Faculty Collaboration Database

TP53, MDM2, NQO1, and susceptibility to cervical cancer. Cancer Epidemiol Biomarkers Prev 2010 Mar;19(3):755-61

Date

03/05/2010

Pubmed ID

20200430

Pubmed Central ID

PMC2837516

DOI

10.1158/1055-9965.EPI-09-0886

Scopus ID

2-s2.0-77949725819 (requires institutional sign-in at Scopus site)   51 Citations

Abstract

Host genetic variability modifies the risk of cervical cancer in women infected with oncogenic human papillomavirus (HPV). Studies have reported an association of the TP53 codon 72 arginine and cervical cancer, but the results are inconsistent. We examined the association of this single nucleotide polymorphism (SNP) in women with cervical cancer and cervical intraepithelial neoplasia grade 3, using a family-based association test. We further explored SNPs in two genes that regulate p53 stability: MDM2 (SNP309) and NQO1 (SNP609, SNP465). We also examined the relationship between host genotype and tumor HPV type. We genotyped 577 patients and their biological parents and/or siblings, using PCR-RFLP or Taqman assays. HPVs were typed by sequence-based methods. The transmission/disequilibrium test was used to detect disease-susceptibility alleles. The arginine peptide of TP53 codon 72 was overtransmitted in Caucasian families (P = 0.043), and the significance of this finding was enhanced in a subgroup of women infected with HPV16- and/or HPV18-related HPVs (P = 0.026). Allele C of NQO1 SNP609 was also overtransmitted in all cases (P = 0.026). We found no association between MDM2 SNP309 or NQO1 SNP465 and cervical cancer. Our results indicate that functional polymorphisms in TP53 codon 72 and NQO1 SNP609 associate with the risk of cervical cancer especially in women infected with type 16- and/or type 18-related HPVs.

Author List

Hu X, Zhang Z, Ma D, Huettner PC, Massad LS, Nguyen L, Borecki I, 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
Female
Genes, p53
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Human papillomavirus 16
Human papillomavirus 18
Humans
NAD(P)H Dehydrogenase (Quinone)
Neoplasm Staging
Papillomavirus Infections
Polymerase Chain Reaction
Polymorphism, Restriction Fragment Length
Polymorphism, Single Nucleotide
Proto-Oncogene Proteins c-mdm2
Uterine Cervical Neoplasms