Metal Exposure and Breast Cancer Among Northern Mexican Women: Assessment of Genetic Susceptibility

This study aims to assess breast cancer (BC) association with metals and whether polymorphisms in CYP1A1, CYP1B1, GSTM1 and GSTT1 act as confounders or as modifiers of those relationships. We performed a secondary analysis of 499 histologically confirmed BC cases and the same number of age-matched population controls. We measured urinary concentrations of 18 metals with mass spectrometry. We determined the genetic variants of interest by allelic discrimination and multiplex PCR. After adjusting for covariates, we found BC negatively associated with arsenic, barium, cobalt, copper, magnesium, molybdenum and vanadium concentrations and positively with those of caesium, manganese, tin and thallium. Most associations remained after stratifying by the genetic variants. We identified that polymorphisms in CYP1B1, CYP1A1 and GSTM1 genes interacted with some metals on BC: interaction p-values CYP1B1 G119T × antimony= 0.036, CYP1B1 G119T × cobalt <0.001, CYP1B1 G119T × tin= 0.032, CYP1A1 A4889G × aluminium= 0.018, CYP1A1 A4889G × arsenic= 0.031, CYP1A1 A4889G × nickel= 0.036, CYP1A1 A4889G × vanadium= 0.031 and GSTM1 deletion × barium= 0.035. Exposure to various individual metals, along with genetic characteristics may contribute to BC development. Further studies are warranted to confirm our results.