Association of <i>ADH1B</i> Arg47His polymorphism with the risk of cancer: a meta-analysis

Tan, Boyu; Ning, Ning

doi:10.1042/bsr20181915

Cited by 14 publications

(17 citation statements)

References 79 publications

(31 reference statements)

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“…A recent meta-analysis found no significant association between rs1229984, colorectal, hepatocellular, stomach nor pancreatic cancer supporting our findings of no association between rs1229984 and specific cancer phenotypes in this study (26). However, lung cancer was not explored in this meta-analysis due to low reporting in studies suggesting research into associations with lung cancer require larger Table IV.…”

Section: Discussionsupporting

confidence: 87%

“…Multinomial logistic regression association analysis using recessive inheritance genetic model (Arg/Arg+Arg/His: His/His). sample sizes (26). The true effect of ADH gene SNPs on alcohol metabolism is debated.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, there may be uncontrolled confounders such as diet, levels of alcohol consumption, occupational status, socioeconomic status or ethnicity that may affect both the expression of rs1229984 and overall cancer risk. Indeed, rs1229984 has shown reduced cancer risk amongst Asians and mixed ethnicity groups, but increased risk amongst Caucasians suggesting there may be ethnic differences in alcohol metabolism and cancer risk (26). Measurement bias was reduced through machine genotype identification; however, autopsy practice may have differed between pathologists leading to potential misclassification of cancer outcomes.…”

Section: Crude or A Adjusted Or B -----------------------------------mentioning

confidence: 99%

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Association between rs1229984 in ADH1B and cancer prevalence in a Japanese population

et al. 2020

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Alcohol consumption is an established risk factor for cancer, but little is known regarding the effect of genetic polymorphisms in alcohol metabolism genes on alcohol-related cancer risk in the Japanese population. Associations between the ADH1B gene (alcohol dehydrogenase 1B), single nucleotide polymorphism (SNP) rs1229984 and cancer have been extensively studied yet evidence is inconsistent. This population-based case-control study primarily aimed to clarify any association between SNP rs1229984 in both overall and specific cancer risk in a Japanese population. The functional non-synonymous SNP rs1229984 (Arg48His) was genotyped using DNA samples from 1,359 consecutive autopsy cases registered in The Japanese Single Nucleotide Polymorphisms for Geriatric Research database. Medical and pathological record data from this database were used to categorise cases and controls. Results included 1,359 participants, 816 cases and 543 controls. Multinomial logistic regression analyses showed no significant association between rs1229984 presence and overall cancer risk in both dominant and recessive genetic inheritance models [Arg/Arg+Arg/His vs. His/His: Adjusted odds ratio (OR)=0.66 (95% CI=0.39-1.13; P=0.129), Arg/Arg vs. Arg/His+His/His: OR=0.95 (95% CI=0.75-1.20; P=0.657)]. However, results showed those homozygous for rs1229984 (genotype His/His) were at significantly decreased odds of lung cancer than other genotypes [recessive model: OR=0.64 (95% CI=0.44-0.93; P=0.020]. In conclusion, there was no significant association between rs1229984 and odds of overall or specific cancers except in lung cancer where His/His genotype decreased odds. To the best of our knowledge, the association between His/His and decreased odds of lung cancer is a novel finding. These findings require further validation in larger studies.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Crude or A Adjusted Or B -----------------------------------mentioning

confidence: 99%

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Association between rs1229984 in ADH1B and cancer prevalence in a Japanese population

et al. 2020

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“…The effect on head and neck cancer appeared to be, at least, partially attributed to an increase risk of cancer of the larynx. These results correspond well to the published associations of the genetic variant, described earlier 333435 , as well as studies showing that laryngeal cancers are reversible following alcohol cessation 38 . The observed non-significant increase in the risk of cancer for those consuming alcohol in light and moderate quantities below the recommended threshold has been previously reported 28 though conflicting observational results are also available, especially for breast cancer.…”

Section: Discussionsupporting

confidence: 92%

“…The lack of association of the specific variant with stomach cancer agrees with other published data 223132 , though other alcohol associated SNPs have been reported as associated with the outcome. The rs1229984 variant though has been previously associated with aerodigestive cancers, including oral and pharynx, larynx and oesophagus cancers 333435 . Despite not identifying the reported associations, our estimated effects per unit/week were very close to what was reported earlier in a sample of 3,800 cases and 5,200 controls 33 , suggesting that more cancer cases were required to identify some of the associations present.…”

Section: Discussionmentioning

confidence: 99%

Alcohol causes an increased risk of head and neck but not breast cancer in individuals from the UK Biobank study: A Mendelian randomisation analysis

Ingold

Amin

Drenos

2019

Preprint

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Alcohol intake and the risk of various types of cancers have been previously correlated. Correlation though does not always mean that a causal relationship between the two is present. Excessive alcohol consumption is also correlated with other lifestyle factors and behaviours, such as smoking and increased adiposity, that also affect the risk of cancer and make the identification and estimation of the causal effect of alcohol on cancer difficult. Here, using individual level data for 322,193 individuals from the UK Biobank, we report the observational and causal effects of alcohol consumption on types of cancer previously suggested as correlated to alcohol. Alcohol was observationally associated with cancers of the lower digestive system, head and neck and breast cancer. No associations were observed when we considered those keeping alcohol consumption below the recommended threshold of 14 units/week. When Mendelian randomisation was used to assess the causal effect of alcohol on cancer, we found that increasing alcohol consumption, especially above the recommended level, was causal to head and neck cancers but not breast cancer. Our results where replicated using a two sample MR method and data from the much larger COGS genome wide analysis of breast cancer. We conclude that alcohol is causally related to head and neck cancers, especially cancer of larynx, but the observed association with breast cancer are likely due to confounding. The suggested threshold of 14 units/week appears suitable to manage the risk of cancer due to alcohol.

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Impacts of ADH1B rs1229984 and ALDH2 rs671 polymorphisms on risks of alcohol‐related disorder and cancer

et al. 2022

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Background ADH1B rs1229984 and ALDH2 rs671 are the specifically prevalent functional variants in the East Asians. These variants, which result in a dramatic change in enzyme activity, are highly associated with alcohol‐related disorders and cancer. Previous studies focusing on the additive and synergic effects of the variants are few and inconsistent. The aim of the research was to evaluate the associations of ADH1B rs1229984 and ALDH2 rs671 with the risks of alcohol‐related disorder and cancer. Methods This cohort study enrolled 42,665 participants from the Taiwan Precision Medicine Initiative database, including 19,522 and 20,534, ADH1B and ALDH2 carriers, respectively. The associations between the two variants and cancer risk were analyzed by univariable and multivariable logistic regression. Results Compared with the noncarriers, the ADH1B rs1229984 variant had a stronger effect on alcohol‐related disorders and was related to an increased risk of alcohol‐related cancers. The CC genotype of ADH1B rs1229984 was significantly associated with cancer of the larynx, pharynx, and nasal cavities [odds ratio (OR) = 1.56, p = 0.0009], cancer of the pancreas (OR = 1.66, p = 0.018), and cancer of the esophagus (OR = 4.10, p < 0.001). Participants who carried the rs1229984 TC/CC and rs671 GG genotypes were at higher risk of esophageal cancer (OR = 3.02, p < 0.001). The risk of esophageal cancer was increased by 381% (OR = 4.81, p < 0.001) in those carrying the rs1229984 TC/CC and rs671 GA/AA genotypes. Conclusion rs1229984 and rs671 are common and functionally important genetic variants in the Taiwanese population. Our findings provide strong evidence of additive and synergic risks of ADH1B and ALDH2 variants for alcohol‐related disorders and cancer. The results suggested that are reduction in alcohol consumption should be advised as a preventive measure for high‐risk patients carrying ADH1B rs1229984 C or the ALDH2 rs671 A allele.

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Association of ADH1B Arg47His polymorphism with the risk of cancer: a meta-analysis

Cited by 14 publications

References 79 publications

Association between rs1229984 in ADH1B and cancer prevalence in a Japanese population

Association between rs1229984 in ADH1B and cancer prevalence in a Japanese population

Alcohol causes an increased risk of head and neck but not breast cancer in individuals from the UK Biobank study: A Mendelian randomisation analysis

Impacts of ADH1B rs1229984 and ALDH2 rs671 polymorphisms on risks of alcohol‐related disorder and cancer

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