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Genetic variability in EGFR, Src and HER2 and risk of colorectal adenoma and cancer

Authors :
Elizabeth M, Poole
Karen, Curtin
Li, Hsu
Richard J, Kulmacz
David J, Duggan
Karen W, Makar
Liren, Xiao
Christopher S, Carlson
Martha L, Slattery
Bette J, Caan
John D, Potter
Cornelia M, Ulrich
Source :
International journal of molecular epidemiology and genetics. 2(4)
Publication Year :
2011

Abstract

The EGFR signaling pathway is involved in carcinogenesis at multiple sites, particularly colorectal cancer, and is a target of colorectal cancer chemotherapy. EGFR signaling is linked to pro-carcinogenic mechanisms, including cell proliferation, survival, angiogenesis, and more recently prostaglandin synthesis. Genetic variability in this pathway has not yet been studied in relation to colorectal carcinogenesis. In three case-control studies of colorectal adenoma (n=485 cases/578 controls), colon cancer (n=1424 cases/1780 controls) and rectal cancer (n=583 cases/775 controls), we investigated associations between candidate SNPs, tagSNPs and haplotypes in EGFR signaling (EGFR, Src, and HER2) and risk. We also examined associations with tumor subtypes: TP53 and KRAS2 mutations, CpG island methylator phenotype, and microsatellite instability. All three studies were genotyped using an identical Illumina GoldenGate assay, allowing thorough investigation of genetic variability across stages and locations of colorectal neoplasia. The EGFR tagSNP 142572T>C (rs3752651) CC genotype was associated with a suggested increased risk for both colon (OR: 1.40; 95% CI: 1.00-1.96; p-trend=0.04) and rectal cancer (OR: 1.39; 95% CI: 0.81-2.41; p-trend=0.65). In tumor subtype analyses, the association was limited to TP53-mutated colon tumors. Using the Chatterjee 1 df Tukey test to assess gene-gene interactions, we observed a statistically significant (p

Subjects

Subjects :
Original Article

Details

ISSN :
19481756
Volume :
2
Issue :
4
Database :
OpenAIRE
Journal :
International journal of molecular epidemiology and genetics
Accession number :
edsair.pmid..........93695401413323fdbefcd48e8e081980