At the gene level, we observed significant associations between all prostate cancer and NPAS2 and PER1 after correcting for multiple testing, while only RORA was significant for aggressive tumors.
A single nucleotide polymorphism of the neuronal PAS domain protein 2 (<i>NPAS2</i>) gene (rs6542993 A>T) was found to be associated with a significantly higher risk of disease progression in both localized (<i>P</i> = 0.001) and advanced (<i>P</i> = 0.039) prostate cancer cases.
Our results showed that at least one SNP in nine core circadian genes (rs885747 and rs2289591 in PER1; rs7602358 in PER2; rs1012477 in PER3; rs1534891 in CSNK1E; rs12315175 in CRY1; rs2292912 in CRY2; rs7950226 in ARNTL; rs11133373 in CLOCK; and rs1369481, rs895521, and rs17024926 in NPAS2) was significantly associated with susceptibility to prostate cancer (either overall risk or risk of aggressive disease), and the risk estimate for four SNPs in three genes (rs885747 and rs2289591 in PER1, rs1012477 in PER3, and rs11133373 in CLOCK) varied by disease aggressiveness.
In contrast, among men with less IR, the NPAS2-variant A allele was associated with decreased prostate cancer risk (odds ratio=0.5, 95% CI, 0.3-1.0) as compared to the GG genotype.