Combined effects of E2F1 and E2F2 polymorphisms on risk and early onset of squamous cell carcinoma of the head and neck.

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.