ALDH2 polymorphism and alcohol-related cancers in Asians: a public health perspective

Abstract

The occurrence of more than 200 diseases, including cancer, can be attributed to alcohol drinking. The global cancer deaths attributed to alcohol-consumption rose from 243,000 in 1990 to 337,400 in 2010. In 2010, cancer deaths due to alcohol consumption accounted for 4.2% of all cancer deaths. Strong epidemiological evidence has established the causal role of alcohol in the development of various cancers, including esophageal cancer, head and neck cancer, liver cancer, breast cancer, and colorectal cancer. The evidence for the association between alcohol and other cancers is inconclusive. Because of the high prevalence of ALDH2*2 allele among East Asian populations, East Asians may be more susceptible to the carcinogenic effect of alcohol, with most evidence coming from studies of esophageal cancer and head and neck cancer, while data for other cancers are more limited. The high prevalence of ALDH2*2 allele in East Asian populations may have important public health implications and may be utilized to reduce the occurrence of alcohol-related cancers among East Asians, including: 1) Identification of individuals at high risk of developing alcohol-related cancers by screening for ALDH2 polymorphism; 2) Incorporation of ALDH2 polymorphism screening into behavioral intervention program for promoting alcohol abstinence or reducing alcohol consumption; 3) Using ALDH2 polymorphism as a prognostic indicator for alcohol-related cancers; 4) Targeting ALDH2 for chemoprevention; and 5) Setting guidelines for alcohol consumption among ALDH2 deficient individuals. Future studies should evaluate whether these strategies are effective for preventing the occurrence of alcohol-related cancers.

Association of low‐activity ALDH2 and alcohol consumption with risk of esophageal cancer in Chinese adults: A population‐based cohort study

“…The misclassification accounts for the weaker or nonsignificant association of EC with facial flushing than with ALDH2 genotype, as shown in our study and previous studies . When using flushing response for screening and prevention counseling, the high false‐negative rate should be particularly cautious among regular alcohol consumers, in which heterozygous carriers has risen substantially in the last few decades …”

Aldehyde dehydrogenase 2 activation ameliorates CCl4‐induced chronic liver fibrosis in mice by up‐regulating Nrf2/HO‐1 antioxidant pathway

“…ALDH2 is a key metabolic enzyme in the mitochondria, which not only metabolizes aldehyde into acetic acid, but also detoxifies toxic aldehyde substances such as 4‐HNE and MDA . Several studies have revealed the protective role of ALDH2 in alcoholic liver cirrhosis and liver cancer . Given that nearly half of the East Asian population possessed the loss‐of‐function mutation of ALDH2, the role of ALDH2 in liver fibrosis still needs further elucidation.…”

Light to moderate amount of lifetime alcohol consumption and risk of cancer in Japan

“…However, studies suggest that the ethanol (but not the other components of alcoholic beverages) matters primarily for cancer risk, regardless of the types of alcoholic beverages . In addition, we could not assess other explanatory variables such as menopausal hormone therapy (for female breast cancer), a family history of cancer, diet (eg, coffee and red meat), physical activities, and ALDH2 genotypes . In the JPHC study, alcohol‐related bladder cancer risk was observed in male “flushers” (who are supposed to have polymorphisms in ALDH2 enzyme) but not in male nonflushers .…”

“…For example, alcohol use increases circulating sex hormone levels, and this contributes to excess breast cancer risk. 13 In addition, acetaldehyde, a metabolite of ethanol classified as a group 1 carcinogen by the International Agency for Research on Cancer, stimulates Cancer March 1, 2020 cell proliferation and induces DNA damage. [6][7][8][9][10]13,14 The Japanese have a higher prevalence of polymorphisms in the aldehyde dehydrogenase 2 (ALDH2) enzyme, which makes them slower at metabolizing acetaldehyde.…”

“…13 In addition, acetaldehyde, a metabolite of ethanol classified as a group 1 carcinogen by the International Agency for Research on Cancer, stimulates Cancer March 1, 2020 cell proliferation and induces DNA damage. [6][7][8][9][10]13,14 The Japanese have a higher prevalence of polymorphisms in the aldehyde dehydrogenase 2 (ALDH2) enzyme, which makes them slower at metabolizing acetaldehyde. 9,14 Previous studies have indeed suggested an elevated cancer risk from alcohol consumption in the urinary tract and prostate in Japan, which has not been found in Western countries.…”