TP53, MDM2, NQO1, and susceptibility to cervical cancer.
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.
Hu
Xiaoxia
X
Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri, USA.
Zhang
Zhengyan
Z
Ma
Duanduan
D
Huettner
Phyllis C
PC
Massad
L Stewart
LS
Nguyen
Loan
L
Borecki
Ingrid
I
Rader
Janet S
JS
D000328:Adult; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D052162:Human papillomavirus 16; D052161:Human papillomavirus 18; D006801:Humans; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D009367:Neoplasm Staging; D030361:Papillomavirus Infections / Q000150:complications / Q000235:genetics / Q000821:virology; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000821:virology
D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2