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Interaction between dietary acrylamide intake and genetic variants for estrogen receptor-positive breast cancer risk.

ABSTRACT: PURPOSE:The association between dietary acrylamide intake and estrogen receptor-positive (ER+) breast cancer risk in epidemiological studies is inconsistent. By analyzing gene-acrylamide interactions for ER+?breast cancer risk, we aimed to clarify the role of acrylamide intake in ER+?breast cancer etiology. METHODS:The prospective Netherlands Cohort Study on diet and cancer includes 62,573 women, aged 55-69 years. At baseline, a random subcohort of 2589 women was sampled from the total cohort for a case-cohort analysis approach. Dietary acrylamide intake of subcohort members (n?=?1449) and ER+?breast cancer cases (n?=?844) was assessed with a food frequency questionnaire. We genotyped single nucleotide polymorphisms (SNPs) in genes in acrylamide metabolism, sex steroid systems, oxidative stress and DNA repair. Multiplicative interaction between acrylamide intake and SNPs was assessed with Cox proportional hazards analysis, based on 20.3 years of follow-up. RESULTS:Unexpectedly, there was a statistically non-significant inverse association between acrylamide and ER+?breast cancer risk among all women but with no clear dose-response relationship, and no association among never smokers. Among the results for 57 SNPs and 2 gene deletions, rs1056827 in CYP1B1, rs2959008 and rs7173655 in CYP11A1, the GSTT1 gene deletion, and rs1052133 in hOGG1 showed a statistically significant interaction with acrylamide intake for ER+?breast cancer risk. CONCLUSIONS:This study did not provide evidence for a positive association between acrylamide intake and ER+?breast cancer risk. If anything, acrylamide was associated with a decreased ER+?breast cancer risk. The interaction with SNPs in CYP1B1 and CYP11A1 suggests that acrylamide may influence ER+?breast cancer risk through sex hormone pathways.

SUBMITTER: Hogervorst JGF

PROVIDER: S-EPMC6499753 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Interaction between dietary acrylamide intake and genetic variants for estrogen receptor-positive breast cancer risk.

Hogervorst Janneke G F JGF van den Brandt Piet A PA Godschalk Roger W L RWL van Schooten Frederik-Jan FJ Schouten Leo J LJ

European journal of nutrition 20180214 3

<h4>Purpose</h4>The association between dietary acrylamide intake and estrogen receptor-positive (ER+) breast cancer risk in epidemiological studies is inconsistent. By analyzing gene-acrylamide interactions for ER+ breast cancer risk, we aimed to clarify the role of acrylamide intake in ER+ breast cancer etiology.<h4>Methods</h4>The prospective Netherlands Cohort Study on diet and cancer includes 62,573 women, aged 55-69 years. At baseline, a random subcohort of 2589 women was sampled from the ...[more]

PMID: 29445914

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Project description:Over the past decade, hundreds of genome-wide association studies (GWAS) have implicated genetic variants in various diseases, including cancer. However, only a few of these variants have been functionally characterized to date, mainly because the majority of the variants reside in non-coding regions of the human genome with unknown function. A comprehensive functional annotation of the candidate variants is thus necessary to fill the gap between the correlative findings of GWAS and the development of therapeutic strategies. By integrating large-scale multi-omics datasets such as the Cancer Genome Atlas (TCGA) and the Encyclopedia of DNA Elements (ENCODE), we performed multivariate linear regression analysis of expression quantitative trait loci, sequence permutation test of transcription factor binding perturbation, and modeling of three-dimensional chromatin interactions to analyze the potential molecular functions of 2,813 single nucleotide variants in 93 genomic loci associated with estrogen receptor-positive breast cancer. To facilitate rapid progress in functional genomics of breast cancer, we have created "Analysis of Breast Cancer GWAS" (ABC-GWAS), an interactive database of functional annotation of estrogen receptor-positive breast cancer GWAS variants. Our resource includes expression quantitative trait loci, long-range chromatin interaction predictions, and transcription factor binding motif analyses to prioritize putative target genes, causal variants, and transcription factors. An embedded genome browser also facilitates convenient visualization of the GWAS loci in genomic and epigenomic context. ABC-GWAS provides an interactive visual summary of comprehensive functional characterization of estrogen receptor-positive breast cancer variants. The web resource will be useful to both computational and experimental biologists who wish to generate and test their hypotheses regarding the genetic susceptibility, etiology, and carcinogenesis of breast cancer. ABC-GWAS can also be used as a user-friendly educational resource for teaching functional genomics. ABC-GWAS is available at http://education.knoweng.org/abc-gwas/.

Dataset Information

Interaction between dietary acrylamide intake and genetic variants for estrogen receptor-positive breast cancer risk.

Publications

Interaction between dietary acrylamide intake and genetic variants for estrogen receptor-positive breast cancer risk.

Similar Datasets

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