Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 132, Issue 8, Pages 1868-1877Publisher
WILEY-BLACKWELL
DOI: 10.1002/ijc.27803
Keywords
alcohol dehydrogenase (ADH); aldehyde dehydrogenase (ALDH); alcohol; single nucleotide polymorphism (SNP); esophageal cancer
Categories
Funding
- Jiangsu Provincial Health Department [RC 2003090]
- NIH National Cancer Institute [CA09142]
- NIH [D43TW000013-21S2]
- Alper Research Center for Environmental Genomics of the UCLA Jonsson Comprehensive Cancer Center, The Graduate School VLAG, Wageningen University
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Alcohol drinking is a major risk factor for esophageal cancer (EC) and the metabolism of ethanol has been suggested to play an important role in esophageal carcinogenesis. Epidemiologic studies, including genomewide association studies (GWAS), have identified single nucleotide polymorphisms (SNPs) in alcohol dehydrogenases (ADHs) and aldehyde dehydrogenases (ALDHs) to be associated with EC. Using a population-based casecontrol study with 858 EC cases and 1,081 controls conducted in Jiangsu Province, China, we aimed to provide further information on the association of ADH1B (rs1229984), ADH1C (rs698) and ALDH2 (rs671) polymorphisms with EC in a Chinese population. Results showed that ADH1B (rs1229984) was associated with EC with odds ratios (ORs) of 1.34 [95% confidence interval (CI): 1.081.66] for G-allele carriers compared to A/A homozygotes. No heterogeneity was detected on this association across different strata of alcohol drinking and tobacco smoking. Statistical interaction between ALDH2 (rs671) and alcohol drinking on EC susceptibility in both additive and multiplicative scales was observed. Compared to G/G homozygotes, A-allele carriers were positively associated with EC among moderate/heavy drinkers (OR = 1.64, 95% CI: 1.122.40) and inversely associated with EC among never/light drinks (OR = 0.75, 95% CI: 0.541.03). In addition, statistical interaction between ALDH2 and ADH1B polymorphisms on EC susceptibility among never/light drinkers was indicated. We did not observe association of ADH1C polymorphism with EC. In conclusion, our findings indicated that ADH1B (rs1229984) was associated with EC independent of alcohol drinking and tobacco smoking status and alcohol drinking interacted with ALDH2 (rs671) on EC susceptibility in this high-risk Chinese population.
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