Reduced expression of hMSH2 and hMLH1 and risk of prostate cancer: a case-control study.
BACKGROUND
Although prostate cancer is the most common incident cancer in men, not much is known about its etiology. We tested the hypothesis that expression levels of hMSH2 and hMLH1 in unaffected (normal) tissue play a role in the etiology of prostate cancer.


METHODS
Total RNA was extracted from peripheral blood lymphocytes of subjects ascertained by a case-control study (70 patients and 97 age- and ethnicity-matched controls). A multiplex reverse transcription-polymerase chain reaction assay was used to simultaneously evaluate the relative expression of hMSH2 and hMLH1, using beta-actin as the internal control.


RESULTS
The relative gene expression levels of hMSH2 and hMLH1 were significantly lower in cases than in controls (P < 0.05 for both genes). When compared with the highest tertile of the controls, low expression levels (the middle and lowest tertiles) of hMLH1 were associated with significantly increased risk of prostate cancer in a dose-response relationship (ORs = 2.68, and 4.31; 95% confidence interval = 1.00-7.23 and 1.64-11.30, respectively) after adjustment for age, ethnicity, smoking status, and family history of prostate cancer.


CONCLUSIONS
These results suggest that reduced expression of hMLH1 in peripheral lymphocytes may be a risk factor for prostate cancer. However, it cannot be ruled out that the reduced expression we observed may be caused by the disease status. Our findings and the factors that may affect the expression of hMLH1 need further confirmation in larger prospective studies.
Strom
S S
SS
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Spitz
M R
MR
Yamamura
Y
Y
Babaian
R J
RJ
Scardino
P T
PT
Wei
Q
Q
D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D000368:Aged; D020137:Base Pair Mismatch; D002352:Carrier Proteins; D016022:Case-Control Studies; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins; D013196:Dihydrotestosterone / Q000097:blood; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism / Q000502:physiology; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009687:Nuclear Proteins; D010865:Pilot Projects; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D013739:Testosterone / Q000097:blood
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D013196:Dihydrotestosterone; D013739:Testosterone; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein