Tuesday, April 24, 2012

From NCI: TeRT locus polymorphisms and cancer risk

http://www.ncbi.nlm.nih.gov/pubmed/22523397


J Natl Cancer Inst. 2012 Apr 20. [Epub ahead of print]

Telomerase Reverse Transcriptase Locus Polymorphisms and Cancer Risk: A Field Synopsis and Meta-Analysis.

Source

Affiliations of authors: Department of Oncological and Surgical Sciences, Meta-analysis Unit, University of Padova, Padova, Italy (SM, DV, DN);Cancer Research UK Genetic Epidemiology Unit, Department of Public Health and Primary Care, Strangeways Research Laboratory, Cambridge, UK (KAP); Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD (MTL); Division of Population Sciences, Moffitt Cancer Center & Research Institute, Tampa, FL (KME); Department of Pathology, School of Medicine, Cardiff University, Cardiff, UK (DMB); Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (JP, IDV); Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard Medical School, Boston, MA (JP, IDV).

Abstract

Background
Several recent studies have provided evidence that polymorphisms in the telomerase reverse transcriptase (TERT) gene sequence are associated with cancer development, but a comprehensive synopsis is not available. We conducted a systematic review and meta-analysis of the available molecular epidemiology data regarding the association between TERT locus polymorphisms and predisposition to cancer.

Methods
A systematic review of the English literature was conducted by searching PubMed, Embase, Cancerlit, Google Scholar, and ISI Web of Knowledge databases for studies on associations between TERT locus polymorphisms and cancer risk. Random-effects meta-analysis was performed to pool per-allele odds ratios for TERT locus polymorphisms and risk of cancer, and between-study heterogeneity and potential bias sources (eg, publication and chasing bias) were assessed. Because the TERT locus includes the cleft lip and palate transmembrane 1-like (CLPTM1L) gene, which is in linkage disequilibrium with TERT, CLPTM1L polymorphisms were also analyzed. Cumulative evidence for polymorphisms with statistically significant associations was graded as "strong," "moderate," and "weak" according to the Venice criteria. The joint population attributable risk was calculated for polymorphisms with strong evidence of association.

Results
Eighty-five studies enrolling 490 901 subjects and reporting on 494 allelic contrasts were retrieved. Data were available on 67 TERT locus polymorphisms and 24 tumor types, for a total of 221 unique combinations of polymorphisms and cancer types. Upon meta-analysis, a statistically significant association with the risk of any cancer type was found for 22 polymorphisms. Strong, moderate, and weak cumulative evidence for association with at least one tumor type was demonstrated for 11, 9, and 14 polymorphisms, respectively. For lung cancer, which was the most studied tumor type, the estimated joint population attributable risk for three polymorphisms (TERT rs2736100, intergenic rs4635969, and CLPTM1L rs402710) was 41%. Strong evidence for lack of association was identified for five polymorphisms in three tumor types.

Conclusions
To our knowledge, this is the largest collection of data for associations between TERT locus polymorphisms and cancer risk. Our findings support the hypothesis that genetic variability in this genomic region can modulate cancer susceptibility in humans.

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