Polycyclic aromatic hydrocarbons and breast cancer: Effect measure modification by vitamin D and vitamin D-related single nucleotide polymorphisms

Abstract Purpose: Our objective was to examine whether vitamin D and vitamin D-related SNPs modify the association between individual PAH sources and breast cancer . Methods: This population-based case-control study included 1,026 women with first primary in situ or invasive breast cancer and 1,074 age-frequency matched controls. To evaluate effect measure modification (EMM) by measured vitamin D and vitamin D-related single nucleotide polymorphisms on multiple PAH measures (active cigarette smoking, smoking spouse, grilled/smoked meat consumption, synthetic log use, and vehicular traffic), we estimated odds ratios and 95% confidence intervals with unconditional logistic regression. EMM was assessed on the multiplicative (likelihood ratio tests) and additive scales (interaction contrast ratio). Results: Vitamin D modified the synthetic log use breast cancer association on the additive scale (ICR= -0.86; 95% CI: -1.67, -0.04) and multiplicative scales (OR=0.52; 95% CI: 0.09, 0.94). Contrary to expectation, the stratum-specific OR for synthetic log use among those with vitamin D <30 ng/mL was below the null compared to the elevated OR found for those with vitamin D ≥ 30ng/mL (0.89 vs 1.70). The effect estimates for other PAHs were imprecise. Conclusion: We found evidence of EMM for the association between synthetic log use and breast cancer by vitamin D. The pattern of association was unexpected and requires replication. Potential EMM was observed with several other PAH measures. Additionally, we observed EMM for several SNPs which were not statistically significant after adjustment for multiple comparisons.