| 61. |
- Strömberg, Ulf, et al.
(author)
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Selection of Influential Genetic Markers Among a Large Number of Candidates Based on Effect Estimation Rather than Hypothesis Testing: An Approach for Genome-Wide Association Studies.
- 2008
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In: Epidemiology. - 1531-5487. ; 19, s. 302-308
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Journal article (peer-reviewed)abstract
- In epidemiologic studies on direct genetic associations, hypothesis testing is primarily considered for evaluating the effects of each candidate genetic marker, eg, single nucleotide polymorphisms. To help investigators protect themselves from over-interpreting statistically significant findings that are not likely to signify a true effect-a problem connected to multiple comparisons-consideration of the false-positive report probability has been proposed. There have also been arguments advocating estimation of effect size rather than hypothesis testing (P value). Here, we propose an estimation-based approach that offers an attractive alternative to the test-based false-positive report probability, when the task is to select promising genetic markers for further analyses. We discuss the potential of this estimation-based approach for genome-wide association studies.
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| 62. |
- Tjonneland, Anne, et al.
(author)
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Alcohol intake and breast cancer risk: the European Prospective Investigation into Cancer and Nutrition (EPIC)
- 2007
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In: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 1573-7225 .- 0957-5243. ; 18:4, s. 361-373
-
Journal article (peer-reviewed)abstract
- Objective Most epidemiologic studies have suggested an increased risk of breast cancer with increasing alcohol intake. Using data from 274,688 women participating in the European Prospective Investigation into Cancer and Nutrition study (EPIC), we investigated the relation between alcohol intake and the risk of breast cancer. Methods Incidence rate ratios (IRRs) based on Cox proportional hazard models were calculated using reported intake of alcohol, recent (at baseline) and lifetime exposure. We adjusted for known risk factors and stratified according to study center as well as potentially modifying host factors. Results During 6.4 years of follow up, 4,285 invasive cases of breast cancer within the age group 35-75 years were identified. For all countries together the IRR per 10 g/day higher recent alcohol intake (continuous) was 1.03 (95% confidence interval (CI): 1.01-1.05). When adjusted, no association was seen between lifetime alcohol intake and risk of breast cancer. No difference in risk was shown between users and non-users of HRT, and there was no significant interaction between alcohol intake and BMI, HRT or dietary folate. Conclusion This large European study supports previous findings that recent alcohol intake increases the risk of breast cancer.
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| 63. |
- Travier, Noemie, et al.
(author)
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Smoking and body fatness measurements: A cross-sectional analysis in the EPIC-PANACEA study
- 2009
-
In: Preventive Medicine. - New York : Elsevier BV. - 1096-0260 .- 0091-7435. ; 49:5, s. 365-373
-
Journal article (peer-reviewed)abstract
- Objective. The present study investigates the cross-sectional relationship between tobacco smoking and body fatness. Methods. This cross-sectional study consisted of 469,543 men and women who participated in the European Prospective Investigation into Cancer and Nutrition (EPIC) study between 1992 and 2000 providing anthropometric measurements and information on smoking. Adjusted multilevel mixed-effects linear regression models were used to assess the association between smoking and body fat mass. Results. The analyses showed that BMI and WC were positively associated with smoking intensity in current smokers but negatively associated with time since quitting in former smokers. When compared to never smokers, average current smokers (17 and 13 cig/day for men and women, respectively) showed a lower BMI. When average former smokers (men and women who had stopped smoking for 16 and 15 years, respectively) were compared to never smokers, higher BMI and WC were observed in men, whereas no significant associations were observed in women. Conclusions. This cross-sectional study suggests that smoking may be associated with body fatness and fat distribution. Although our findings cannot establish cause and effect, they suggest that providing information and support to those who want to stop may help in preventing weight gain and therefore weaken a barrier against stopping smoking. (C) 2009 Elsevier Inc. All rights reserved.
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| 64. |
- Travis, Ruth C., et al.
(author)
-
CYP19A1 Genetic Variation in Relation to Prostate Cancer Risk and Circulating Sex Hormone Concentrations in Men from the Breast and Prostate Cancer Cohort Consortium
- 2009
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In: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 18:10, s. 2734-2744
-
Journal article (peer-reviewed)abstract
- Sex hormones, particularly the androgens, are important for the growth of the prostate gland and have been implicated in prostate cancer carcinogenesis, yet the determinants of endogenous steroid hormone levels remain poorly understood. Twin studies suggest a heritable component for circulating concentrations of sex hormones, although epidemiologic evidence linking steroid hormone gene variants to prostate cancer is limited. Here we report on findings from a comprehensive study of genetic variation at the CYP19A1 locus in relation to prostate cancer risk and to circulating steroid hormone concentrations in men by the Breast and Prostate Cancer Cohort Consortium (BPC3), a large collaborative prospective study. The BPC3 systematically characterized variation in CYP19A1 by targeted resequencing and dense genotyping; selected haplotype-tagging single nuclecitide polymorphisms (htSNP) that efficiently predict common variants in U.S. and Europe-an whites, Latinos, Japanese Americans, and Native Hawaiians; and genotyped these htSNPs; in 8,166 prostate cancer cases and 9,079 study-, age-, and ethnicity-matched controls. CYP19A1 htSNPs, two common missense variants and common haplotypes were not significantly associated with risk of prostate cancer. However, several htSNPs in linkage disequilibrium blocks 3 and 4 were significantly associated with a 5% to 10% difference in estradiol concentrations in men [association per copy of the two-SNP haplotype rs749292-rs727479 (A-A) versus noncarriers; P = 1 x 10(-5)], and with inverse, although less marked changes, in free testosterone concentrations. These results suggest that although germline variation in CYP19A1 characterized by the htSNPs produces measurable differences in sex hormone concentrations in men, they do not substantially influence risk of prostate cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(10):2734-44)
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| 65. |
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| 66. |
- Travis, Ruth C, et al.
(author)
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Serum vitamin D and risk of prostate cancer in a case-control analysis nested within the European Prospective Investigation into Cancer and Nutrition (EPIC).
- 2009
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In: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 169:10, s. 1223-1232
-
Journal article (peer-reviewed)abstract
- Results from the majority of studies show little association between circulating concentrations of vitamin D and prostate cancer risk, a finding that has not been demonstrated in a wider European population, however. The authors examined whether vitamin D concentrations were associated with prostate cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (1994-2000). Serum concentrations of 25-hydroxyvitamin D were measured in 652 prostate cancer cases matched to 752 controls from 7 European countries after a median follow-up time of 4.1 years. Conditional logistic regression models were used to calculate odds ratios for prostate cancer risk in relation to serum 25-hydroxyvitamin D after standardizing for month of blood collection and adjusting for covariates. No significant association was found between 25-hydroxyvitamin D and risk of prostate cancer (highest vs. lowest quintile: odds ratio = 1.28, 95% confidence interval: 0.88, 1.88; P for trend = 0.188). Subgroup analyses showed no significant heterogeneity by cancer stage or grade, age at diagnosis, body mass index, time from blood collection to diagnosis, or calcium intake. In summary, the results of this large nested case-control study provide no evidence in support of a protective effect of circulating concentrations of vitamin D on the risk of prostate cancer.
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| 67. |
- Vaissière, Thomas, et al.
(author)
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Quantitative analysis of DNA methylation after whole bisulfitome amplification of a minute amount of DNA from body fluids.
- 2009
-
In: Epigenetics : official journal of the DNA Methylation Society. - 1559-2308. ; 4:4, s. 221-30
-
Journal article (peer-reviewed)abstract
- Cell-free circulating DNA isolated from the plasma of individuals with cancer has been shown to harbor cancer-associated changes in DNA methylation, and thus it represents an attractive target for biomarker discovery. However, the reliable detection of DNA methylation changes in body fluids has proven to be technically challenging. Here we describe a novel combination of methods that allows quantitative and sensitive detection of DNA methylation in minute amounts of DNA present in body fluids (quantitative Methylation Analysis of Minute DNA amounts after whole Bisulfitome Amplification, qMAMBA). This method involves genome-wide amplification of bisulphite-modified DNA template followed by quantitative methylation detection using pyrosequencing and allows analysis of multiple genes from a small amount of starting DNA. To validate our method we used qMAMBA assays for four genes and LINE1 repetitive sequences combined with plasma DNA samples as a model system. qMAMBA offered high efficacy in the analysis of methylation levels and patterns in plasma samples with extremely small amounts of DNA and low concentrations of methylated alleles. Therefore, qMAMBA will facilitate methylation studies aiming to discover epigenetic biomarkers, and should prove particularly valuable in profiling a large sample series of body fluids from molecular epidemiology studies as well as in tracking disease in early diagnostics.
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| 68. |
- Vesper, Hubert W., et al.
(author)
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Cross-sectional study on acrylamide hemoglobin adducts in subpopulations from the European Prospective Investigation into Cancer and Nutrition (EPIC) study
- 2008
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In: Journal of Agricultural and Food Chemistry. - : American Chemical Society (ACS). - 0021-8561 .- 1520-5118. ; 56:15, s. 6046-6053
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Journal article (peer-reviewed)abstract
- Acrylamide exposure was investigated in subgroups of the EPIC study population (510 subjects from 9 European countries, randomly selected and stratified by age, gender, and smoking status) using hemoglobin adducts of acrylamide (HbAA) and its primary metabolite glycidamide (HbGA). Blood samples were analyzed for HbAA and HbGA by HPLC/MS/MS. Statistical models for HbAA and HbGA were developed including body mass index (BMI), educational level, and physical activity. A large variability in acrylamide exposure and metabolism between individuals and country groups was observed with HbAA and HbGA values ranging between 15-623 and 8-377 pmol/g of Hb, respectively. Both adducts differed significantly by country, sex, and smoking status. HbGA values were significantly lower in high alcohol consumers than in moderate consumers. With increasing BMI, HbGA in nonsmokers and HbAA in smokers decreased significantly. In the assessment of potential health effects related to acrylamide exposure, country of origin, BMI, alcohol consumption, sex, and smoking status should be considered.
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| 69. |
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| 70. |
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