| 281. |
- Murphy, Neil, et al.
(författare)
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Heterogeneity of Colorectal Cancer Risk Factors by Anatomical Subsite in 10 European Countries : A Multinational Cohort Study
- 2019
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 17:7, s. 1323-1331
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Colorectal cancer located at different anatomical subsites may have distinct etiologies and risk factors. Previous studies that have examined this hypothesis have yielded inconsistent results, possibly because most studies have been of insufficient size to identify heterogeneous associations with precision.Methods: In the European Prospective Investigation into Cancer and Nutrition study, we used multivariable joint Cox proportional hazards models, which accounted for tumorsat different anatomical sites (proximal colon, distal colon, and rectum) as competing risks, to examine the relationships between 14 established/suspected lifestyle, anthropometric, and reproductive/menstrual risk factors with colorectal cancer risk. Heterogeneity across sites was tested using Wald tests.Results: After a median of 14.9 years of follow-up of 521,330 men and women, 6291 colorectal cancer cases occurred. Physical activity was related inversely to proximal colon and distal colon cancer, but not to rectal cancer (P heterogeneity = .03). Height was associated positively with proximal and distal colon cancer only, but not rectal cancer (P heterogeneity = .0001). For men, but not women, heterogeneous relationships were observed for body mass index (P heterogeneity = .008) and waist circumference (P heterogeneity = .03), with weaker positive associations found for rectal cancer, compared with proximal and distal colon cancer. Current smoking was associated with a greater risk of rectal and proximal colon cancer, but not distal colon cancer (P heterogeneity = .05). No heterogeneity by anatomical site was found for alcohol consumption, diabetes, nonsteroidal anti-inflammatory drug use, and reproductive/menstrual factors.Conclusions: The relationships between physical activity, anthropometry, and smoking with colorectal cancer risk differed by subsite, supporting the hypothesis that tumors in different anatomical regions may have distinct etiologies.
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| 282. |
- Nead, Kevin T., et al.
(författare)
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Contribution of common non-synonymous variants in PCSK1 to body mass index variation and risk of obesity : a systematic review and meta-analysis with evidence from up to 331 175 individuals
- 2015
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:12, s. 3582-3594
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Tidskriftsartikel (refereegranskat)abstract
- Polymorphisms rs6232 and rs6234/rs6235 in PCSK1 have been associated with extreme obesity [e.g. body mass index (BMI) a parts per thousand yen 40 kg/m(2)], but their contribution to common obesity (BMI a parts per thousand yen 30 kg/m(2)) and BMI variation in a multi-ethnic context is unclear. To fill this gap, we collected phenotypic and genetic data in up to 331 175 individuals from diverse ethnic groups. This process involved a systematic review of the literature in PubMed, Web of Science, Embase and the NIH GWAS catalog complemented by data extraction from pre-existing GWAS or custom-arrays in consortia and single studies. We employed recently developed global meta-analytic random-effects methods to calculate summary odds ratios (OR) and 95% confidence intervals (CIs) or beta estimates and standard errors (SE) for the obesity status and BMI analyses, respectively. Significant associations were found with binary obesity status for rs6232 (OR = 1.15, 95% CI 1.06-1.24, P = 6.08 x 10(-6)) and rs6234/rs6235 (OR = 1.07, 95% CI 1.04-1.10, P = 3.00 x 10(-7)). Similarly, significant associations were found with continuous BMI for rs6232 (beta = 0.03, 95% CI 0.00-0.07; P = 0.047) and rs6234/rs6235 (beta = 0.02, 95% CI 0.00-0.03; P = 5.57 x 10(-4)). Ethnicity, age and study ascertainment significantly modulated the association of PCSK1 polymorphisms with obesity. In summary, we demonstrate evidence that common gene variation in PCSK1 contributes to BMI variation and susceptibility to common obesity in the largest known meta-analysis published to date in genetic epidemiology.
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| 283. |
- Neasham, David, et al.
(författare)
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Double-strand break DNA repair genotype predictive of later mortality and cancer incidence in a cohort of non-smokers
- 2009
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Ingår i: DNA Repair. - : Elsevier BV. - 1568-7856 .- 1568-7864. ; 8:1, s. 60-71
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Tidskriftsartikel (refereegranskat)abstract
- We followed-up for mortality and cancer incidence 1088 healthy non-smokers from a population-based study, who were characterized for 22 variants in 16 genes involved in DNA repair pathways. Follow-up was 100% complete. The association between polymorphism and mortality or cancer incidence was analyzed using Cox Proportional Hazard regression models. Ninety-five subjects had died in a median follow-up time of 78 months (inter-quartile range 59-93 months). None of the genotypes was clearly associated with total mortality, except variants for two Double-Strand Break DNA repair genes, XRCC3 18067 C > T (rs#861539) and XRCC2 31479 G > A (rs#3218536). Adjusted hazard ratios were 2.25 (1.32-3.83) for the XRCC3 C/T genotype and 2.04 (1.00-4.13) for the T/T genotype (reference C/C), and 2.12 (1.14-3.97) for the XRCC2 G/A genotype (reference G/G). For total cancer mortality, the adjusted hazard ratios were 3.29 (1.23-7.82) for XRCC3 C/T, 2.84 (0.81-9.90) for XRCC3 T/T and 3.17 (1.21-8.30) for XRCC2 G/A. With combinations of three or more adverse alleles, the adjusted hazard ratio for all cause mortality was 17.29 (95% C.I. 8.13-36.74), and for all incident cancers the HR was 5.28 (95% C.I. 2.17-12.85). Observations from this prospective study suggest that polymorphisms of genes involved in the repair of DNA double-strand breaks significantly influence the risk of cancer and non-cancer disease, and call influence mortality. (C) 2008 Elsevier B.V. All rights reserved.
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| 284. |
- Neasham, David, et al.
(författare)
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Occupation and risk of lymphoma : a multicentre prospective cohort study (EPIC)
- 2011
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Ingår i: Occupational and Environmental Medicine. - : BMJ. - 1351-0711 .- 1470-7926. ; 68:1, s. 77-81
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Tidskriftsartikel (refereegranskat)abstract
- The findings in this current study of a higher risk of NHL among car repair workers and butchers and a higher risk of HL among gasoline station workers suggest a possible role from occupationally related exposures, such as solvents and zoonotic viruses, as risk factors for malignant lymphoma.
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| 285. |
- Newton-Cheh, Christopher, et al.
(författare)
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Genome-wide association study identifies eight loci associated with blood pressure
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:6, s. 666-676
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N <= 71,225 European ancestry, N <= 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 x 10(-24)), CYP1A2 (P = 1 x 10(-23)), FGF5 (P = 1 x 10(-21)), SH2B3 (P = 3 x 10(-18)), MTHFR (P = 2 x 10(-13)), c10orf107 (P = 1 x 10(-9)), ZNF652 (P = 5 x 10(-9)) and PLCD3 (P = 1 x 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.
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| 286. |
- Nieters, Alexandra, et al.
(författare)
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Smoking and lymphoma risk in the european prospective investigation into cancer and nutrition
- 2008
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 167:9, s. 1081-1089
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Tidskriftsartikel (refereegranskat)abstract
- Lymphomas are one of the few cancers that have been increasing in incidence over the past decades. So far, only a few established risk factors have been identified, including immunosuppression and viral infections. Recent evidence suggests etiologic heterogeneity of different lymphoma subtypes. Smoking may affect risk differently, depending on the lymphoma entity. The European Prospective Investigation into Cancer and Nutrition was used to study the role of smoking in the etiology of lymphomas and individual subtypes within a prospective study. Information on baseline and lifetime tobacco smoking by 478,590 participants was collected between 1992 and 2000. Cox proportional hazards regression was used to calculate multivariate-adjusted hazard ratios and 95% confidence intervals. During 3,567,410 person-years of follow-up, 1,371 lymphoma cases (1,304 non-Hodgkin's lymphomas and 67 Hodgkin's lymphomas) were identified. Relative risk for smokers at recruitment was more than twofold higher for Hodgkin's lymphoma (hazard ratio = 2.14, 95% confidence interval: 1.18, 3.87) but was not elevated for non-Hodgkin's lymphoma (hazard ratio = 1.06, 95% confidence interval: 0.94, 1.19) and individual B-cell non-Hodgkin's lymphoma subtypes. In this prospective study, smoking appeared to increase Hodgkin's lymphoma risk consistently in both genders, whereas B-cell non-Hodgkin's lymphoma risk was not associated. Future analysis should involve viral biomarkers and genetic susceptibility markers to elucidate potential mechanisms of smoking-induced carcinogenesis, particularly for Hodgkin's lymphoma.
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| 287. |
- Nimptsch, Katharina, et al.
(författare)
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Association of CRP genetic variants with blood concentrations of C-reactive protein and colorectal cancer risk.
- 2015
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 136:5, s. 1181-1192
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Tidskriftsartikel (refereegranskat)abstract
- High blood concentrations of C-reactive protein (CRP) have been associated with elevated risk of colorectal cancer in several prospective studies including the European Prospective Investigation into Cancer and Nutrition (EPIC), but it is unknown whether these observations reflect a causal relationship. We aimed to investigate whether CRP genetic variants associated with lifelong higher CRP concentrations translate into higher colorectal cancer risk. We conducted a prospective nested case-control study within EPIC including 727 cases diagnosed between 1992 and 2003 and 727 matched controls selected according to an incidence-density sampling protocol. Baseline CRP concentrations were measured in plasma samples by a high sensitivity assay. Tagging single nucleotide polymorphisms (SNPs) in the CRP gene (rs1205, rs1800947, rs1130864, rs2808630, rs3093077) were identified via HapMap. The causal effect of CRP on colorectal cancer risk was examined in a Mendelian Randomization approach utilizing multiple CRP genetic variants as instrumental variables. The SNPs rs1205, rs1800947, rs1130864 and rs3093077 were significantly associated with CRP concentrations and were incorporated in a CRP allele score which was associated with 13% higher CRP concentrations per allele count (95% confidence interval 8-19%). Using the CRP-score as instrumental variable, genetically twofold higher CRP concentrations were associated with higher risk of colorectal cancer (odds ratio 1.74, 95% confidence interval 1.06-2.85). Similar observations were made using alternative definitions of instrumental variables. Our findings give support to the hypothesis that elevated circulating CRP may play a direct role in the etiology of colorectal cancer.
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| 288. |
- Nimptsch, Katharina, et al.
(författare)
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Plasma fetuin-A concentration, genetic variation in the AHSG gene and risk of colorectal cancer
- 2015
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 137:4, s. 911-920
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Tidskriftsartikel (refereegranskat)abstract
- Fetuin-A, also referred to as alpha 2-Heremans-Schmid glycoprotein (AHSG), is a liver protein known to inhibit insulin actions. Hyperinsulinemia is a possible risk factor for colorectal cancer; however, the role of fetuin-A in the development of colorectal cancer is unclear. We investigated the association between circulating fetuin-A and colorectal cancer risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. Fetuin-A concentrations were measured in prediagnostic plasma samples from 1,367 colorectal cancer cases and 1,367 matched controls. In conditional logistic regression models adjusted for potential confounders, the estimated relative risk (95% confidence interval) of colorectal cancer per 40 mg/mL higher fetuin-A concentrations (approximately one standard deviation) was 1.13 (1.02-1.24) overall, 1.21 (1.05-1.39) in men, 1.06 (0.93-1.22) in women, 1.13 (1.00-1.27) for colon cancer and 1.12 (0.94-1.32) for rectal cancer. To improve causal inference in a Mendelian Randomization approach, five tagging single nucleotide polymorphisms of the AHSG gene were genotyped in a subset of 456 case-control pairs. The AHSG allele-score explained 21% of the interindividual variation in plasma fetuin-A concentrations. In instrumental variable analysis, genetically raised fetuin-A was not associated with colorectal cancer risk (relative risk per 40 mg/mL genetically determined higher fetuin-A was 0.98, 95% confidence interval: 0.73-1.33). The findings of our study indicate a modest linear association between fetuin-A concentrations and risk of colorectal cancer but suggest that fetuin-A may not be causally related to colorectal cancer development.
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| 289. |
- Noethlings, Ute, et al.
(författare)
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Intake of vegetables, legumes, and fruit, and risk for all-cause, cardiovascular, and cancer mortality in a European diabetic population
- 2008
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Ingår i: Journal of Nutrition. - 1541-6100. ; 138:4, s. 775-781
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Tidskriftsartikel (refereegranskat)abstract
- We examined the associations of intake of vegetables, legumes and fruit with all-cause and cause-specific mortality in a population with prevalent diabetes in Europe. A cohort of 10,449 participants with self-reported diabetes within the European Prospective Investigation into Cancer and Nutrition study was followed for a mean of 9 y. Intakes of vegetables, legumes, and fruit were assessed at baseline between 1992 and 2000 using validated country-specific questionnaires. A total of 1346 deaths occurred. Multivariate relative risks (RR) for all-cause mortality were estimated in Cox regression models and FIR for cause-specific mortality were derived in a competing risk model. An increment in intake of total vegetables, legumes, and fruit of 80 g/d was associated with a RR of death from all causes of 0.94 [95% CI 0.90-0.98]. Analyzed separately, vegetables and legumes were associated with a significantly reduced risk, whereas nonsignificant inverse associations for fruit intake were observed. Cardiovascular disease (CVD) mortality and mortality due to non-CVD/non-cancer causes were significantly inversely associated with intake of total vegetables, legumes, and fruit (RR 0.88 [95% CI 0.81-0.95] and 0.90 [0.82-0.99], respectively) but not cancer mortality 0.08 [0.99-1.17]). Intake of vegetables, legumes, and fruit was associated with reduced risks of all-cause and CVD mortality in a diabetic population. The findings support the current state of evidence from general population studies that the protective potential of vegetable and fruit intake is larger for CVD than for cancer and suggest that diabetes patients may benefit from a diet high in vegetables and fruits.
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| 290. |
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