RNASEL G1385A variant and breast cancer susceptibility

Abstract

RNASEL (MIM# 180435) encodes for the ubiquitously expressed ribonuclease L (RNase L), which mediates the antiviral and pro-apoptotic activities of the 2-5A system. Recently, RNASEL Arg462Gln (G1385A) variant is shown to be implicated in up to 13% of prostate cancer cases. Furthermore, RNASEL mutations segregating with disease within hereditary prostate cancer (HPC) families, and loss of heterozygosity (LOH) in tumor tissues have been reported. RNase L has been proposed to suppress the development of cancer through its ability to degrade RNA and initiate a cellular stress that leads to apoptosis. Analysis for allelic losses at the long arm of the chromosome 1 suggested that inactivation of a gene(s) on 1q23-32, which encompasses the RNASEL locus, might contribute to the genesis of breast cancer. Based on chromosomal location and function of RNASEL, and pleitropic effects of cancer associated mutations, we south to investigate the hypothesis that Arg462Gln variant of RNASEL is associated with breast cancer risk. The homozygote mutant (odds ratio (OR) = 0.75, 95% CI= 0.49- 1.14), heterozygote (OR=1.02, 95% CI= 0.76-1.37), or the genotype having at least one mutant allele (OR= 0.94, 95% CI=0.72-1.24) was found to be not associated with the breast cancer risk. The adjustment of the data with age, menopausal, smoking status, body-mass-index, age at menarche, age of 1st pregnancy, number of children, and family history of breast cancer did not change the results (homozygote mutant (OR= 0.72, 95% CI= 0.46-1.12), heterozygote (OR= 0.95, 95% CI= 0.70-1.29), or genotype having at least one mutant allele (OR= 0.89, 95% CI= 0.66-1.18)). In conclusion, our study reports no association between the RNASEL G1385A variant and breast cancer risk.