EJ, Santiuste C, Alonso de la Torre R, Barricarte Gurrea A, Stocks T, Johansson M, Ljungberg B, Wareham N, Khaw KT, Travis RC, Cross AJ, Murphy N, Riboli E, Scelo G.Int J Cancer. 2015 Oct 15;137(8):1953-66. [Epub 2015 Apr 28]. doi: 10.1002/ijc.29559
- 2017
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Ingår i: Urologic oncology. - : Elsevier BV. - 1873-2496. ; 35:3, s. 117-
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Tidskriftsartikel (refereegranskat)
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| 54. |
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| 55. |
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| 56. |
- Schmit, Stephanie L, et al.
(författare)
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Novel Common Genetic Susceptibility Loci for Colorectal Cancer.
- 2019
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 111:2, s. 146-157
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk.Methods: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided.Results: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0.Conclusions: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.
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| 57. |
- Tsilidis, K. K., et al.
(författare)
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Oral contraceptives, reproductive history and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition
- 2010
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 103:11, s. 1755-1759
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Oral contraceptive use and reproductive factors may initiate long-term changes to the hormonal milieu and thereby, possibly influence colorectal cancer risk. METHODS: We examined the association of hormonal and reproductive factors with risk of colorectal cancer among 337 802 women in the European Prospective Investigation into Cancer and Nutrition, of whom 1878 developed colorectal cancer. RESULTS: After stratification for center and age, and adjustment for body mass index, smoking, diabetes mellitus, physical activity and alcohol consumption, ever use of oral contraceptives was marginally inversely associated with colorectal cancer risk (hazard ratio (HR), 0.92; 95% confidence interval (CI), 0.83-1.02), although this association was stronger among post-menopausal women (HR, 0.84; 95% CI: 0.74-0.95). Duration of oral contraceptive use and reproductive factors, including age at menarche, age at menopause, type of menopause, ever having an abortion, parity, age at first full-term pregnancy and breastfeeding, were not associated with colorectal cancer risk. CONCLUSION: Our findings provide limited support for a potential inverse association between oral contraceptives and colorectal cancer risk. British Journal of Cancer (2010) 103, 1755-1759. doi:10.1038/sj.bjc.6605965 www.bjcancer.com Published online 2 November 2010 (C) 2010 Cancer Research UK
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| 58. |
- van Bakel, M. M. E., et al.
(författare)
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Dietary glycaemic index and glycaemic load in the European Prospective Investigation into Cancer and Nutrition
- 2009
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 1476-5640 .- 0954-3007. ; 63:4s, s. 188-205
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To describe dietary glycaemic index (GI) and glycaemic load (GL) values in the population participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study according to food groups, nutrients and lifestyle characteristics. Methods: Single 24-h dietary recalls (24-HDRs) from 33 566 subjects were used to calculate dietary GI and GL, and an ad hoc database was created as the main reference source. Mean GI and GL intakes were adjusted for age, total energy intake, height and weight, and were weighted by season and day of recall. Results: GI was the lowest in Spain and Germany, and highest in the Netherlands, United Kingdom and Denmark for both genders. In men, GL was the lowest in Spain and Germany and highest in Italy, whereas in women, it was the lowest in Spain and Greece and highest in the UK health-conscious cohort. Bread was the largest contributor to GL in all centres (15-45%), but it also showed the largest inter-individual variation. GL, but not GI, tended to be lower in the highest body mass index category in both genders. GI was positively correlated with starch and intakes of bread and potatoes, whereas it was correlated negatively with intakes of sugar, fruit and dairy products. GL was positively correlated with all carbohydrate components and intakes of cereals, whereas it was negatively correlated with fat and alcohol and with intakes of wine, with large variations across countries. Conclusions: GI means varied modestly across countries and genders, whereas GL means varied more, but it may possibly act as a surrogate of carbohydrate intake. European Journal of Clinical Nutrition (2009) 63, S188-S205; doi: 10.1038/ejcn.2009.81
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| 59. |
- van Gils, C H, et al.
(författare)
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Consumption of vegetables and fruits and risk of breast cancer
- 2005
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Ingår i: JAMA: The Journal of the American Medical Association. - 1538-3598. ; 293:2, s. 183-193
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Tidskriftsartikel (refereegranskat)abstract
- Context The intake of vegetables and fruits has been thought to protect against breast cancer. Most of the evidence comes from case-control studies, but a recent pooled analysis of the relatively few published cohort studies suggests no significantly reduced breast cancer risk is associated with vegetable and fruit consumption. Objective To examine the relation between total and specific vegetable and fruit intake and the incidence of breast cancer. Design, Setting, and Participants Prospective study of 285526 women between the ages of 25 and 70 years, participating in the European Prospective Investigation Into Cancer and Nutrition (EPIC) study, recruited from 8 of the 10 participating European countries. Participants completed a dietary questionnaire in 1992-1998 and were followed up for incidence of cancer until 2002. Main Outcome Measures Relative risks for breast cancer by total and specific vegetable and fruit intake. Analyses were stratified by age at recruitment and study center. Relative risks were adjusted for established breast cancer risk factors. Results During 1486402 person-years (median duration of follow-up, 5.4 years), 3659 invasive incident breast cancer cases were reported. No significant associations between vegetable or fruit intake and breast cancer risk were observed. Relative risks for the highest vs the lowest quintile were 0.98 (95% confidence interval [CI], 0.84-1.14) for total vegetables, 1.09 (95% Cl, 0.94-1.25) for total fruit, and 1.05 (95% Cl, 0.92-1.20) for fruit and vegetable juices. For 6 specific vegetable subgroups no associations with breast cancer risk were observed either. Conclusion Although the period of follow-up is limited for now, the results suggest that total or specific vegetable and fruit intake is not associated with risk for breast cancer.
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| 60. |
- Bamia, C., et al.
(författare)
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Fruit and vegetable consumption in relation to hepatocellular carcinoma in a multi-centre, European cohort study
- 2015
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 112:7, s. 1273-1282
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Tidskriftsartikel (refereegranskat)abstract
- Background:Vegetable and/or fruit intakes in association with hepatocellular carcinoma (HCC) risk have been investigated in case-control studies conducted in specific European countries and cohort studies conducted in Asia, with inconclusive results. No multi-centre European cohort has investigated the indicated associations. Methods: In 486 799 men/women from the European Prospective Investigation into Cancer and nutrition, we identified 201 HCC cases after 11 years median follow-up. We calculated adjusted hazard ratios (HRs) for HCC incidence for sex-specific quintiles and per 100 g d(-1) increments of vegetable/fruit intakes. Results: Higher vegetable intake was associated with a statistically significant, monotonic reduction of HCC risk: HR (100 g d(-1) increment): 0.83; 95% CI: 0.71-0.98. This association was consistent in sensitivity analyses with no apparent heterogeneity across strata of HCC risk factors. Fruit intake was not associated with HCC incidence: HR (100 g d(-1) increment): 1.01; 95% CI: 0.92-1.11. Conclusions: Vegetable, but not fruit, intake is associated with lower HCC risk with no evidence for heterogeneity of this association in strata of important HCC risk factors. Mechanistic studies should clarify pathways underlying this association. Given that HCC prognosis is poor and that vegetables are practically universally accessible, our results may be important, especially for those at high risk for the disease.
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