Dataset Information

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

ABSTRACT: The common sequence variants that have recently been associated with cancer risk are particular to a single cancer type or at most two. Following up on our genome-wide scan of basal cell carcinoma, we found that rs401681[C] on chromosome 5p15.33 satisfied our threshold for genome-wide significance (OR = 1.25, P = 3.7 x 10(-12)). We tested rs401681 for association with 16 additional cancer types in over 30,000 cancer cases and 45,000 controls and found association with lung cancer (OR = 1.15, P = 7.2 x 10(-8)) and urinary bladder, prostate and cervix cancer (ORs = 1.07-1.31, all P < 4 x 10(-4)). However, rs401681[C] seems to confer protection against cutaneous melanoma (OR = 0.88, P = 8.0 x 10(-4)). Notably, most of these cancer types have a strong environmental component to their risk. Investigation of the region led us to rs2736098[A], which showed stronger association with some cancer types. However, neither variant could fully account for the association of the other. rs2736098 corresponds to A305A in the telomerase reverse transcriptase (TERT) protein and rs401681 is in an intron of the CLPTM1L gene.

SUBMITTER: Rafnar T

PROVIDER: S-EPMC4525478 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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

Rafnar Thorunn T Sulem Patrick P Stacey Simon N SN Geller Frank F Gudmundsson Julius J Sigurdsson Asgeir A Jakobsdottir Margret M Helgadottir Hafdis H Thorlacius Steinunn S Aben Katja K H KK Blöndal Thorarinn T Thorgeirsson Thorgeir E TE Thorleifsson Gudmar G Kristjansson Kristleifur K Thorisdottir Kristin K Ragnarsson Rafn R Sigurgeirsson Bardur B Skuladottir Halla H Gudbjartsson Tomas T Isaksson Helgi J HJ Einarsson Gudmundur V GV Benediktsdottir Kristrun R KR Agnarsson Bjarni A BA Olafsson Karl K Salvarsdottir Anna A Bjarnason Hjordis H Asgeirsdottir Margret M Kristinsson Kari T KT Matthiasdottir Sigurborg S Sveinsdottir Steinunn G SG Polidoro Silvia S Höiom Veronica V Botella-Estrada Rafael R Hemminki Kari K Rudnai Peter P Bishop D Timothy DT Campagna Marcello M Kellen Eliane E Zeegers Maurice P MP de Verdier Petra P Ferrer Ana A Isla Dolores D Vidal Maria Jesus MJ Andres Raquel R Saez Berta B Juberias Pablo P Banzo Javier J Navarrete Sebastian S Tres Alejandro A Kan Donghui D Lindblom Annika A Gurzau Eugene E Koppova Kvetoslava K de Vegt Femmie F Schalken Jack A JA van der Heijden Henricus F M HF Smit Hans J HJ Termeer René A RA Oosterwijk Egbert E van Hooij Onno O Nagore Eduardo E Porru Stefano S Steineck Gunnar G Hansson Johan J Buntinx Frank F Catalona William J WJ Matullo Giuseppe G Vineis Paolo P Kiltie Anne E AE Mayordomo José I JI Kumar Rajiv R Kiemeney Lambertus A LA Frigge Michael L ML Jonsson Thorvaldur T Saemundsson Hafsteinn H Barkardottir Rosa B RB Jonsson Eirikur E Jonsson Steinn S Olafsson Jon H JH Gulcher Jeffrey R JR Masson Gisli G Gudbjartsson Daniel F DF Kong Augustine A Thorsteinsdottir Unnur U Stefansson Kari K

Nature genetics 20090118 2

The common sequence variants that have recently been associated with cancer risk are particular to a single cancer type or at most two. Following up on our genome-wide scan of basal cell carcinoma, we found that rs401681[C] on chromosome 5p15.33 satisfied our threshold for genome-wide significance (OR = 1.25, P = 3.7 x 10(-12)). We tested rs401681 for association with 16 additional cancer types in over 30,000 cancer cases and 45,000 controls and found association with lung cancer (OR = 1.15, P = ...[more]

PMID: 19151717

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Project description:The objective of the present study was to analyze the relationship between genetic polymorphisms of the rs2736098 locus of the telomerase reverse transcriptase (TERT) gene and the rs401681 locus of the cleft lip and palate transmembrane protein 1 (CLPTM1L) gene and the risk of developing lung cancer in males in Jinzhou. A total of 214 lung cancer patients who were admitted in Jinzhou Medical University were analyzed, and 216 healthy males were selected as controls. Venous blood from all subjects and data on relevant risk factors were collected. DNA was extracted from peripheral blood by the phenol-chloroform method. Real-time fluorescent quantitative PCR (TaqMan real-time PCR) was used for DNA amplification. The genotyping results of the genetic polymorphisms of the TERT rs2736098 and CLPTM1L rs401681 loci were detected. The risk of developing lung cancer in the population with the TERT rs2736098 locus carrying the T allele was 1.614 times that with the TERT rs2736098 locus carrying the C allele after adjustment of the age factor. The risk of developing lung cancer in the population carrying the TT mutant genotype and the CT genotype increased significantly compared with that carrying the CC wild genotype [odds ratio (OR)=1.815, 95% CI=1.132-2.957; OR=2.417, 95% CI=1.158-4.943]. Based on a comparison between the combination of the two mutant genotypes (CT+TT) and the wild homozygous genotype (CC), the mutant genotype increased the risk of developing lung cancer (OR=1.955, 95% CI=1.213-3.157). The risk of developing lung cancer in the population with the CLPTM1L rs401681 locus carrying the T allele was 1.399 times that carrying the C allele (OR=1.343, 95% CI=1.035-1.978). The population with the TERT rs2736098 locus carrying the mutant genotype (CT+TT) was associated with the number of tumors (OR=0.553, 95% CI=0.236-0.928). In conclusion, in males, the TERT rs2736098 and CLPTM1L rs401681 T alleles are the susceptibility factors for developing lung cancer. Individuals, including the smoking population, who carry both the TERT rs2736098 and CLPTM1L rs401681 T alleles are more likely to develop lung cancer.

Dataset Information

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

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

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