Association between the CDC6 G1321A polymorphism and the risk of cervical cancer.
BACKGROUND
Cell division cycle protein 6 (CDC6) plays critical roles in DNA replication and carcinogenesis. The biological significance of the CDC6 G1321A polymorphism (V441I, rs13706) on cervical carcinogenesis is still unknown. Here, we examined the potential influence of this polymorphism on cell proliferation and the individual's susceptibility to cervical cancer.


METHODS
We genotyped the CDC6 G1321A polymorphism in 87 cervical cancer cases and 110 healthy female subjects. Unconditional logistic regression analysis was used to estimate the association between the genotypes and the risk of cervical cancer. The BrdU incorporation assay was applied to analyze the effect of this polymorphism on cell proliferation.


RESULTS
Compared with the GG homozygotes, the cervical cancer risk was significantly reduced in the individuals with the heterozygous AG genotype (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.28-0.98; P = 0.042) or the homozygous AA genotype (OR, 0.29; 95% CI, 0.09-0.89; P = 0.030). Further stratified analyses showed that the decreased risk of cervical cancer was more evident among younger subjects (≤44 years old) with the AG or AA genotypes (OR, 0.44; 95% CI, 0.21-0.92; P = 0.029 and OR, 0.12; 95% CI, 0.03-0.61; P = 0.010, respectively). The BrdU incorporation assay showed that 293T cells transfected with CDC6-441I (1321A) had a lower proliferation rate in comparison with those transfected with CDC6-441V (1321G), although the difference did not reach statistical significance at the 0.05 level.


CONCLUSIONS
The CDC6 G1321A polymorphism may contribute to the risk of cervical cancer. Further studies with more subjects and in diverse ethnic populations are necessary to confirm the general validity of our findings.
Xiong
Xing-Dong
XD
Department of Biochemistry and Molecular Biology, Guangdong Medical College, Dongguan, China.
Zeng
Li-Qin
LQ
Xiong
Qing-Yuan
QY
Lu
Sheng-Xiang
SX
Zhang
Zhi-Zhen
ZZ
Luo
Xi-Ping
XP
Liu
Xin-Guang
XG
D000328:Adult; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D049109:Cell Proliferation; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000235:genetics
C103706:CDC6 protein, human; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins