Faculty Collaboration Database

Genetic variations in EGFR and ERBB4 increase susceptibility to cervical cancer. Gynecol Oncol 2013 Nov;131(2):445-50

Date

08/10/2013

Pubmed ID

23927961

Pubmed Central ID

PMC3831657

DOI

10.1016/j.ygyno.2013.07.113

Scopus ID

2-s2.0-84886098361 (requires institutional sign-in at Scopus site)   10 Citations

Abstract

OBJECTIVES: Inherited genetic variability contributes to susceptibility to cervical cancer. We investigated the association of single nucleotide polymorphisms (SNPs) in the human epidermal growth factor receptor (ERBB) family with cervical cancer.

METHODS: We used the transmission disequilibrium test (TDT) to look for excessive transmission of tag single nucleotide polymorphisms (tSNPs) in ERBB family members EGFR, ERBB2, ERBB3, and ERBB4 in a large sample of women with invasive and in situ cervical cancer and their biological parents (628 trios). The study used a discovery set of trios (244) analyzed by Illumina GoldenGate in which SNPs reaching a P<.05 were re-tested by TaqMan in the combined set of 628. We also explored collaborative effects of different ERBB alleles.

RESULTS: Based on single SNP TDT tests we identified 16 significant SNPs in the discover stage and six of 14 SNPs that could be assayed by TaqMan were significantly overtransmitted in women with cervical cancer in the combined replication set. Four SNPs were located in intron 1 of EGFR and two SNPs in intron 24 of ERBB4. The EGFR variants are located near multiple enhancers, silencers, and the previously identified functional common polymorphisms in intron 1.

CONCLUSIONS: Our data provide evidence for the involvement of intron 1 EGFR variants and intron 24 ERBB4 variants in modulating risk for the development of in situ and invasive cervical cancer. These variants should be examined in additional populations and functional studies would be needed to confirm this hypothesis.

Author List

Ma D, Hovey RL, Zhang Z, Fye S, Huettner PC, Borecki IB, Rader JS

Author

Janet Sue Rader MD Chair, Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Carcinoma in Situ
Carcinoma, Squamous Cell
ErbB Receptors
Female
Genotype
Humans
Introns
Linkage Disequilibrium
Polymorphism, Single Nucleotide
Receptor, ErbB-4
Uterine Cervical Neoplasms