Polymorphisms of a disintegrin and metalloproteinase with thrombospondin motifs 5 and Aflatoxin B1 related-hepatocellular carcinoma
Menée en Chine, cette étude évalue l'association entre 74 polymorphismes du gène ADAMTS5 et le risque de carcinome hépatocellulaire lié à l'aflatoxine B1, ainsi que la survie des patients (1 706 cas et 2 270 témoins)
Background:Altered expression of a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) is observed in hepatocellular carcinoma (HCC). The genetic polymorphisms of this gene in aflatoxin B1 (AFB1)-related HCC have not yet been elucidated. Methods:We conducted a hospital-based case-controlled study, including 1706 HCC cases and 2270 controls without any liver diseases or tumors, to assess the association between 74 polymorphisms in ADAMTS5 and AFB1-related HCC risk and prognosis. Genotype, mRNA levels, and TP53 gene mutation (TP53M) related to AFB1 exposure were tested using TaqMan-PCR or sequencing technique. ADAMTS5 protein level and micro-vessel density were analyzed by immunohistochemistry. Results:Among these 74 polymorphisms, only rs2830581 affected HCC risk. Compared with the homozygote of rs2830581 G alleles (rs2830581-GG), the genotypes of rs2830581 A alleles (rs2830581-GA or -AA) increased HCC risk (odds ratio: 1.85 and 4.40, 95% confidence interval: 1.57-2.19 and 3.43-5.64, respectively). Significant interactive effects between risk genotypes and AFB1 exposure status were also observed in the joint effects analysis. Furthermore, the rs2830581 polymorphism modified the tumor recurrence-free survival and overall survival of patients. This polymorphism not only affected pathological features of HCC such as tumor dedifferentiation and micro-vessel density, but also modified ADAMTS5 expression and the effects of transarterial chemoembolization treatment on HCC. Conclusions:These results suggest ADAMTS5 polymorphisms may be risk and prognostic biomarkers of AFB1-related HCC, and rs2830581 is a potential candidate. Impact:Our findings support the hypothesis that ADAMTS5 rs2830581 polymorphism modifies AFB1-related HCC risk and prognosis.