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Association between novel PLCE1 variants identified in published esophageal cancer genome-wide association studies and risk of squamous cell carcinoma of the head and neck.

Publication ,  Journal Article
Ma, H; Wang, L-E; Liu, Z; Sturgis, EM; Wei, Q
Published in: BMC Cancer
June 20, 2011

BACKGROUND: 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. Therefore, we investigated the association between potentially functional SNPs in PLCE1 and susceptibility to SCCHN. METHODS: We 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. RESULTS: Although 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). CONCLUSIONS: Our 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.

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Published In

BMC Cancer

DOI

EISSN

1471-2407

Publication Date

June 20, 2011

Volume

11

Start / End Page

258

Location

England

Related Subject Headings

  • United States
  • Stomach Neoplasms
  • Smoking
  • Sequence Analysis, DNA
  • Risk Factors
  • Risk
  • Polymorphism, Single Nucleotide
  • Phosphoinositide Phospholipase C
  • Organ Specificity
  • Oncology & Carcinogenesis
 

Citation

Journal cover image

Published In

BMC Cancer

DOI

EISSN

1471-2407

Publication Date

June 20, 2011

Volume

11

Start / End Page

258

Location

England

Related Subject Headings

  • United States
  • Stomach Neoplasms
  • Smoking
  • Sequence Analysis, DNA
  • Risk Factors
  • Risk
  • Polymorphism, Single Nucleotide
  • Phosphoinositide Phospholipase C
  • Organ Specificity
  • Oncology & Carcinogenesis