Genetic variations in EGFR and ERBB4 increase susceptibility to cervical cancer |
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Authors: | Duanduan Ma Raymond L Hovey Zhengyan Zhang Samantha Fye Phyllis C Huettner Ingrid B Borecki Janet S Rader |
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Institution: | 1. Department of Genetics, Washington University School of Medicine in St. Louis, MO, USA;2. Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI, USA;3. Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, MO, USA |
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Abstract: | ObjectivesInherited 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.MethodsWe 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.ResultsBased 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.ConclusionsOur 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. |
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Keywords: | EGFR ERBB4 Cervical cancer Polymorphism Transmission disequilibrium test |
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