Alcohol metabolism genes and risks of site-specific cancers in Chinese adults: an 11-year prospective study
Two genetic variants that alter alcohol metabolism, ALDH2-rs671 and ADH1B-rs1229984, can modify oesophageal cancer risk associated with alcohol consumption in East Asians, but their associations with other cancers remain uncertain. ALDH2-rs671 G>A and ADH1B-rs1229984 G>A were genotyped in 150,...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Wiley
2022
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| _version_ | 1797050725475287040 |
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| author | Im, P Yang, L Kartsonaki, C Chen, Y Du, H Lin, K Kerosi, R Hacker, A Walters, R Chen, Z Millwood, I |
| author_facet | Im, P Yang, L Kartsonaki, C Chen, Y Du, H Lin, K Kerosi, R Hacker, A Walters, R Chen, Z Millwood, I |
| author_sort | Im, P |
| collection | OXFORD |
| description | Two genetic variants that alter alcohol metabolism, ALDH2-rs671 and ADH1B-rs1229984, can modify oesophageal cancer risk associated with alcohol consumption in East Asians, but their associations with other cancers remain uncertain. ALDH2-rs671 G>A and ADH1B-rs1229984 G>A were genotyped in 150,722 adults, enrolled from ten areas in China during 2004-2008. After 11 years’ follow-up, 9339 individuals developed cancer. Cox regression was used to estimate hazard ratios (HRs) for site-specific cancers associated with these genotypes, and their potential interactions with alcohol consumption. Overall, the A-allele frequency was 0.21 for ALDH2-rs671 and 0.69 for ADH1B-rs1229984, with A-alleles strongly associated with lower alcohol consumption. Among men, ALDH2- rs671 AA genotype was associated with HR of 0.69 (95% CI: 0.53-0.90) for IARC alcohol related cancers (n=1900), compared with GG genotype. For ADH1B-rs1229984, the HRs of AG and AA versus GG genotype were 0.80 (0.69-0.93) and 0.75 (0.64-0.87) for IARC alcohol-related cancers, 0.61 (0.39-0.96) and 0.61 (0.39-0.94) for head and neck cancer (n=196), and 0.68 (0.53-0.88) and 0.60 (0.46-0.78) for oesophageal cancer (n=546). There were no significant associations of these genotypes with risks of liver (n=651), colorectal (n=556), stomach (n=725) or lung (n=1135) cancers. Among male drinkers, the risks associated with higher alcohol consumption were greater among ALDH2-rs671 AG than GG carriers for head and neck, oesophageal, and lung cancers (p-interaction<0.02). Among women, only 2% drank alcohol regularly, with no comparable associations observed between genotype and cancer. These findings support the causal effects of alcohol consumption on upper aero-digestive tract cancers, with ALDH2-rs671 AG genotype further exacerbating the risks. |
| first_indexed | 2024-03-06T18:09:26Z |
| format | Journal article |
| id | oxford-uuid:027f7b2e-5d4e-4b28-a071-9d2e55974650 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:09:26Z |
| publishDate | 2022 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:027f7b2e-5d4e-4b28-a071-9d2e559746502022-03-26T08:41:11ZAlcohol metabolism genes and risks of site-specific cancers in Chinese adults: an 11-year prospective studyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:027f7b2e-5d4e-4b28-a071-9d2e55974650EnglishSymplectic ElementsWiley2022Im, PYang, LKartsonaki, CChen, YDu, HLin, KKerosi, RHacker, AWalters, RChen, ZMillwood, ITwo genetic variants that alter alcohol metabolism, ALDH2-rs671 and ADH1B-rs1229984, can modify oesophageal cancer risk associated with alcohol consumption in East Asians, but their associations with other cancers remain uncertain. ALDH2-rs671 G>A and ADH1B-rs1229984 G>A were genotyped in 150,722 adults, enrolled from ten areas in China during 2004-2008. After 11 years’ follow-up, 9339 individuals developed cancer. Cox regression was used to estimate hazard ratios (HRs) for site-specific cancers associated with these genotypes, and their potential interactions with alcohol consumption. Overall, the A-allele frequency was 0.21 for ALDH2-rs671 and 0.69 for ADH1B-rs1229984, with A-alleles strongly associated with lower alcohol consumption. Among men, ALDH2- rs671 AA genotype was associated with HR of 0.69 (95% CI: 0.53-0.90) for IARC alcohol related cancers (n=1900), compared with GG genotype. For ADH1B-rs1229984, the HRs of AG and AA versus GG genotype were 0.80 (0.69-0.93) and 0.75 (0.64-0.87) for IARC alcohol-related cancers, 0.61 (0.39-0.96) and 0.61 (0.39-0.94) for head and neck cancer (n=196), and 0.68 (0.53-0.88) and 0.60 (0.46-0.78) for oesophageal cancer (n=546). There were no significant associations of these genotypes with risks of liver (n=651), colorectal (n=556), stomach (n=725) or lung (n=1135) cancers. Among male drinkers, the risks associated with higher alcohol consumption were greater among ALDH2-rs671 AG than GG carriers for head and neck, oesophageal, and lung cancers (p-interaction<0.02). Among women, only 2% drank alcohol regularly, with no comparable associations observed between genotype and cancer. These findings support the causal effects of alcohol consumption on upper aero-digestive tract cancers, with ALDH2-rs671 AG genotype further exacerbating the risks. |
| spellingShingle | Im, P Yang, L Kartsonaki, C Chen, Y Du, H Lin, K Kerosi, R Hacker, A Walters, R Chen, Z Millwood, I Alcohol metabolism genes and risks of site-specific cancers in Chinese adults: an 11-year prospective study |
| title | Alcohol metabolism genes and risks of site-specific cancers in Chinese adults: an 11-year prospective study |
| title_full | Alcohol metabolism genes and risks of site-specific cancers in Chinese adults: an 11-year prospective study |
| title_fullStr | Alcohol metabolism genes and risks of site-specific cancers in Chinese adults: an 11-year prospective study |
| title_full_unstemmed | Alcohol metabolism genes and risks of site-specific cancers in Chinese adults: an 11-year prospective study |
| title_short | Alcohol metabolism genes and risks of site-specific cancers in Chinese adults: an 11-year prospective study |
| title_sort | alcohol metabolism genes and risks of site specific cancers in chinese adults an 11 year prospective study |
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