title: Genetic variations in TERT-CLPTM1L genes and risk of squamous cell carcinoma of the head and neck.
abstract: Single-nucleotide polymorphisms (SNPs) of TERT-rs2736098 (C > T) and CLPTM1L-rs401681(C > T) at the 5p15.33 locus are significantly associated with cancer risk as reported in genome-wide association studies (GWAS), but there are no reported studies for squamous cell carcinoma of the head and neck (SCCHN). In a case-control study of 1079 SCCHN cases and 1115 cancer-free controls of non-Hispanic whites who were frequency matched by age and sex, we genotyped for these two SNPs and assessed their associations with SCCHN risk. Compared with the CC genotypes of each polymorphism, the associations of a slightly reduced risk of SCCHN with the variant genotypes of CT + TT of both polymorphisms were approaching statistical significance [Odds ratio (OR) = 0.90, 95% confidence interval (CI) = 0.76-1.08 for TERT-rs2736098 and OR = 0.86, 95% CI = 0.71-1.04 for CLPTM1L-rs401681, respectively]. When the two SNPs were combined, the variant genotypes of the two SNPs were significantly associated a moderately reduced risk of SCCHN (OR = 0.82, 95% CI = 0.67-0.99), and the number of variant genotypes was associated with a significantly reduced risk in a dose-response manner (P = 0.028). Furthermore, the reduced risk was more pronounced in ever smokers, ever drinkers and patients with oropharyngeal cancer. Our results suggested that these two SNPs at the 5p15.33 locus may be associated with a reduced risk of SCCHN, particularly for their combined effect. Although we added additional evidence for the association of the two SNPs with cancer risk as reported in GWAS, additional studies are needed to replicate our findings.
authors.affiliation: Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Guojun
authors.initials: G
authors.lastname: Li
authors.forename: Sheng
authors.initials: S
authors.lastname: Wei
authors.forename: Jiangong
authors.initials: J
authors.lastname: Niu
authors.forename: Li-E
authors.initials: LE
authors.lastname: Wang
authors.forename: Erich M
authors.initials: EM
authors.lastname: Sturgis
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D012907:Smoking; D019098:Telomerase / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C422445:CLPTM1L protein, human; D004273:DNA, Neoplasm; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C509186:TERT protein, human; D019098:Telomerase
references.citation: Clin Cancer Res. 2002 Sep;8(9):2883-9
references.pmid: 12231532
references.citation: Clin Cancer Res. 2000 Jul;6(7):2696-701
references.pmid: 10914712
references.citation: Carcinogenesis. 2009 Aug;30(8):1368-71
references.pmid: 19465454
references.citation: Clin Cancer Res. 2004 Aug 1;10(15):4983-90
references.pmid: 15297398
references.citation: Clin Cancer Res. 2001 Oct;7(10):3079-86
references.pmid: 11595698
references.citation: Gene. 1999 May 17;232(1):97-106
references.pmid: 10333526
references.citation: Crit Rev Oncol Hematol. 2006 Jul;59(1):1-14
references.pmid: 16600619
references.citation: Oncol Rep. 2009 Mar;21(3):649-63
references.pmid: 19212623
references.citation: Hum Mol Genet. 1999 Jan;8(1):137-42
references.pmid: 9887342
references.citation: Br J Cancer. 2007 Sep 17;97(6):832-6
references.pmid: 17848914
references.citation: Front Biosci. 2008 Jan 01;13:2075-90
references.pmid: 17981693
references.citation: J Natl Cancer Inst. 1997 Dec 17;89(24):1874-81
references.pmid: 9414175
references.citation: Cancer Res. 1995 Aug 1;55(15):3258-62
references.pmid: 7614459
references.citation: Oncol Rep. 2005 Sep;14(3):601-7
references.pmid: 16077962
references.citation: Int J Cancer. 2000 Dec 15;88(6):895-901
references.pmid: 11093811
references.citation: Cancer Epidemiol Biomarkers Prev. 2009 Oct;18(10):2773-81
references.pmid: 19773453
references.citation: Biochem Biophys Res Commun. 2001 Feb 2;280(4):1148-54
references.pmid: 11162647
references.citation: Nat Genet. 2008 Dec;40(12):1404-6
references.pmid: 18978790
references.citation: Cancer. 2008 Nov 15;113(10 Suppl):2901-9
references.pmid: 18980273
references.citation: Nat Genet. 1997 Dec;17(4):498-502
references.pmid: 9398860
references.citation: CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96
references.pmid: 18287387
references.citation: Nat Genet. 2009 Aug;41(8):909-14
references.pmid: 19578363
references.citation: J Biol Chem. 2004 Dec 31;279(53):55401-10
references.pmid: 15516693
references.citation: Cancer. 2007 Oct 1;110(7):1429-35
references.pmid: 17724670
references.citation: Cancer Lett. 2008 Sep 8;268(1):158-65
references.pmid: 18455294
references.citation: Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11306-11
references.pmid: 16847266
references.citation: Nat Genet. 2009 Feb;41(2):221-7
references.pmid: 19151717
references.citation: Nat Genet. 2008 Dec;40(12):1407-9
references.pmid: 18978787
references.citation: Hum Pathol. 2000 Oct;31(10):1304-12
references.pmid: 11070123
references.citation: Int J Cancer. 2001 Oct 15;94(2):153-6
references.pmid: 11668491
references.citation: Neoplasia. 2000 May-Jun;2(3):197-201
references.pmid: 10935505