Polymorphisms in HPV E6/E7 protein interacted genes and risk of cervical cancer in Chinese women: a case-control analysis.
OBJECTIVE
Accumulating studies indicate that HPV E6/E7 oncoproteins interacting genes, TP53, BRCA1 and BARD1, play a critical role in cervical carcinogenesis. We hypothesized that potentially functional polymorphisms in TP53, BRCA1 and BRAD1 may individually and/or jointly contribute to cervical cancer risk.


METHODS
We genotyped 4 single nucleotide polymorphisms (SNPs) with amino acid changes, TP53 Pro72Arg (rs1042522), BRCA1 Pro871Leu (rs799917), BARD1 Pro24Ser (rs1048108) and Arg378Ser (rs2229571), in a case-control study of 404 cervical cancer cases and 404 cancer-free controls in Chinese women.


RESULTS
Logistic regression analysis showed that the BRCA1 variant rs799917 TT genotype was associated with a significantly decreased risk of cervical cancer in a recessive genetic model (adjusted OR=0.62, 95% CI=0.40-0.95), compared with the genotypes CT/CC. However, no significant associations with cervical cancer were observed for other 3 SNPs (adjusted OR=1.01, 95% CI=0.68-1.50 for rs1048108 TT vs CT/CC; adjusted OR=1.04, 95% CI=0.67-1.64 for rs2229571 CC vs GG/GC; adjusted OR=0.84, 95% CI=0.59-1.20 for rs1042522 CC vs GG/GC).


CONCLUSIONS
These findings indicate that BRCA1 rs799917 polymorphism may contribute to the risk of cervical cancer in this Chinese population, and further validation in other populations are warranted.
Zhou
Xiaoyi
X
Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.
Han
Suping
S
Wang
Sumin
S
Chen
Xiaojun
X
Dong
Jing
J
Shi
Xiaoyan
X
Xia
Yankai
Y
Wang
Xinru
X
Hu
Zhibin
Z
Shen
Hongbing
H
D019313:BRCA1 Protein / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D002681:China; D005260:Female; D019398:Genes, BRCA1; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism; D030361:Papillomavirus Infections / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D020641:Polymorphism, Single Nucleotide; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000821:virology*
D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D009856:Oncogene Proteins, Viral; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases