The interaction between RAGE gene polymorphisms and HPV infection in determining the susceptibility of cervical cancer in a Chinese population.

Objective: To explore the possible association between the receptor for advanced glycation end products (RAGE) gene polymorphisms and the risk of cervical cancer.

Methods: We enrolled 488 patients with cervical squamous cell carcinoma and 715 age-matched female healthy subjects as controls. Human Papillomavirus (HPV) infection and four RAGE gene polymorphisms (-429T>C, -374T>A, 1704G>T, and 82G>S) in all subjects were determined.

Results: The genotype distributions and allele frequencies of -429T>C, 1704 T>G and -374T>A were not significantly different between cervical cancer patients and controls (all P> 0.05). For 82G>S polymorphisms, the genotype distributions and allele frequencies were significantly different between the two groups. The cervical cancer patients had markedly higher percentage of 82SS carriage than controls. The logistic regression analysis showed that the 82SS genotype was associated with significantly elevated risk for cervical cancer, adjusted odds ratio (OR) was 1.98, (P< 0.001). In addition, the 82SS carriers had significantly lower serum soluble RAGE (sRAGE) levels than 82GS and 82GG. The polymorphisms of -429T>C, -374T>A and 1704T>G did not affect the cervical cancer risk and the serum sRAGE levels. When all the cancer patients were stratified by HPV infection status, the 82GS and 82SS genotype carriers in the HPV infection subgroup had increased risk for cervical cancer versus 82GG (OR=1.68 and 1.74, respectively, both P<0.05). This trend was not observed in the subgroup with no detectable HPV DNA.

Conclusions: Our results suggest that the RAGE 82G>S polymorphisms, interacting with HPV infection, are implicated in the occurrence of cervical cancer.