Association between Let-7 microRNA-Binding-Site polymorphism in the KRAS 3’UTR and endometriosis: A replication study and Meta-Analysis

Background: Endometriosis is inherited as a complex genetic trait, and the single nucleotide polymorphism (SNP) rs61764370 within the KRAS gene on chromosome subband 12p12.1 has been proposed as a potential candidate gene. By disrupting a binding site for microinterference RNA (miRNA) let-7, the rs61764370 SNP variation site may increase activation of KRAS and favor disease development. Conflicting evidence, however, has emerged on the association between the rs61764370 SNP and endometriosis. Due to the potential implications of this issue for the diagnosis and treatment of endometriosis, we sought to replicate the sequencing of the KRAS rs61764370 SNP in a population of cases and controls and to perform a meta-analysis encompassing all currently available studies as well as our novel replication. Methods: We sought to replicate for the first time the sequencing of KRAS rs61764370 SNP in a highly selected population of 86 cases of women with laparoscopically proven endometriosis and 72 healthy controls, and to perform a meta-analysis encompassing currently available studies and including affected subjects (n = 2, 225) and controls (n = 1, 923). Results: The rs61764370 minor allele was observed in 12 of 86 women with endometriosis (14.0%) and in 15 of 72 controls (20.8%) (odds ratio [OR] = 0.76, 95% confidence interval [95% CI], 0.36-1.60, p = 0.48). The metaanalysis failed to identify any significant association (OR = 1.03, 95% CI, 0.89-1.20, p = 0.67, phet = 0.46). Conclusions: KRAS variation site rs61764370 is unlikely related to disease development, and other loci with potential implications for diagnosis or treatment for endometriosis should be identified.