| 61. |
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| 62. |
- Duell, Eric J., et al.
(författare)
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Genetic variation in alcohol dehydrogenase (ADH1A, ADH1B, ADH1C, ADH7) and aldehyde dehydrogenase (ALDH2), alcohol consumption and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort
- 2012
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Ingår i: Carcinogenesis. - Oxford : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 33:2, s. 361-367
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Tidskriftsartikel (refereegranskat)abstract
- Studies that have examined the association between alcohol consumption and gastric cancer (GC) risk have been inconsistent. We conducted an investigation of 29 genetic variants in alcohol metabolism loci (alcohol dehydrogenase, ADH1 gene cluster: ADH1A, ADH1B and ADH1C; ADH7 and aldehyde dehydrogenase, ALDH2), alcohol intake and GC risk. We analyzed data from a nested case-control study (364 cases and 1272 controls) within the European Prospective Investigation into Cancer and Nutrition cohort. Single nucleotide polymorphisms (SNPs) were genotyped using a customized array. We observed a statistically significant association between a common 3'-flanking SNP near ADH1A (rs1230025) and GC risk [allelic odds ratio (OR)(A v T) = 1.30, 95% confidence interval (CI) = 1.07-1.59]. Two intronic variants, one in ADH1C (rs283411) and one in ALDH2 (rs16941667), also were associated with GC risk (ORT v C = 0.59; 95% CI = 0.38-0.91 and ORT v C = 1.34; 95% CI = 1.00-1.79, respectively). Individuals carrying variant alleles at both ADH1 (rs1230025) and ALDH2 (rs16941667) were twice as likely to develop GC (ORA+T = 2.0; 95% CI = 1.25-3.20) as those not carrying variant alleles. The association between rs1230025 and GC was modified by alcohol intake (< 5 g/day: ORA = 0.89, 95% CI = 0.57-1.39; >= 5 g/day: ORA = 1.45, 95% CI = 1.08-1.94, P-value = 0.05). The association was also modified by ethanol intake from beer. A known functional SNP in ADH1B (rs1229984) was associated with alcohol intake (P-value = 0.04) but not GC risk. Variants in ADH7 were not associated with alcohol intake or GC risk. In conclusion, genetic variants at ADH1 and ALDH2 loci may influence GC risk, and alcohol intake may further modify the effect of ADH1 rs1230025. Additional population-based studies are needed to confirm our results.
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| 63. |
- Duell, Eric J, et al.
(författare)
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Menstrual and reproductive factors, exogenous hormone use, and gastric cancer risk in a cohort of women from the European Prospective Investigation Into Cancer and Nutrition
- 2010
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 172:12, s. 1384-1393
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Tidskriftsartikel (refereegranskat)abstract
- The worldwide incidence of gastric adenocarcinoma (GC) is lower in women than in men. Furthermore, cancer patients treated with estrogens have been reported to have a lower subsequent risk of GC. The authors conducted a prospective analysis of menstrual and reproductive factors, exogenous hormone use, and GC in 335,216 women from the European Prospective Investigation Into Cancer and Nutrition, a cohort study of individuals aged 35-70 years from 10 European countries. After a mean follow-up of 8.7 years (through 2004), 181 women for whom complete exposure data were available developed GC. Adjusted hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards models. All statistical tests were 2-sided. Women who had ovariectomy had a 79% increased risk of GC (based on 25 cases) compared with women who did not (hazard ratio = 1.79, 95% confidence interval: 1.15, 2.78). Total cumulative years of menstrual cycling was inversely associated with GC risk (fifth vs. first quintile: hazard ratio = 0.55, 95% confidence interval: 0.31, 0.98; P(trend) = 0.06). No other reproductive factors analyzed were associated with risk of GC. The results of this analysis provide some support for the hypothesis that endogenous ovarian sex hormones lower GC incidence in women.
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| 64. |
- Forouhi, Nita G., et al.
(författare)
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Differences in the prospective association between individual plasma phospholipid saturated fatty acids and incident type 2 diabetes : the EPIC-InterAct case-cohort study
- 2014
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Ingår i: LANCET DIABETES & ENDOCRINOLOGY. - 2213-8587 .- 2213-8595. ; 2:10, s. 810-818
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Tidskriftsartikel (refereegranskat)abstract
- Background Conflicting evidence exists regarding the association between saturated fatty acids (SFAs) and type 2 diabetes. In this longitudinal case-cohort study, we aimed to investigate the prospective associations between objectively measured individual plasma phospholipid SFAs and incident type 2 diabetes in EPIC-InterAct participants. Methods The EPIC-InterAct case-cohort study includes 12 403 people with incident type 2 diabetes and a representative subcohort of 16 154 individuals who were selected from a cohort of 340 234 European participants with 3 . 99 million person-years of follow-up (the EPIC study). Incident type 2 diabetes was ascertained until Dec 31, 2007, by a review of several sources of evidence. Gas chromatography was used to measure the distribution of fatty acids in plasma phospholipids (mol%); samples from people with type 2 diabetes and subcohort participants were processed in a random order by centre, and laboratory staff were masked to participant characteristics. We estimated country-specific hazard ratios (HRs) for associations per SD of each SFA with incident type 2 diabetes using Prentice-weighted Cox regression, which is weighted for case-cohort sampling, and pooled our findings using random-effects meta-analysis. Findings SFAs accounted for 46% of total plasma phospholipid fatty acids. In adjusted analyses, different individual SFAs were associated with incident type 2 diabetes in opposing directions. Even-chain SFAs that were measured (14: 0 [myristic acid], 16: 0 [palmitic acid], and 18: 0 [stearic acid]) were positively associated with incident type 2 diabetes (HR [95% CI] per SD difference: myristic acid 1.15 [95% CI 1.09-1.22], palmitic acid 1.26 [1.15-1.37], and stearic acid 1.06 [1.00-1.13]). By contrast, measured odd-chain SFAs (15: 0 [pentadecanoic acid] and 17: 0 [heptadecanoic acid]) were inversely associated with incident type 2 diabetes (HR [95% CI] per 1 SD difference: 0.79 [0.73-0.85] for pentadecanoic acid and 0.67 [0.63-0.71] for heptadecanoic acid), as were measured longer-chain SFAs (20: 0 [arachidic acid], 22:0 [behenic acid], 23:0 [tricosanoic acid], and 24:0 [lignoceric acid]), with HRs ranging from 0.72 to 0.81 (95% CIs ranging between 0.61 and 0.92). Our findings were robust to a range of sensitivity analyses. Interpretation Different individual plasma phospholipid SFAs were associated with incident type 2 diabetes in opposite directions, which suggests that SFAs are not homogeneous in their effects. Our findings emphasise the importance of the recognition of subtypes of these fatty acids. An improved understanding of differences in sources of individual SFAs from dietary intake versus endogenous metabolism is needed.
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| 65. |
- Fortner, Renee T., et al.
(författare)
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Correlates of circulating ovarian cancer early detection markers and their contribution to discrimination of early detection models : results from the EPIC cohort
- 2017
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Ingår i: Journal of Ovarian Research. - : Springer Science and Business Media LLC. - 1757-2215. ; 10
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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.
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| 66. |
- Fortner, Renee T., et al.
(författare)
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Endometrial cancer risk prediction including serum-based biomarkers : results from the EPIC cohort
- 2017
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 140:6, s. 1317-1323
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Tidskriftsartikel (refereegranskat)abstract
- Endometrial cancer risk prediction models including lifestyle, anthropometric and reproductive factors have limited discrimina-tion. Adding biomarker data to these models may improve predictive capacity; to our knowledge, this has not been investigat-ed for endometrial cancer. Using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we investigated the improvement in discrimination gained by adding serum biomarker concentrations to risk estimates derived from an existing risk prediction model based on epidemiologic factors. Serum concentrations of sex steroid hormones, metabolic markers, growth factors, adipokines and cytokines were evaluated in a step-wise backward selec-tion process; biomarkers were retained at p < 0.157 indicating improvement in the Akaike information criterion (AIC). Improvement in discrimination was assessed using the C-statistic for all biomarkers alone, and change in C-statistic from addition of biomarkers to preexisting absolute risk estimates. We used internal validation with bootstrapping (1000-fold) to adjust for over-fitting. Adiponectin, estrone, interleukin-1 receptor antagonist, tumor necrosis factor-alpha and triglycerides were select-ed into the model. After accounting for over-fitting, discrimination was improved by 2.0 percentage points when all evaluated biomarkers were included and 1.7 percentage points in the model including the selected biomarkers. Models including eti-ologic markers on independent pathways and genetic markers may further improve discrimination.
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| 67. |
- Fortner, Renée T., et al.
(författare)
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Ovarian cancer early detection by circulating CA125 in the context of anti-CA125 autoantibody levels : Results from the EPIC cohort
- 2018
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 142:7, s. 1355-1360
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Tidskriftsartikel (refereegranskat)abstract
- CA125 is the best ovarian cancer early detection marker to date; however, sensitivity is limited and complementary markers are required to improve discrimination between ovarian cancer cases and non-cases. Anti-CA125 autoantibodies are observed in circulation. Our objective was to evaluate whether these antibodies (1) can serve as early detection markers, providing evidence of an immune response to a developing tumor, and (2) modify the discriminatory capacity of CA125 by either masking CA125 levels (resulting in lower discrimination) or acting synergistically to improve discrimination between cases and non-cases. We investigated these objectives using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort (EPIC) including 250 cases diagnosed within 4 years of blood collection and up to four matched controls. Circulating CA125 antigen and antibody levels were quantified using an electrochemiluminescence assay. Adjusted areas under the curve (aAUCs) by 2-year lag-time intervals were calculated using conditional logistic regression calibrated toward the absolute risk estimates from a pre-existing epidemiological risk model as an offset-variable. Anti-CA125 levels alone did not discriminate cases from controls. For cases diagnosed <2 years after blood collection, discrimination by CA125 antigen was suggestively higher with higher anti-CA125 levels (aAUC, highest antibody tertile: 0.84 [0.76-0.92]; lowest tertile: 0.76 [0.67-0.86]; p(het)=0.06). We provide the first evidence of potentially synergistic discrimination effects of CA125 and anti-CA125 antibodies in ovarian early detection. If these findings are replicated, evaluating CA125 in the context of its antibody may improve ovarian cancer early detection. What's new? Although CA125, a mucin produced in epithelial cells, is a known marker for ovarian cancer, complementary biomarkers are necessary for reliable early cancer detection. Here, the authors examined autoantibodies against CA125 as potential pre-diagnosis markers. Although anti-CA125 levels did not discriminate between ovarian cases and controls, discrimination of CA125 differed by levels of its antibody, with the highest discrimination among women with the highest antibody levels. The authors propose that CA125 and anti-CA125 may act synergistically for ovarian cancer early detection.
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| 68. |
- Fortner, Renee T., et al.
(författare)
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Reproductive and hormone-related risk factors for epithelial ovarian cancer by histologic pathways, invasiveness and histologic subtypes: Results from the EPIC cohort
- 2015
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 137:5, s. 1196-1208
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Tidskriftsartikel (refereegranskat)abstract
- Whether risk factors for epithelial ovarian cancer (EOC) differ by subtype (i.e., dualistic pathway of carcinogenesis, histologic subtype) is not well understood; however, data to date suggest risk factor differences. We examined associations between reproductive and hormone-related risk factors for EOC by subtype in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Among 334,126 women with data on reproductive and hormone-related risk factors (follow-up: 1992-2010), 1,245 incident cases of EOC with known histology and invasiveness were identified. Data on tumor histology, grade, and invasiveness, were available from cancer registries and pathology record review. We observed significant heterogeneity by the dualistic model (i.e., type I [low grade serous or endometrioid, mucinous, clear cell, malignant Brenner] vs. type II [high grade serous or endometrioid]) for full-term pregnancy (p(het)=0.02). Full-term pregnancy was more strongly inversely associated with type I than type II tumors (ever vs. never: type I: relative risk (RR) 0.47 [95% confidence interval (CI): 0.33-0.69]; type II, RR: 0.81 [0.61-1.06]). We observed no significant differences in risk in analyses by major histologic subtypes of invasive EOC (serous, mucinous, endometrioid, clear cell). None of the investigated factors were associated with borderline tumors. Established protective factors, including duration of oral contraceptive use and full term pregnancy, were consistently inversely associated with risk across histologic subtypes (e.g., ever full-term pregnancy: serous, RR: 0.73 [0.58-0.92]; mucinous, RR: 0.53 [0.30-0.95]; endometrioid, RR: 0.65 [0.40-1.06]; clear cell, RR: 0.34 [0.18-0.64]; p(het)=0.16). These results suggest limited heterogeneity between reproductive and hormone-related risk factors and EOC subtypes. What's new? Reproductive and hormone-related risk factors for epithelial ovarian cancer (EOC) have been extensively investigated. However, EOC is increasingly recognized as a heterogeneous disease and risk factor differences across EOC subtypes, as defined by the recently proposed dualistic pathway of ovarian carcinogenesis and histological characteristics, are not well understood. Here, the authors present a detailed prospective investigation on reproductive and hormone-related risk factors for borderline tumors and epithelial ovarian cancer by main histological subtypes and, for the first time, by the types defined by the dualistic pathway. The results suggest limited heterogeneity between reproductive and hormone-related risk factors and EOC subtypes.
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| 69. |
- Freisling, Heinz, et al.
(författare)
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Nut intake and 5-year changes in body weight and obesity risk in adults: results from the EPIC-PANACEA study
- 2018
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Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6207 .- 1436-6215. ; 57:7, s. 2399-2408
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 Springer-Verlag GmbH Germany Purpose: There is inconsistent evidence regarding the relationship between higher intake of nuts, being an energy-dense food, and weight gain. We investigated the relationship between nut intake and changes in weight over 5 years. Methods: This study includes 373,293 men and women, 25–70 years old, recruited between 1992 and 2000 from 10 European countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Habitual intake of nuts including peanuts, together defined as nut intake, was estimated from country-specific validated dietary questionnaires. Body weight was measured at recruitment and self-reported 5 years later. The association between nut intake and body weight change was estimated using multilevel mixed linear regression models with center/country as random effect and nut intake and relevant confounders as fixed effects. The relative risk (RR) of becoming overweight or obese after 5 years was investigated using multivariate Poisson regressions stratified according to baseline body mass index (BMI). Results: On average, study participants gained 2.1 kg (SD 5.0 kg) over 5 years. Compared to non-consumers, subjects in the highest quartile of nut intake had less weight gain over 5 years (−0.07 kg; 95% CI −0.12 to −0.02) (P trend = 0.025) and had 5% lower risk of becoming overweight (RR 0.95; 95% CI 0.92–0.98) or obese (RR 0.95; 95% CI 0.90–0.99) (both P trend < 0.008). Conclusions: Higher intake of nuts is associated with reduced weight gain and a lower risk of becoming overweight or obese.
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| 70. |
- Gallo, Valentina, et al.
(författare)
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Parkinson's Disease Case Ascertainment in the EPIC Cohort : The NeuroEPIC4PD Study
- 2015
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Ingår i: Neurodegenerative Diseases. - : S. Karger. - 1660-2854 .- 1660-2862. ; 15:6, s. 331-338
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Large epidemiological prospective studies represent an important opportunity for investigating risk factors for rare diseases such as Parkinson's disease (PD). Here we describe the procedures we used for ascertaining PD cases in the EPIC (European Prospective Investigation into Cancer and Nutrition) study. Methods: The following three-phase procedure was used: (1) elaboration of a NeuroEPIC4PD template for clinical data collection, (2) identification of all potential PD cases via record linkage and (3) validation of the diagnosis through clinical record revision, in a population of 220,494 subjects recruited in 7 European countries. All cases were labelled with the NeuroEPIC4PD diagnoses of 'definite', 'very likely', 'probable', or 'possible' PD. Results: A total of 881 PD cases were identified, with over 2,741,780 person-years of follow-up (199 definite, 275 very likely, 146 probable, and 261 possible). Of these, 734 were incident cases. The mean age at diagnosis was 67.9 years (SD 9.2) and 458 patients (52.0%) were men. Bradykinesia was the most frequent presenting motor sign (76.5%). Tremor-dominant and akinetic rigid forms of PD were the most common types of PD. A total of 289 patients (32.8%) were dead at the time of the last follow-up. Conclusions: This exercise proved that it is feasible to ascertain PD in large population-based cohort studies and offers a potential framework to be replicated in similar studies.
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