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

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 Japanes...

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Bibliographic Details
Published in:British journal of cancer 2003-08, Vol.89 (4), p.691-696
Main Authors: NAKAZATO, H, SUZUKI, K, MATSUI, H, OHTAKE, N, NAKATA, S, YAMANAKA, H
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Alleles
Biological and medical sciences
Case-Control Studies
chromosome 1
Chromosomes, Human, Pair 1 - genetics
Endoribonucleases - genetics
Genetic Predisposition to Disease
Genetics and Genomics
Humans
Japan - epidemiology
Male
Medical sciences
Middle Aged
Mutation - genetics
Nephrology. Urinary tract diseases
Polymerase Chain Reaction
Polymorphism, Genetic
Polymorphism, Single-Stranded Conformational
Prostate - enzymology
Prostatic Neoplasms - enzymology
Prostatic Neoplasms - genetics
RNASEL gene
Tumors of the urinary system
Urinary tract. Prostate gland
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Summary: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.
ISSN:0007-0920
1532-1827
DOI:10.1038/sj.bjc.6601075