Polymorphisms of MLH1 in benign prostatic hyperplasia and sporadic prostate cancer.
Mismatch repair is one of several DNA repair pathways of which defects may lead to cancer. We hypothesize that polymorphisms of the MLH1 gene can be a risk factor for benign prostatic hyperplasia (BPH) and prostate cancer. The genetic distribution of MLH1 polymorphisms that lead to amino acid changes at codons 132, 219, 384, and 723 were analyzed in BPH and sporadic prostate cancer patients, and compared to healthy controls from an Asian population. These experiments demonstrate a protective role for the codon 384 variant allele against prostate cancer (P=0.031) but not BPH when compared to normal controls and furthermore, an inverse association was observed with stage (P=0.074) and grade (P=0.056) of cancer. This is the first report that demonstrates a protective effect for the race-related MLH1 polymorphism at codon 384 against prostate cancer and these results are important in understanding their role in this disease.
Tanaka
Yuichiro
Y
Department of Surgery/Urology (112F), Veterans Affairs Medical Center, University of California, 4150 Clement St., San Francisco, CA 94121, USA. Yuichiro.tanaka@ucsf.edu
Zaman
Mohd S
MS
Majid
Shahana
S
Liu
Jan
J
Kawakami
Kazumori
K
Shiina
Hiroaki
H
Tokizane
Takashi
T
Dahiya
Angela V
AV
Sen
Saunak
S
Nakajima
Koichi
K
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000368:Aged; D019943:Amino Acid Substitution; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011470:Prostatic Hyperplasia / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1