Genetic Factors Related to Alcohol Use

Genetic Factors Related to Alcohol Use

Critique 037.  Genes found to relate to level of alcohol consumption among Asians.

27 March 2011

Reference:  Baik I, Cho NH, Kim SH, Han B-G, Shin C.  Genome-wide association studies identify genetic loci related to alcohol consumption in Korean men.  Am J Clin Nutr 2011;93:809–816.

Accompanying Editorial:  Agrawal A, Freedman ND, Bierut LJ.  Genome-wide association studies of alcohol intake—a promising cocktail?  Am J Clin Nutr 2011;93:681–683.

In a study of 1,721 Korean male drinkers aged 40–69 y in an urban population–based cohort, and another sample of 1,113 male drinkers from an independent rural cohort, information on average daily alcohol consumption was collected and DNA samples were collected for genotyping.  In a genome-wide association (GWA) study, 12 single-nucleotide polymorphisms (SNPs) on chromosome 12q24 had genome-wide significant associations with alcohol consumption.  These polymorphisms were closely related to genes that determine levels of ALDH, low levels of which relate to flushing after even small amounts of alcohol.  Such enzymes are much more common among Asians than among westerners.  Further, associations were tested only with the weekly amount of alcohol consumed, not the pattern of drinking; hence, these findings are not direct measures of alcoholism.

The editorial by Freedman et al states “epidemiologic literature suggests that those who begin drinking at an early age may be at greater risk for a maladaptive and more genetically pronounced form of alcohol consumption, and other environmental milieus affect the risk of alcoholism.”   It will be important to investigate the interplay of genes and environmental factors when seeking the determinants of alcohol abuse.  Despite the findings of this study, our understanding of factors associated with alcoholism remains very limited.

Critique 001. Genetic effects on alcohol metabolism modify the relation of alcohol to breast cancer. 24 April 2010

Reference:  Larsen SB, Vogel U, Christensen J, Hansen RD, Wallin H, Overvad K,     Tjønneland A, Tolstrup I.    Interaction between ADH1C Arg²⁷²Gln and alcohol intake in relation to breast cancer risk suggests that ethanol is the causal factor in alcohol related breast cancer.  Cancer Letters, 2010, in press.

A study from Germany compared the association between alcohol and breast cancer risk according to genetic variations affecting levels of alcohol dehydrogenase, an enzyme that clears alcohol from the blood stream.  The authors conclude that genetic factors associated with the slow clearance of alcohol are associated with increased risk of breast cancer for drinkers; an increase in cancer risk was not seen for drinkers with genetic factors leading to fast clearance of alcohol.  Such a finding would suggest that alcohol itself is the cause of an increase in breast cancer risk among drinkers.

Unfortunately, some previous studies have shown the opposite, that an increase in breast cancer risk occurs only among women who have genes associated with fast, rather than slow, alcohol metabolism.  Overall, current scientific data indicate that breast cancer’s relation to drinking is not resolved, remaining murky and conflicted, and perhaps overemphasized. This facet of that murkiness is itself also conflicted.  As of now, it is unclear the degree to which genes affecting alcohol dehydrogenase modify the association between alcohol and the risk of breast cancer and other diseases.