This report implicates variants in RNASEL, including this variant, in causing hereditary prostate cancer type I. The study describes combining data from 91 families to perform linkage analysis — results implicated several prostate susceptibility loci, including this one. (No statistical significance is given, the authors write it “suggests HPC1 maps to [this region]”.)
This variant was seen in one of 26 families, 8 of which were selected on the basis of apparent linkage and shared haplotypes in this region. The variant segregates with disease in the four brothers studied, but this is expected as the family was selected for sequencing on the basis of shared haplotypes.
Unaffected white males, unrelated CEPH samples (HapMap), and US population controls had this variant heterozygously in 3 individuals out of 330 (3 out of 660 alleles). They also studied 258 sporadic (non-hereditary) prostate cancer cases and found the variant heterozygously in two individuals. This seems to contradict a pathogenic hypothesis; the authors comment “as yet we cannot identify a difference in allele frequency between affected individuals and controls.”
Functional analysis of the variant found that cell lines carrying this variant heterozygously have half the RNAse L enzyme activity compared to wild-type cells.