MTNR1A Promoter Methylation is Associated with Increased Breast Cancer Risk

Shift work, particularly, night work has been classified as a
probable carcinogen to humans based on the increased risk
observed in epidemiological studies for some cancer types,
including female breast cancer. The underlying molecular
mechanisms are not well established, but may involve
aberrant epigenetic modifications. Here, effects of changes
in methylation status of 5-methyl cytosine in melatonin and
female hormone receptor genes were investigated as
possible mechanisms for increased breast cancer risk in
female night shift workers. Methylation in promoter regions
of the MTNR1A, MTNR1B, PGR, ESR1 and ESR2 genes
was analyzed by pyrosequencing in a nested case-control
study of female nurses, including 354 breast cancer cases
and 356 healthy controls. The effects of methylation as well
as the combined effects of methylation and shift work on
breast cancer risk were assessed. We demonstrate that
increased methylation of the MTNR1A promoter is
associated with increased risk of breast cancer (OR=1.13,
95% CI: 1.02 -1.24, P=0.019). No association between promoter methylation levels and breast cancer risk was
observed for the other receptor genes investigated.
Furthermore, MTNR1A methylation levels were not affected
by shift work. Altogether, our data suggest that epigenetic
regulation of MTNR1A may contribute to breast cancer.