Polymorphisms Involved in the MiR-218-LAMB3 Pathway and Susceptibility of Cervical Cancer, a Case-control Study in Chinese Women

Objective: Laminin-5 is required in RAS and NF-kappaB blockade induced tumorigenesis of human squamous cell carcinoma and a marker of invasiveness in cervical lesions. MicroRNA-218 (miR-218) can target laminin-5 beta3 (LAMB3), but suppressed by HPV-16 E6 protein. Therefore, we hypothesized that single nucleotide polymorphisms (SNPs) in pri-miR-218 and LAMB3 may individually and/or jointly contribute to cervical cancer carcinogenesis.

Methods: We identified one SNP rs11134527 located in pri-miR-218 sequence and one SNP rs2566 in 3'UTR of LAMB3 and genotyped these two SNPs in a case-control study of 703 cervical cancer cases and 713 cancer-free controls in Chinese women.

Results: Logistic regression analyses showed that the pri-miR-218 rs11134527 variant homozygote GG was associated with a decreased risk of cervical cancer compared with the AA genotype (adjusted OR=0.72, 95% CI=0.52-0.99), while the LAMB3 rs2566 variant CT/TT genotypes were associated with a significantly increased risk of cervical cancer (adjusted OR=1.57, 95% CI=1.25-1.96), compared with the wild type CC genotype. A significant dose-response effect was observed between the number of risk alleles, rs11134527A and rs2566 T, and the risk of cervical cancer (P for trend=0.0006).

Conclusion: These findings indicate that pri-miR-218 rs11134527 and LAMB3 rs2566 may contribute to cervical cancer carcinogenesis, and further validations in diverse populations and functional characterizations are warranted.