Genetic variants at the TERT- CLPTM1L locus associate with many cancer types

Cancer is caused by a complex interplay between genetic and environmental factors. Highly penetrant mutations explain only a small fraction of cancer cases and the majority of genetic cancer risk is thought to be due to the contribution of many common sequence variants of low penetrance. In the past few years (GWA) studies have identified multiple single-nucleotide polymorphisms (SNPs) on chromosome 5, to breast, prostate, colorectal, and bladder cancer susceptibility.Rafnar et al. have discovered sequence variants in the region of the TERT and CLPTM1L genes that associate with risk of many types of cancer, and assessed the association of rs401681(C)) and rs2736098(A) with the major histological types of cancers.Rs401681 resides in an LD block that contains the CLPTM1L (cisplatin resistance related protein CRR9p) gene and the 5′ end of the TERT (human telomerase reverse transcriptase) gene. CLPTM1L is a predicted transmembrane protein that is expressed in a range of normal and malignant tissues including skin, lung, breast, ovary and cervix.Rs2736098 corresponds to A305A in the second exon of the TERT gene while rs401681 is in an intron of the CLPTM1L gene.In this study, We will test the joint effect of rs401681(C) and rs2736098(A) to find association with 5 cancer types in cancer cases ( lung, breast , prostate, colorectal and bladder ) and controls in Iranian population.

Keywords:

Cancer , SNP , CLPTM1L , TERT