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Title: Genetic polymorphisms of diabetes-related genes, their interaction with diabetes status, and breast cancer incidence and mortality: The Long Island Breast Cancer Study Project.

Authors: Parada Jr, Humberto; Cleveland, Rebecca J; North, Kari E; Stevens, June; Teitelbaum, Susan L; Neugut, Alfred I; Santella, Regina M; Martinez, Maria E; Gammon, Marilie D

Published In Mol Carcinog, (2019 03)

Abstract: To examine 143 diabetes risk single nucleotide polymorphisms (SNPs), identified from genome-wide association studies, in association with breast cancer (BC) incidence and subsequent mortality. A population-based sample of Caucasian women with first primary invasive BC (n = 817) and controls (n = 1021) were interviewed to assess diabetes status. Using the National Death Index, women with BC were followed for >18 years during which 340 deaths occurred (139 BC deaths). Genotyping was done using DNA extracted from blood samples. We used unconditional logistic regression to estimate age-adjusted odds ratios and 95% confidence intervals (CIs) for BC incidence, and Cox regression to estimate age-adjusted hazard ratios and CIs for all-cause and BC-specific mortality. Twelve SNPs were associated with BC risk in additive genotype models, at α = 0.05. The top three significant SNPs included SLC30A8-rs4876369 (P = 0.0034), HHEX-rs11187146 (P = 0.0086), and CDKN2A/CDKN2B-rs1333049 (P = 0.0094). Diabetes status modified the associations between rs4876369 and rs2241745 and BC incidence, on the multiplicative interaction scale. Six SNPs were associated with all-cause (CDKAL1-rs981042, P = 0.0032; HHEX-rs1111875, P = 0.0361; and INSR-rs919275, P = 0.0488) or BC-specific (CDKN2A/CDKN2B-rs3218020, P = 0.0225; CDKAL1-rs981042, P = 0.0246; and TCF2/HNF1B-rs3094508, P = 0.0344) mortality in additive genotype models, at α = 0.05. Genetic polymorphisms that increase the risk of developing diabetes may also increase the risk of developing and dying from BC.

PubMed ID: 30457165 Exiting the NIEHS site

MeSH Terms: Adult; Aged; Aged, 80 and over; Biomarkers/analysis*; Breast Neoplasms/epidemiology*; Breast Neoplasms/genetics; Breast Neoplasms/mortality*; Case-Control Studies; Diabetes Mellitus/genetics*; Female; Follow-Up Studies; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; Incidence; Middle Aged; Polymorphism, Single Nucleotide*; Prognosis; Survival Rate; Young Adult

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