Overexpression of hMTH in peripheral lymphocytes and risk of prostate cancer: a case-control analysis.
Oxidative damage is an important factor in prostate carcinogenesis, and overexpression of human MutT homolog (hMTH), a repair gene that removes oxidative damage, is a molecular marker of cellular oxidative stress. Therefore, we tested the hypothesis that overexpression of hMTH in unaffected (normal) surrogate tissue is associated with risk of prostate cancer in a pilot study of 51 patients with diagnosed prostate cancer and 50 age- and ethnicity-matched controls. Total RNA was extracted from phytohemagglutinin-stimulated peripheral blood lymphocytes of these subjects. We performed the real-time reverse transcription-polymerase chain reaction assay to evaluate the relative mRNA expression of three oxidative-damage-repair genes, human MutM homolog (hMMH), hMTH, and human MutY homolog (hMYH), with beta-actin and human O(6)-methylguanine DNA methyltransferase (hMGMT) as the internal controls. The relative gene expression levels of hMMH and hMTH were borderline higher in the cases than in controls (15.3% and 28.8% higher, respectively; P = 0.046 and P = 0.035, respectively), whereas no increase was observed for hMYH and hMGMT. With the median of the controls' values as the cutoff point, we observed that a high expression level of hMTH, but not of other genes, was associated with a significantly increased risk of prostate cancer (odds ratio = 2.62; 95% confidence interval = 1.13-6.75) after adjustment for age and ethnicity. These results suggested that increased expression of hMTH in peripheral lymphocytes may be a risk factor for prostate cancer and support our priori hypothesis. Although our findings were biologically plausible and consistent with the literature, they were preliminary and need to be confirmed in larger studies. In addition, a correlation between the expression level of hMTH and the level of oxidative DNA damage in the target tissues needs to be established as well.
Liu
Zhensheng
Z
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Wang
Li-E
LE
Strom
Sara S
SS
Spitz
Margaret R
MR
Babaian
Richard J
RJ
DiGiovanni
John
J
Wei
Qingyi
Q
D000199:Actins / Q000097:blood / Q000235:genetics; D016022:Case-Control Studies; D004249:DNA Damage / Q000235:genetics; D045647:DNA Glycosylases; D045643:DNA Repair Enzymes; D043382:DNA-Formamidopyrimidine Glycosylase; D005786:Gene Expression Regulation; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009699:N-Glycosyl Hydrolases / Q000235:genetics; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics; D018384:Oxidative Stress; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D010835:Phytohemagglutinins / Q000494:pharmacology; D010865:Pilot Projects; D011471:Prostatic Neoplasms / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D012333:RNA, Messenger / Q000097:blood; D012016:Reference Values; D012044:Regression Analysis; D012307:Risk Factors; D013781:Texas / Q000453:epidemiology; D044465:White People / Q000235:genetics
D000199:Actins; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D019853:O(6)-Methylguanine-DNA Methyltransferase; D010744:Phosphoric Monoester Hydrolases; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; C061738:mutY adenine glycosylase; D043382:DNA-Formamidopyrimidine Glycosylase; C078207:8-oxodGTPase; D045643:DNA Repair Enzymes