{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Alcohol dehydrogenase 1C (ADH1C) is a key enzyme in ethanol metabolism that catalyzes the oxidation of ethanol to acetaldehyde. Genetic polymorphisms in ADH1C—most notably the common *1 and *2 alleles—result in differences in enzymatic activity, with the *1 allele generally conferring a more rapid conversion of ethanol to acetaldehyde. This increased catalytic efficiency may lead to higher local acetaldehyde levels, which in turn can affect both the immediate physiological responses to alcohol (such as flushing) and longer‐term consequences related to alcohol exposure. Studies in diverse populations have demonstrated that variation in ADH1C is associated with differences in alcohol consumption behavior and risk for alcohol dependence (for example, see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": " In addition, epidemiologic investigations have linked ADH1C variation—particularly the fast-metabolizing ADH1C*1 allele—to an elevated risk of alcohol-associated cancers, including those of the upper aerodigestive tract (encompassing head and neck, esophageal, and hepatocellular carcinomas), as well as associations with alterations in estrogen metabolism that may impact breast cancer risk."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "16"}]}, {"type": "t", "text": " Notably, some studies have reported only nominal or null associations in certain cancer types or populations, emphasizing that the impact of ADH1C polymorphisms likely depends upon interactions with other genetic factors (such as variations in ADH1B or ALDH2) as well as environmental exposures. Collectively, the available evidence supports a dual role for ADH1C in modulating both the behavioral aspects of ethanol consumption and the biological effects of alcohol—through its influence on acetaldehyde production—in a manner that may alter susceptibility to alcohol dependence and alcohol-related cancers.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jens Treutlein, Sven Cichon, Monika Ridinger, et al. 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