Analysis of Genetic Variation in Circadian Rhythm Genes and Risk of Ovarian Cancer.

Abstract BackgroundDisruption in biological clock due to genetic variations is associated with increased occurrence of cancers such as breast, ovary, prostate, gastrointestinal and hematological malignancies. Circadian rhythm genes regulate the process of ovulation in the ovaries and are highly expressed in ovarian tumors; whereas disturbance in the circadian rhythm pathway is significantly associated with causative risk factors (i.e. endometriosis, PCOS, etc.) of ovarian cancer. Nevertheless, very few studies have been conducted till date where candidate SNPs of circadian rhythm genes proved as the main prognosticators of ovarian cancer risk and intrusiveness. The main purpose of this study was to investigate some common single nucleotide polymorphisms (SNPs) in circadian rhythm genes (rs475715 of BMAL1/ARNTL, rs1026071, and rs228644 of PER3, rs3792152 of REV1, and rs7302060 of TIMELESS) as causative markers of ovarian cancer risk of in the population of Jammu and Kashmir in India. ResultsOur study included a total of 600 samples (200 cases and 400 age and sex-matched controls). Analysis of the genotype data from the selected SNPs indicated most significant association of rs3792152 of REV1 (OR=1.6, with 95% CI=0.12-1.2, p=0.0003) and rs4757151 of BMAL1/ARNTL (OR=1.847, with 95% CI=1.406-2.426, p=9.15E-06) with the ovarian cancer. The functional putative analysis revealed a significant regulatory effect of both these variants on other genes. ConclusionThese results suggest that some SNPs in circadian rhythm genes, particularly BMAL1/ARNTL and REV1, might be associated with the risk of ovarian cancer in the J&K population of North India.