MNS16A tandem repeat minisatellite of human telomerase gene and prostate cancer susceptibility

Abstract

Telomere dysfunction is an early event in the development of prostate cancer and telomerase (TERT) activity is detectable in the majority of prostate cancers. Genetic variation in TERT and its regulatory elements may influence prostate carcinogenesis. MNS16A, a functional polymorphic tandem repeat minisatellite of TERT, has been studied in several malignancies. We determined MNS16A genotypes in an Austrian case-control study for the first time in the context of prostate cancer, comprising 1165 prostate cancer cases and 674 benign prostate hyperplasia controls with PCR. In addition to the five reported variable number of tandem repeats (VNTRs), we identified VNTR-212, a rare variant, for the first time in a European population. Multiple logistic regression analysis revealed no differences in genotype distribution between cases and controls. However, in stratified analysis, MNS16A VNTR-274 (OR = 0.25, 95% CI = 0.06-0.79, P = 0.016) and genotype 274/302 (OR = 0.13, 95% CI = 0.01-0.58, P = 0.005) were associated with a significantly decreased risk of prostate cancer in the age group >70 years. Our finding of a MNS16A genotype conferring a protective effect against prostate cancer in older men suggests a potential role of this polymorphism in prostate cancer susceptibility but demands to be validated in further studies.

Association of human telomerase reverse transcriptase gene polymorphisms, serum levels, and telomere length with renal cell carcinoma risk and pathology

“…The polymorphic number of tandem repeats of MNS16A has been associated with telomerase activity, and subsequently with the risk for several malignancies. In this regard, long MNS16A alleles decrease the risk for glioma, colorectal, and breast cancer , while they increase the risk for nasopharyngeal carcinoma, prostate, and lung cancer . In addition to MNS16A , several additional genetic variations of the hTERT gene have been associated with cancer risk and progression.…”

MNS16A tandem repeat minisatellite of human telomerase gene: functional studies in colorectal, lung and prostate cancer

“…Increased risk of lung cancer was associated with longer alleles in an US hospital-based pilot scale study [11] but with the short VNTR-243 in a Korean study [21]. In our Austrian prostate cancer study [13], VNTR-274 was ascribed a protective effect in Caucasian males older than 70 years in stratified analysis, but no overall association with disease risk was observed. Furthermore, we investigated MNS16A genotypes in a Caucasian colorectal cancer cohort, reporting VNTR-274 as risk allele [12].…”

“…Genotypes of MNS16A, a functional polymorphic tandem repeat minisatellite of TERT locus, have been investigated in cancers of the brain [14–16], breast [17–19], lung [11, 20, 21], colorectum [12], nasopharynx [22], prostate [13], blood [23], and kidney [24]. Furthermore, two meta-analyses of MNS16A were published so far [25, 26].…”

“…For cloning of size-selected MNS16A PCR products [12, 13], TOPO TA Cloning Kit (Invitrogen, Carlsbad, CA, USA) containing pCRII-TOPO vector was used as described by the manufacturer. MNS16A VNTRs (−212, −243, −274, −302, −333, −364), excised from pCRII-TOPO were inserted into pGL3-basic vector (Promega, Madison, WI, USA) using Rapid DNA Ligation Kit (Roche Applied Science, Upper Bavaria, Germany).…”

“…In addition to the four VNTRs reported by Wang et al . (VNTR-243, VNTR-274, VNTR-302, VNTR-333) [11], we identified two novel VNTRs of MNS16A (VNTR-212 and VNTR-364) in case control studies of colorectal cancer [12] and prostate cancer [13]. This prompted us to investigate promoter activity of all known six MNS16A VNTRs in cell lines of colorectal, lung, and prostate cancer.…”