title: Combined effects of E2F1 and E2F2 polymorphisms on risk and early onset of squamous cell carcinoma of the head and neck.
abstract: Deregulated expression of most members of the E2F family has been detected in many human cancers. We examined the association of common single nucleotide polymorphisms (SNPs) of E2F transcription factors 1 and 2 (E2F1 and E2F2) with risk of squamous cell carcinoma of the head and neck (SCCHN) in 1,096 SCCHN patients and 1,090 cancer-free controls. We genotyped 10 selected SNPs in E2F1 and E2F2, including those at the near 5'-untranslated region (UTR), microRNA (miRNA)-binding sites at the near 3'-UTR and tagSNPs according to bioinformatics analysis. Although none of the selected SNPs alone was significantly associated with risk of SCCHN, there was a statistically significantly increased risk of SCCHN associated with the combined risk genotypes (i.e., rs3213182 AA, rs3213183 GG, rs3213180 GG, rs321318121 GG, rs2742976 GT+TT, rs6667575 GA+AA, rs3218203 CC, rs3218148 AA, rs3218211 CC, and rs3218123 GT+TT). Compared with those with 0-4 risk genotypes, an increased risk was observed for those who carried 5-8 risk genotypes (adjusted OR = 1.04; 95% CI = 0.86-1.26) and 9-10 risk genotypes (adjusted OR = 1.62; 95% CI = 1.14-2.30) in a dose-response manner (P = 0.045). Furthermore, the joint effect was more pronounced among patients with oropharyngeal cancer, younger adults (≤57 yr old), men, non-smokers, non-drinkers, and individuals with family history of cancer in first-degree relatives. Additionally, we also observed that those with 5-10 risk genotypes had an earlier SCCHN onset than those with 0-4 risk genotypes, particularly for non-smokers and/or non-drinkers. We concluded that E2F1 and E2F2 genetic variants may jointly play important roles in head and neck carcinogenesis.
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Meixia
authors.initials: M
authors.lastname: Lu
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Hongping
authors.initials: H
authors.lastname: Yu
authors.forename: Li-E
authors.initials: LE
authors.lastname: Wang
authors.forename: Guojun
authors.initials: G
authors.lastname: Li
authors.forename: Erich M
authors.initials: EM
authors.lastname: Sturgis
authors.forename: David G
authors.initials: DG
authors.lastname: Johnson
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
mesh_terms: D017668:Age of Onset; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D050687:E2F1 Transcription Factor / Q000235:genetics*; D050703:E2F2 Transcription Factor / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006258:Head and Neck Neoplasms / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011897:Random Allocation; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D050703:E2F2 Transcription Factor; C493761:E2F2 protein, human