Genetic variation in <i>TERT</i> modifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: results from a genome-wide case-control study.

In the GWAS undertaken by Trépo et al 14 rs2242652:A in TERT was associated with a reduced risk of HCC, but the OR was weaker than in this study and did not reach statistical significance (p=0.179; OR=0.89 (95% CI 0.75 to 1.06)).

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Allelic and genotypic associations for TERT were highly significant, in the univariate analyses, for the comparisons HCC vs ArC (P allelic =2.81×10 −11 , P genotypic 2.32×10 −10 ) and HCC versus alcohol misuse but not for ArC vs alcohol misuse using combined genotype counts from the stage 1 and 2 data sets ( online supplemental table 8 ; figure 2 ).

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Previously reported associations of HCC in the context of ArC with variants of HSD17B13 rs72613567:TA (p=8.95×10 −3 ; OR=0.81 (95% CI 0.69 to 0.95) and APOE rs429358:C (p=5.44×10 −3 ; OR=0.74 (95% CI 0.60 to 0.91) were nominally significant in this study, but did not achieve genome-wide significance in the discovery cohort ( online supplemental tables 5 and 7 ).

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