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Comparative Study
. 2003 Aug 18;89(4):691-6.
doi: 10.1038/sj.bjc.6601075.

Role of genetic polymorphisms of the RNASEL gene on familial prostate cancer risk in a Japanese population

H Nakazato  1 , K Suzuki, H Matsui, N Ohtake, S Nakata, H Yamanaka
Affiliations
Comparative Study

Role of genetic polymorphisms of the RNASEL gene on familial prostate cancer risk in a Japanese population

H Nakazato et al. Br J Cancer. .

Abstract

The RNASEL gene on chromosome 1q25 has been identified as a prostate cancer susceptibility gene. We screened for RNASEL germline mutations in familial prostate cancer patients, and performed a case-control study to examine the association of specific variants with prostate cancer risk in the Japanese. Three variants within the RNASEL gene, G282A, G1385A and T1623G were identified. G1385 and T1623G variants result in previously reported Arg462Gln and Asp541Glu variants, respectively. The novel G282A variant does not cause amino-acid substitution. A case-control study consisting of 101 familial prostate cancer cases and 105 noncancer controls showed that the Gln/Gln genotype of codon462 was observed in 7.6% of controls. However, the Gln/Gln genotype was not observed in cases, and reduced prostate cancer risk (odds ratio (OR)=0.061, P=0.014). The Asp/Asp genotype of codon541 increased the familial prostate cancer risk (OR=7.37, P=0.0004). In subset analysis, a significant association was observed in patients with more than two affected members (OR=3.15, P=0.028), and weak associations were found in patients with metastatic disease (OR=2.40, P=0.11) and high-grade disease (Gleason score >or=7) (OR=3.07, P=0.14). These findings suggested that the polymorphic changes within the RNASEL gene may be associated with familial prostate cancer risk in a Japanese population.

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Figures

Figure 1
Figure 1
Detection of G282A mutation of the RNASEL gene. (I) An aberrant pattern of SSCP was observed in F-60. The pattern of F-59, the affected brother of F-60, was normal. (II) Direct sequencing showed G/A heterozygous pattern of G282A in F-60. Wild-type G/G genotype was observed in F-59.
Figure 2
Figure 2
Detection of G1385A mutation of the RNASEL gene. (I) Three patterns were observed by SSCP analysis (A–C). (II) Direct sequencing showed G/G, G/A and A/A corresponding to A, B and C, respectively.
Figure 3
Figure 3
Detection of G1623 T mutation of the RNASEL gene. (I) Three patterns were observed in the analysis (A–C). (II) Direct sequencing showed C/C, C/A and A/A corresponding to A, B and C, respectively. Note that the sequences appearing in the figures are reverse complement due to using the reverse primer for sequencing.
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