Chemokine RANTES promoter dimorphisms and hepatocellular carcinoma occurrence in patients with alcoholic or HCV-related cirrhosis
Menée auprès de 496 participants, cette étude française évalue l’impact de deux polymorphismes génétiques du promoteur de la chimiokine RANTES sur le risque de carcinome hépatocellulaire de patients atteints de cirrhose liée au virus de l’hépatite C ou à l’alcool
Background: This study explores the influence of two functional genetic polymorphisms in the RANTES promoter on the risk of hepatocellular carcinoma (HCC) occurrence in patients with alcoholic or HCV-related cirrhosis. Methods: RANTES C-28G and G-403A promoter dimorphisms and RANTES serum levels were assessed in 243 HCV-infected patients and 253 alcoholic patients, included at the time of diagnosis of cirrhosis and prospectively followed-up. Results: During a mean follow-up time of 76 months, 137 (27.6%) patients developed HCC and 170 (34.2%) died or were transplanted. During follow-up, patients with alcoholic cirrhosis and bearing two copies of the RANTES G-403 variant (2G-403 genotype, n = 156/253) had a higher rate of HCC occurrence compared to patients carrying at least one RANTES A-403 allele (26.3% vs. 8.2%, P = 0.0004). The RANTES 2G-403 genotype was a risk factor for HCC occurrence (HR = 3.0 [1.3-5.8]; first quartile time to HCC occurrence: 60 vs. 120 months; LogRank = 0.007) and death (HR = 1.4 [1.0-2.0]; median time to death: 55 vs. 79 months; LogRank = 0.01) in this subgroup. Carriage of the RANTES 2G-403 genotype was not associated with HCC development or death in patients with HCV-related cirrhosis. The RANTES C-28G dimorphism did not influence the occurrence of death or HCC in either cohort of patients. Conclusions: This study suggests an influence of the chemokine RANTES G-403A dimorphism on the occurrence of HCC in patients with alcoholic cirrhosis. Impact: Our findings provide clues for future studies on RANTES gene in relation to HCC susceptibility.