We summarize fifteen epidemiological studies, including five studies on shift work that have indicated BMAL1, BMAL2, CLOCK, NPAS2, CRY1, CRY2, PER1, PER3 and TIMELESS as a candidate breast cancer risk variants.
Circadian (clock) genes have been linked with several functions relevant to cancer, and epidemiologic research has suggested relationships with breast cancer risk for variants in NPAS2, CLOCK, CRY2 and TIMELESS.
We also observed a significant association between stage II, III, and IV breast cancers and TIMELESS promoter hypomethylation in peripheral blood lymphocytes (OR, 0.35; 95% CI, 0.13-0.96) in 80 breast cancer cases and 80 age-matched controls, which is corroborated by documented overexpression of TIMELESS in breast tumor tissue compared to adjacent normal tissue.