Genetic variations in EGFR and ERBB4 increase susceptibility to cervical cancer.
OBJECTIVE
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.
Department of Genetics, Washington University School of Medicine in St. Louis, MO, USA.
Duanduan
D
Ma
Raymond L
RL
Hovey
Zhengyan
Z
Zhang
Samantha
S
Fye
Phyllis C
PC
Huettner
Ingrid B
IB
Borecki
Janet S
JS
Rader
D000328:Adult; D002278:Carcinoma in Situ / Q000201:enzymology / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007438:Introns; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D066247:Receptor, ErbB-4; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000235:genetics*
C512478:EGFR protein, human; C587689:ERBB4 protein, human; D066246:ErbB Receptors; D066247:Receptor, ErbB-4
Cervical cancer; EGFR; ERBB4; Polymorphism; Transmission disequilibrium test