Objectives: Prostate cancer (PC) varies widely by geographic location and ethnicity. American men have a high PC risk but most have localized disease. In contrast, Asian Indians have a low PC risk but most are diagnosed with metastatic disease. Epidemiological and genetic data suggest an important role of genetic susceptibility in PC. Most studies were performed in whites. Substantially less is known about gene variation-associated PC in low-risk populations. The objective of this study was to investigate the role of RNASEL and MSR1 in Asian-Indian men with advanced PC.

Methods: We genotyped DNA samples obtained from 113 cases and 245 age-matched controls (Northern India).

Results: For RNASEL, we identified 8 variants (7 novel and 1 previously published, D541E), including 4 exonic, 3 intronic, and 1 change in the 3'-noncoding region. Of these, we detected a novel 4-bp truncation mutation (Val51ArgfsX2) in 2 controls. For MSR1, we identified 4 novel variants (2 intronic and 2 exonic) and 2 previously reported variants (P275A and promoter -4,637 A>G). We also genotyped 3 common MSR1 variations (promoter -14,742 A>G, IVS5-59 C>A, and IVS7 delinsTTA). We found no associations among any of the sequence variations and PC. Three major haplotypes account for most of all MSR1 haplotypes in Asian Indians. Haplotype frequencies were not significantly different between cases and controls.

Conclusions: Our results do not support a role for RNASEL, or MSR1 mutations in advanced Asian-Indian PC. This study warrants additional investigations of these genes in etiology particularly among individuals from diverse ethnic and geographic groups.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2700292PMC
http://dx.doi.org/10.1016/j.urology.2007.11.139DOI Listing

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