Global DNA methylation levels in white blood cells as a biomarker for hepatocellular carcinoma risk: a nested case-control study
Menée sur 305 cas de carcinome hépatocellulaire et 1 254 témoins, cette étude évalue l'association entre des marqueurs d'une hypométhylation globale et la susceptibilité à cette forme de cancer
Global DNA hypomethylation is associated with genomic instability and human cancer and blood DNAs collected at the time of cancer diagnosis have been used to examine the relationship between global methylation and cancer risk. To test the hypothesis that global hypomethylation is associated with increased risk of hepatocellular carcinoma (HCC), we conducted a prospective case-control study nested within a community-based cohort with 16 years of follow up. We measured methylation levels in Sat2 by MethyLight, and LINE-1 by pyrosequencing using baseline white blood cell (WBC) DNA from 305 HCC cases and 1254 matched controls. We found that Sat2 hypomethylation was associated with HCC risk (OR per 1 unit decrease in natural log Sat2 methylation=1.77, 95% CI=1.06-2.95). The association was significant among individuals diagnosed with HCC before age of 62 (OR per 1 unit decrease in natural log Sat2 methylation=2.47, 95%CI=1.06-5.73) but not after (OR 1.67, 95%CI=0.84-3.32). We did not observe an association of LINE-1 with HCC overall, or by age at diagnosis. Among carriers of HBsAg, with each 1 unit decrease in natural log Sat2 methylation level, the OR for HCC increased by 2.19 (95% CI=1.00-4.89). LINE-1 hypomethylation was associated with about a 2-fold increased risk of HCC, with ORs (95%CI) of 2.39 (1.06-5.39), 2.09 (0.91-4.77), and 2.28 (0.95-5.51, Ptrend=0.14) for HBsAg carriers in the 3rd, 2nd, and lowest quartile of LINE-1 methylation, respectively, compared with carriers in the 4th. These results suggest that global hypomethylation may be a useful biomarker of HCC susceptibility.
Carcinogenesis , résumé, 2012