Interaction of breast cancer-relevant DNA repair genes and air pollution in relation to breast cancer risk in UK biobank.

Abstract

We investigated if selected polymorphisms in DNA repair genes modify the association between exposure to particulate matter ≤ 10 micron in diameter (PM₁₀) and breast cancer (BCa) risk. We included 150,929 postmenopausal women (5,969 with BCa) from UK Biobank, a population-based prospective cohort. Cancer diagnoses were ascertained through the linkage to the UK National Health Service Central Registers. Information on BCa risk factors was collected at baseline. Blood samples were collected from participants at enrollment and genotyped using the Applied Biosystems UK BiLEVE Axiom Array or the Applied Biosystems UK Biobank Axiom Array. Cox proportional hazards regression was used to examine interactions of exposure (2007 PM₁₀ and cumulative average PM₁₀) with 14 SNPs, adjusting for BCa risk factors. The positive associations of 2007 PM₁₀ and cumulative average PM₁₀ with BCa risk were stronger in women with one or two copies of XRCC2 rs3218536 C allele vs. none (2007 PM₁₀ Hazard Ratio [HR] per 10 µg/m³ = 1.54, 95% Confidence Interval [CI] 1.22, 1.95 or HR = 1.14, 95% CI 1.03, 1.30 vs. HR = 0.52, 95% CI 0.16, 1.75, p-interaction = 0.02; cumulative average PM₁₀ HR per 10 µg/m³ = 2.80, 95% CI 1.99, 3.96 or HR = 1.89, 95% CI 1.64, 2.18 vs. HR = 0.45, 95% CI 0.08, 2.37, p-interaction = 0.05). We observed no interactions of PM₁₀ with other SNPs. Our results suggest stronger associations of 2007 PM₁₀ and cumulative average PM₁₀ with postmenopausal BCa risk in carriers of XRCC2 rs3218536 C allele.