Circadian genes and risk of prostate cancer in the prostate cancer prevention trial
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 12, 2018
- Source ID
- 10.1002/mc.22770
Entities
People
- Ann W Hsing
- Ashraful M. Hoque
- Baiyu Yang
- Cathee Till
- Catherine M. Tangen
- Christine Ambrosone
- Ian M. Thompson, Jr.
- Kai Yu
- Lisa W. Chu
- Phyllis J. Goodman
- Robin J Leach
- Summer Han
- Yong Zhu
Organizations
- National Cancer Institute
- Roswell Park Comprehensive Cancer Center
- Stanford Cancer Institute
- The University of Texas MD Anderson Cancer Center
- United States Department of Defense
- University of Texas at Austin
- Yale University