Nakazato H, Suzuki K, Matsui H, Ohtake N, Nakata S, Yamanaka H
Department of Urology, Gunma University School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma, 3718511, Japan.
Br J Cancer. 2003 Aug 18;89(4):691-6. doi: 10.1038/sj.bjc.6601075.
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.
位于1号染色体1q25上的RNASEL基因已被确定为前列腺癌易感基因。我们在家族性前列腺癌患者中筛查了RNASEL种系突变，并进行了一项病例对照研究，以检验日本人群中特定变异与前列腺癌风险的关联。在RNASEL基因中鉴定出三个变异，即G282A、G1385A和T1623G。G1385和T1623G变异分别导致先前报道的Arg462Gln和Asp541Glu变异。新发现的G282A变异不会引起氨基酸替换。一项由101例家族性前列腺癌病例和105例非癌症对照组成的病例对照研究表明，密码子462的Gln/Gln基因型在7.6%的对照中被观察到。然而，在病例中未观察到Gln/Gln基因型，且前列腺癌风险降低（优势比（OR）=0.061，P=0.014）。密码子541的Asp/Asp基因型增加了家族性前列腺癌风险（OR=7.37，P=0.0004）。在亚组分析中，在有两个以上患病成员的患者中观察到显著关联（OR=3.15，P=0.028），在转移性疾病患者（OR=2.40，P=0.11）和高级别疾病患者（Gleason评分≥7）（OR=3.07，P=0.14）中发现了弱关联。这些发现表明，RNASEL基因内的多态性变化可能与日本人群中的家族性前列腺癌风险相关。
