Dataset Information

Interaction between polyunsaturated fatty acids and genetic variants in relation to breast cancer incidence.

ABSTRACT: Higher intake of ?-3 relative to ?-6 polyunsaturated fatty acids (PUFAs) may reduce breast carcinogenesis via different metabolic pathways. The PUFA-breast cancer association remains inconclusive, thus, we hypothesized that interactions between the ratio of dietary ?-3:?-6 intake and polymorphisms from PUFA-related metabolic pathways would help elucidate an association. Utilizing resources from the Long Island Breast Cancer Study Project, a population-based case-control study (n=1035 cases/1075 controls), we examined interactions between ?-3:?-6 ratio and 18 polymorphisms of 15 genes. Compared to the putative lowest risk group (high ?-3:?-6,low-risk FASL rs763110 CT/TT genotype), the odds ratio (OR) for breast cancer from unconditional logistic regression models was weakly increased for other exposure-genotype combinations (high ?-3:?-6,high-risk FASL CC genotype, OR=1.18,95% confidence interval(CI)=0.90,1.53; low ?-3:?-6,CT/TT genotype, OR=1.35,95%CI=1.09,1.66); but was approximately null for the putative highest risk group (low ?-3:?-6,CC genotype; OR=1.06,95%CI=0.81,1.38). We observed an interaction between the ?-3:?-6 ratio and FASL rs763110 on the additive scale [Relative Excess Risk Due to Interaction(RERI)=-0.47, 95%CI=-0.92,-0.02]. Interactions with other polymorphisms considered were not evident. Our findings suggest that the PUFA-breast cancer association may be modified by FASL. However, additional research is needed given this interaction may be due to chance and is inconsistent with our a priori biologic hypothesis.

SUBMITTER: Khankari NK

PROVIDER: S-EPMC5621474 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Interaction between polyunsaturated fatty acids and genetic variants in relation to breast cancer incidence.

Khankari Nikhil K NK Bradshaw Patrick T PT Steck Susan E SE He Ka K Olshan Andrew F AF Ahn Jiyoung J Terry Mary Beth MB Crew Katherine D KD Teitelbaum Susan L SL Neugut Alfred I AI Santella Regina M RM Gammon Marilie D MD

Journal of cancer epidemiology and prevention (iMedPub) 20161230 1

Higher intake of ω-3 relative to ω-6 polyunsaturated fatty acids (PUFAs) may reduce breast carcinogenesis via different metabolic pathways. The PUFA-breast cancer association remains inconclusive, thus, we hypothesized that interactions between the ratio of dietary ω-3:ω-6 intake and polymorphisms from PUFA-related metabolic pathways would help elucidate an association. Utilizing resources from the Long Island Breast Cancer Study Project, a population-based case-control study (n=1035 cases/1075 ...[more]

PMID: 28971183

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Project description:ImportanceAortic stenosis (AS) has no approved medical treatment. Identifying etiological pathways for AS could identify pharmacological targets.ObjectiveTo identify novel genetic loci and pathways associated with AS.Design, setting, and participantsThis genome-wide association study used a case-control design to evaluate 44 703 participants (3469 cases of AS) of self-reported European ancestry from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort (from January 1, 1996, to December 31, 2015). Replication was performed in 7 other cohorts totaling 256 926 participants (5926 cases of AS), with additional analyses performed in 6942 participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Follow-up biomarker analyses with aortic valve calcium (AVC) were also performed. Data were analyzed from May 1, 2017, to December 5, 2019.ExposuresGenetic variants (615 643 variants) and polyunsaturated fatty acids (ω-6 and ω-3) measured in blood samples.Main outcomes and measuresAortic stenosis and aortic valve replacement defined by electronic health records, surgical records, or echocardiography and the presence of AVC measured by computed tomography.ResultsThe mean (SD) age of the 44 703 GERA participants was 69.7 (8.4) years, and 22 019 (49.3%) were men. The rs174547 variant at the FADS1/2 locus was associated with AS (odds ratio [OR] per C allele, 0.88; 95% CI, 0.83-0.93; P = 3.0 × 10-6), with genome-wide significance after meta-analysis with 7 replication cohorts totaling 312 118 individuals (9395 cases of AS) (OR, 0.91; 95% CI, 0.88-0.94; P = 2.5 × 10-8). A consistent association with AVC was also observed (OR, 0.91; 95% CI, 0.83-0.99; P = .03). A higher ratio of arachidonic acid to linoleic acid was associated with AVC (OR per SD of the natural logarithm, 1.19; 95% CI, 1.09-1.30; P = 6.6 × 10-5). In mendelian randomization, increased FADS1 liver expression and arachidonic acid were associated with AS (OR per unit of normalized expression, 1.31 [95% CI, 1.17-1.48; P = 7.4 × 10-6]; OR per 5-percentage point increase in arachidonic acid for AVC, 1.23 [95% CI, 1.01-1.49; P = .04]; OR per 5-percentage point increase in arachidonic acid for AS, 1.08 [95% CI, 1.04-1.13; P = 4.1 × 10-4]).Conclusions and relevanceVariation at the FADS1/2 locus was associated with AS and AVC. Findings from biomarker measurements and mendelian randomization appear to link ω-6 fatty acid biosynthesis to AS, which may represent a therapeutic target.

Dataset Information

Interaction between polyunsaturated fatty acids and genetic variants in relation to breast cancer incidence.

Publications

Interaction between polyunsaturated fatty acids and genetic variants in relation to breast cancer incidence.

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