Mismatch repair gene MSH3 polymorphism is associated with the risk of sporadic prostate cancer.
OBJECTIVE
The mismatch repair system is a DNA repair mechanism that corrects mispaired bases during DNA replication errors. Cancer cells deficient in MMR proteins have a 10(2) to 10(3)-fold increase in the mutation rate. Single nucleotide polymorphisms of mismatch repair genes have been shown to cause a decrease in DNA repair activity. We hypothesized that mismatch repair gene polymorphism could be a risk factor for prostate cancer and p53 Pro/Pro genotype carriers could influence MSH3 and MSH6 polymorphisms.


METHODS
DNA samples from 110 patients with prostate cancer and 110 healthy controls were analyzed by single strand conformational polymorphism and polymerase chain reaction-restriction fragment length polymorphism to determine the genotypic frequency of 5 polymorphic loci on 2 MMR genes (MSH3 and MSH6) and p53 codon72. The chi-square test was applied to compare genotype frequency between patients and controls.


RESULTS
A significant increase in the G/A+A/A genotype of MSH3 Pro222Pro was observed in patients compared to controls (OR 1.87, 95% CI 1.0-3.5). The frequency of A/G + G/G genotypes of MSH3 exon23 Thr1036Ala also tended to increase in patients (OR 1.57, 95% CI 0.92-2.72). In p53 codon72 Arg/Pro + Pro/Pro carriers the frequency of the AG + GG genotype of MSH3 exon23 was significantly increased in patients compared to controls (OR 2.1, 95% CI 1.05-4.34).


CONCLUSIONS
To our knowledge this is the first report of the association of MSH3 gene polymorphisms in prostate cancer. These results suggest that the MSH3 polymorphism may be a risk factor for prostate cancer.
Hirata
Hiroshi
H
Department of Urology, Veterans Affairs Medical Center and University of California at San Francisco, San Francisco, California 94121, USA.
Hinoda
Yuji
Y
Kawamoto
Ken
K
Kikuno
Nobuyuki
N
Suehiro
Yutaka
Y
Okayama
Naoko
N
Tanaka
Yuichiro
Y
Dahiya
Rajvir
R
D000368:Aged; D020137:Base Pair Mismatch; D053843:DNA Mismatch Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D000074081:MutS Homolog 3 Protein; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D011471:Prostatic Neoplasms / Q000235:genetics*
D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; D005819:Genetic Markers; C078444:MSH3 protein, human; D000074081:MutS Homolog 3 Protein