Circadian genes and risk of prostate cancer in the prostate cancer prevention trial

Circadian genes have been considered as a possible biological mechanism for the observed relationship between circadian rhythm disruptions and increased risk of hormone-related cancers. In the current study, we investigated the relationship between circadian gene variants and prostate cancer risk and whether reducing bioavailable testosterone modifies the circadian genes-prostate cancer relationship. We conducted a nested case-control study among Caucasian men in the Prostate Cancer Prevention Trial (PCPT), a randomized placebo-controlled clinical trial to assess if finasteride (an androgen bioactivation inhibitor) could prevent prostate cancer. We evaluated the associations between 240 circadian gene variations and prostate cancer risk among 1092 biopsy-confirmed prostate cancer cases and 1089 biopsy-negative controls in the study (642 cases and 667 controls from the placebo group; 450 cases and 422 controls from the finasteride group), stratified by treatment group. Among men in the finasteride group, there were suggestive associations between NPAS2 variants and total prostate cancer risk, with one SNP remaining statistically significant after Bonferroni correction (rs746924, odds ratio [OR] = 1.5, P = 9.6 × 10-5 ). However, we found little evidence of increased prostate cancer risk (overall or by low/high grade) associated with circadian gene variations in men of the placebo group, suggesting potential modification of genetic effects by treatment. We did not find strong evidence that circadian gene variants influenced prostate cancer risk in men who were not on finasteride treatment. There were suggestive associations between NPAS2 variants and prostate cancer risk among men using finasteride, which warrants further investigations.

Molecular carcinogenesis. 2018 Jan 10 [Epub ahead of print]

Lisa W Chu, Cathee Till, Baiyu Yang, Catherine M Tangen, Phyllis J Goodman, Kai Yu, Yong Zhu, Summer Han, Ashraful M Hoque, Christine Ambrosone, Ian Thompson, Robin Leach, Ann W Hsing

Formerly Cancer Prevention Institute of California, Fremont, California., SWOG Statistical Center, Seattle, Washington., Stanford Cancer Institute, Stanford School of Medicine, Stanford, California., National Cancer Institute, Bethesda, MaryLand., Yale University, New Haven, Connecticut., MD Anderson Cancer Center, Houston, Texas., Roswell Park Cancer Institute, Buffalo, New York., Formerly University of Texas Health Science Center, San Antonio, Texas.