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. Copyright (c) 2010 Elsevier Inc. All rights reserved.
OBJECTIVE: Laminin-5 is required in RAS and NF-kappaB blockade induced tumorigenesis of humansquamous 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 LAMB3rs2566 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 LAMB3rs2566 may contribute to cervical cancer carcinogenesis, and further validations in diverse populations and functional characterizations are warranted. Copyright (c) 2010 Elsevier Inc. All rights reserved.