Genetic variation in five genes important in telomere biology and risk for breast cancer

Abstract

Telomeres, consisting of TTAGGG nucleotide repeats and a protein complex at chromosome ends, are critical for maintaining chromosomal stability. Genomic instability, following telomere crisis, may contribute to breast cancer pathogenesis. Many genes critical in telomere biology have limited nucleotide diversity, thus, single nucleotide polymorphisms (SNPs) in this pathway could contribute to breast cancer risk. In a population-based study of 1995 breast cancer cases and 2296 controls from Poland, 24 SNPs representing common variation in POT1, TEP1, TERF1, TERF2 and TERT were genotyped. We did not identify any significant associations between individual SNPs or haplotypes and breast cancer risk; however, data suggested that three correlated SNPs in TERT (À1381C4T, À244C4T, and Ex2-659G4A) may be associated with reduced risk of breast cancer among individuals with a family history of breast cancer (odds ratios 0.73, 0.66, and 0.57, 95% confidence intervals 0.53 -1.00, 0.46 -0.95 and 0.39 -0.84, respectively). In conclusion, our data do not support substantial overall associations between SNPs in telomere pathway genes and breast cancer risk. Intriguing associations with variants in TERT among women with a family history of breast cancer warrant follow-up in independent studies.

Genetic Variations in TERT-CLPTM1L Genes and Risk of Lung Cancer in a Chinese Population

“…This gene is widely expressed in different tissues; however, its function is largely unknown. Several studies have revealed that the common polymorphisms of CLPTM1L are associated with multiple types of cancers, including lung cancer (Savage et al, 2007;Wang et al, 2008;Gago-Dominguez et al, 2011;Nan et al, 2011). In the most recently published study, Ke et al (2013) confirmed the association between the T allele of rs401681 and reduced risk of lung cancer in a Chinese population.…”

“…CLPTM1L gene encodes a predicted transmembrane protein, but its function is largely unknown. Several studies have reported that the common polymorphisms of CLPTM1L are associated with the risk for development of various cancers, such as bladder cancer, skin cancer, lung cancer, breast cancer (Savage et al 2007;Wang et al, 2008;Gago-Dominguez et al, 2011;Nan et al, 2011).…”

TERT rs2736098 Polymorphism and Cancer Risk: Results of a Meta-analysis

“…In a study of both Asian and European individuals, the TERT rs2736098 polymorphism was identified as a likely contributor to increased risk of developing bladder cancer in individuals of Asian ancestry (Gago-Dominguez et al, 2011). A study based on the European population found that TERT rs2736098 shows a borderline statistically significant association with reduced risk of breast cancer in analysis of all cases and controls; however, the association appeared to be stronger for individuals with a family history of breast cancer (Savage et al, 2007).…”

“…Although several studies in recent years have focused on the association between the TERT rs2736098 polymorphism and cancer susceptibility, the results are inconclusive (Savage et al, 2007;Jin et al, 2009;Liu et al, 2010;Chen et al, 2011;Gago-Dominguez et al, 2011) . Therefore, this meta-analysis was performed to evaluate whether the TERT rs2736098 polymorphism is truly associated with cancer risk.…”

“…The search methods yielded 131 articles, and 5 articles were identified that met our inclusion criteria (Savage et al, 2007;Jin et al, 2009;Liu et al, 2010;Chen et al, …”