Abstract 880: Polymorphisms of PLCE1 and KIF1B and risk of squamous cell carcinoma of the head and neck

Abstract

Abstract Recent genome-wide association studies (GWAS) of gastric cancer, esophageal squamous cell carcinoma and hepatocellular carcinoma have identified PLCE1 and KIF1B as novel cancer susceptibility genes. In this study, we investigated associations between risk of squamous cell carcinoma of the head and neck (SCCHN) and potentially functional variants in PLCE1 and KIF1B. Three single nucleotide polymorphisms (SNPs, rs2274223G>A, rs3203713G>A and rs11599672T>G) of PLCE1 and four SNPs (rs17401966A>G, rs1002076G>A, rs17401588A>G and rs1536262C>T) of KIF1B were genotyped by Taqman in 1,098 patients with SCCHN and 1,090 cancer-free controls, who were non-Hispanic whites matched by age (± 5 years) and sex. Although none of three SNPs of PLCE1 was alone significantly associated with overall risk of SCCHN, the combined genotypes [the number (0-6) of putative risk alleles (rs2274223G, rs3203713G and rs11599672G)] had a significant locus-dose effect on risk of SCCHN (Ptrend=0.046), particularly of non-oropharyngeal cancers (P trend=0.017), suggesting a joint effect of these SNPs on susceptibility to SCCHN. Further, the subgroup analysis showed that variant genotypes of rs2274223 and rs11599672 were independently associated with risk of non-oropharyngeal cancers, respectively. Of four SNPs of KIF1B, we found that rs1536262 variant had a significant association with the increased risk of SCCHN (additive model: adjusted OR = 1.15, 95% CI = 1.02-1.30) and the association was more evident in older subjects, females, former smokers, subjects with tumors of hypopharynx/ larynx, and subjects with poor progression tumor. Rs1536262 is located in 3’UTR region of KIF1B, a potentially functional SNP that may affect the binding of miRNA. Continuous efforts are underway in our laboratory to investigate potentially functional significance of rs1536262 in the development of SCCHN. In conclusion, our findings implicated a possible role of PLCE1 and KIF1B variants in the susceptibility to SCCHN, but larger studies are needed to validate our findings. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 880. doi:10.1158/1538-7445.AM2011-880