Abstract
BackgroundPhospholipase C epsilon 1 (PLCE1) (an effector of Ras) belonging to the phospholipase family plays crucial roles in carcinogenesis and progression of several cancers, including squamous cell carcinoma of the head and neck (SCCHN). A single nucleotide polymorphism (SNP, rs2274223) in PLCE1 has been identified as a novel susceptibility locus in genome-wide association studies (GWAS) of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) that share similar risk factors with SCCHN. Therefore, we investigated the association between potentially functional SNPs in PLCE1 and susceptibility to SCCHN.MethodsWe genotyped three potentially functional SNPs (rs2274223A/G, rs3203713A/G and rs11599672T/G) of PLCE1 in 1,098 SCCHN patients and 1,090 controls matched by age and sex in a non-Hispanic white population.ResultsAlthough none of three SNPs was alone significantly associated with overall risk of SCCHN, their combined effects of risk alleles (rs2274223G, rs3203713G and rs11599672G) were found to be associated with risk of SCCHN in a locus-dose effect manner (Ptrend = 0.046), particularly for non-oropharyngeal tumors (Ptrend = 0.017); specifically, rs2274223 was associated with a significantly increased risk (AG vs. AA: adjusted OR = 1.29, 95% CI = 1.01-1.64; AG/GG vs. AA: adjusted OR = 1.30, 95% CI = 1.03-1.64), while rs11599672 was associated with a significantly decreased risk (GG vs. TT: adjusted OR = 0.54, 95% CI = 0.34-0.86; TG/GG vs. TT: adjusted OR = 0.76, 95% CI = 0.61-0.95).ConclusionsOur findings suggest that PLCE1 variants may have an effect on risk of SCCHN associated with tobacco and alcohol exposure, particularly for those tumors arising at non-oropharyngeal sites. These findings, although need to be validated by larger studies, are consistent with those in esophageal and gastric cancers.
Highlights
Phospholipase C epsilon 1 (PLCE1) belonging to the phospholipase family plays crucial roles in carcinogenesis and progression of several cancers, including squamous cell carcinoma of the head and neck (SCCHN)
We detected a significant interaction between alcohol status and rs2274223 variant genotypes (AA and AG/GG) for risk of SCCHN arising at nonoropharyngeal sites, even after the Bonferroni correction (Pint = 0.004). In this case-control study, we investigated the associations between three novel, potentially functional single nucleotide polymorphisms (SNPs) of PLCE1 and risk of SCCHN in a non-Hispanic white population
We did not find evidence of a main effect of each PLCE1 SNP on overall SCCHN risk, the joint effect of these variants appeared to contribute to risk of SCCHN in a doseresponse manner, especially for cancers arising at nonoropharyngeal sites
Summary
Phospholipase C epsilon 1 (PLCE1) (an effector of Ras) belonging to the phospholipase family plays crucial roles in carcinogenesis and progression of several cancers, including squamous cell carcinoma of the head and neck (SCCHN). A single nucleotide polymorphism (SNP, rs2274223) in PLCE1 has been identified as a novel susceptibility locus in genome-wide association studies (GWAS) of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) that share similar risk factors with SCCHN. Only one recent GWAS focused on SCCHN risk and identified five variants at 4q21, 12q24 and ADH gene cluster, significantly associated with risk of upper aerodigestive tract cancers (UATC) including SCCHN [8]. It may be a very small proportion of SNPs associated with SCCHN risk because of the strict criteria for the GWAS significance level (P = 10-7 or P = 10-8). Further exploration for the genetic variants that did not reach the GWAS significance level in the development of SCCHN is needed
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