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N2 Variations in RNASEL, MSR1 and E-cadherin genes and prostate cancer in Poland

      Introduction and Objectives

      In most developed countries, prostate cancer (PC) is the most frequently diagnosed malignancy in men. A positive family history is among the strongest epidemiological risk factors for prostate cancer. Linkage studies of PC families revealed numerous PC susceptibility chromosomal loci, but to date no major highrisk gene has been identified. Three genes, RNASEL, MSR1 and E-cadherin, have been previously implicated in PC pathogenesis. RNASEL (ribonuclease L), has been identified as a candidate PC susceptibility gene from a family-based approach in hereditary prostate cancer 1 (HPC1) locus. MSR1 (Macrophage Scavenger Receptor 1) is a gene within a region of linkage on chromosome 8p. The prevalence of five MSR1 common variants in PC cases of European- and African-American descent was reported to be higher compared with unaffected men. E-cadherin is the gene for early-onset familial gastric cancer. Polymorphisms in E-cadherin have been suggested to confer increased risk of PC. The most extensively studied variant, the −160C 1 A promoter polymorphisms, has been associated with increased PC risk in the Netherlands, Sweden and USA. To date, the roles of mutations in these genes in PC etiology in Slavic populations have not been investigated.
      We investigated whether inherited variations in RNASEL, MSR1 and E-cadherin genes contribute to PC risk in Poland.

      Material and Methods

      737 PC cases were collected from hospitals in Szczecin and surrounding counties. The mean age of diagnosis was 67.3 years (range 43–92). Family histories were obtained from each subject. 110 patients (15%) had one or more first- or second-degree relatives with PC (familial cases). The control group consisted of 511 unselected healthy men aged 50 and above, taken from three family doctors practicing in Szczecin. None of the controls had cancer.The polymorphisms in MSR1 and RNASEL were selected after sequencing of the entire coding region of these genes in 52 and 94 Polish men with familial PC, respectively. We also sequenced the entire coding sequence of E-cadherin gene in 89 individuals with diffuse gastric cancer. Five common DNA variants (R462Q and D541E in RNASEL, R293X and P275A in MSR1, and 2076C>T in E-cadherin) were found. These five variants and the −160C>A promoter change in E-cadherin were then genotyped in all PC cases and controls by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR). The frequencies of the DNA variants were compared in cases and controls. The ORs were used as estimates of relative risk.

      Results

      The frequencies of genotyped variants in MSR1, RNASEL and E-cadherin genes in cases and controls were similar. We did not observed any association for the studied variants when cases were stratified by age of diagnosis, family history, PSA, Gleason score and tumor stage.

      Conclusions

      Inherited variation in RNASEL, MSR1 and E-cadherin genes do not seem to contribute to PC development in Poland.