Overexpression of hMTH in peripheral lymphocytes and risk of prostate cancer: a case‐control analysis

Abstract

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.

MYH mutations are rare in prostate cancer

“…It is likely that aberrant expression rather than mutations of base-excision repair pathway genes contribute to carcinogenesis. Indeed overexpression of MTH, but not MYH, was observed in peripheral lymphocytes of prostate cancer patients when compared to control population (Liu et al 2003). Examination of involvement of other BER pathway genes in prostate cancer is warranted which will help to elucidate molecular mechanisms underlying prostate cancer development as well as to better deWne prostate cancer risk at the population level.…”

Methylation and Messenger RNA Expression of p15INK4b but Not p16INK4a Are Independent Risk Factors for Ovarian Cancer

“…Whether these epigenetic events play a role in the prognosis of epithelial ovarian cancer warrants further investigations (4,25).…”

“…Reverse transcription-PCR was done by using the TaqMan One-Step Reverse Transcriptase-PCR Master Mix Reagents with an ABI PRISM 7700 Sequence Detection System according to the protocol of the manufacturer (Perkin-Elmer Applied Biosystems). The system detects the fluorescence emitted from the fluorogenic oligonucleotide probes, and the signal is directly proportional to the number of template molecules in the reaction mixture after they have crossed a fluorescence detection threshold (25). The ABI PRISM 7700 Sequence Detector is a thermal cycler designed to monitor multiple fluorescent signals in a 96-well format.…”

Single Nucleotide Polymorphisms in DNA Repair Genes and Prostate Cancer Risk

“…Among 40 studies obtained from the search phrases "DNA repair” AND “prostate cancer" AND “polymorphism”, 11 epidemiological studies were included after review of the articles [10–20]. Among twelve additional epidemiological studies which were obtained after searching by single DNA repair gene name AND “prostate cancer”, five studies were excluded because they reported associations between phenotypes, such as expressions or activities of DNA enzymes and prostate cancer risk [21–25]. The remaining six studies also were included in this manuscript [26–31].…”