For an oncologist, cancer is about focusing on the fight and not the fright; however,
for the patient and patient's family, it is frightening most of the times! There are
many risk factors associated with cancer, including modifiable and nonmodifiable.
Chronic alcohol abuse is one of the modifiable risk factors, inundated with health
problems including cancer. The International Agency for Research on Cancer monographs
classify alcohol as a Group 1 carcinogenic agent which means that alcohol is carcinogenic
to humans.[1] The evidence is primarily furnished by the epidemiological studies including case–control
and cohort studies which report the estimate of effect (relative risk). There is a
paucity of randomized controlled trials assessing both the carcinogenicity and causal
association of alcohol and cancers. The Continuous Update Project World Cancer Research
Fund/American Institute for Cancer Research reinforces that consumption of alcohol
is associated with the increased risk of cancer and also provides causal association.[2],[3] There is an increased incidence for cancers of 7 subsites secondary to alcohol consumption.
These are lip and oral cavity, oropharynx and hypopharynx, esophagus, colorectal,
liver, larynx, and breast.[4] The benefit of moderate drinking of alcohol is controversial with upsurgence of
recent data demonstrating the contrary.[5],[6]
Tobacco and alcohol are both preventable causes of cancers. The effect of simultaneous
consumption of the two is not additive but synergistic. While the efforts are being
made to curb the tobacco consumption at various levels, the measures are relatively
less proactive when it comes to alcohol. There can be multiple reasons to it including
lesser alcohol consumption in South East Asia compared to Western world, industry-driven
motives, and, to an extent, lack of awareness.
Carcinogenesis
The carcinogenesis of alcohol is through multiple metabolic pathways which are not
completely understood.[4],[7] Alcohol dehydrogenase is the enzyme that converts ethanol to acetaldehyde. Acetaldehyde
with the help of enzyme aldehyde dehydrogenase is further metabolized to acetate.
The main carcinogenic potential of alcohol is due to the metabolite acetaldehyde which
causes DNA damage. Ethanol interferes with the metabolism of estrogen. The levels
of this hormone are increased by alcohol consumption. Estrogen causes excessive cellular
proliferation leading to breast cancer. There are various other mechanisms involved
in the carcinogenesis of alcohol; one of them is by producing reactive oxygen species
along the metabolic pathway. This oxidative stress leads to lipid peroxidation which
causes the production electrophilic compounds resulting in the formation of exocyclic
DNA adducts. Consumption of alcohol and tobacco has synergistic effect which can be
explained by the fact that the alcohol acts as a solvent and facilitates absorption
of carcinogens through the mucosa of the upper aerodigestive tract.
Genetic factors are also thought to play a role in the carcinogenesis of alcohol through
polymorphisms of genes encoding enzymes and proteins involved in alcohol metabolism,
folate and methionine metabolic pathways, and DNA repair.[8] Mendelian randomization studies confirmed the above finding. The variant of aldehyde
dehydrogenase ALDH2 * 2 is prevalent in the Asian population. The individual homozygous
or heterozygous for this allele is unable to oxidize aldehyde or do it insufficiently
leading to build up of acetaldehyde and has higher chances of developing colorectal
and aerodigestive tract cancers. Methylenetetrahydrofolate reductase is the enzyme
important for DNA synthesis and methylation. This enzyme converts 5,10-methylenetetrahydrofolate
to 5-methylenetetrahydrofolate. The variant of this enzyme reduces its activity and
its role has been noted with colon cancer.
Consumption and Disease Burden
Consumption and Disease Burden
The problem of alcohol consumption is more in the West compared to Indian subcontinent.
Age-standardized prevalence of current drinking (patients consuming alcohol within
the last 12 months) in Indian subcontinent for females is between 0%–19.9% compared
to 40%–79.9% in the Western world and for males is 0%–39.9% compared to 40%–100% in
the West. Age-standardized average standard drinks daily (defined as 10 g of pure
ethanol per se rving) among current drinkers in Indian subcontinent is reported as
1.01–2 for males and <1.0 for females.[5]
Systematic analysis performed by global burden of Diseases, Injuries, and Risk Factors
Study (GBD) 2016 alcohol collaborators generated an estimate of alcohol use and alcohol
attributable deaths and disability-adjusted life years (DALYs) for 195 countries and
territories spanning over two and a half decade. The results of the study reported
that globally alcohol was the seventh leading risk factor for both deaths and DALYs
in 2016. In 2016, there were 2.8 million alcohol-attributable deaths which corresponded
to 2.2% of total age standardized deaths among females and 6.8% in males globally.
It was the leading risk factor for death globally for the population aged 15–49 years,
with alcohol-attributable death being 3.8% and 12.2% among female and male, respectively.
Among the population aged 50 years or above, alcohol-induced cancer accounted for
27.1% and 18.9% of total alcohol-attributable deaths among females and males, respectively.
Globally, in 2016, 1.6% of total DALYs were lost due to alcohol in females and 6.0%
among males in terms of overall disease burden. Alcohol use led to 8.9% of attributable
DALYs lost for males and 2.3% for females among population aged 15–49 years.[5]
Zero Level of Alcohol Consumption Is Safe to Minimize the Health Risk
Zero Level of Alcohol Consumption Is Safe to Minimize the Health Risk
The study by GBD 2016 alcohol collaborators also showed that overall risk to health
loss was minimized at consumption level of zero standard drinks daily. For alcohol-attributable
disease outcomes including cancers, the risk rose monotonically on increasing alcohol
consumption. For ischemic heart disease, the minimum relative risk was 0.86 for men
and 0.82 for women with the consumption of <1 standard drink daily for both. The relative
risk was similar across all ages. However, the protective effects of alcohol on ischemic
heart disease and diabetes were offset by the risk associated with cancers which increased
with the alcohol consumption.[5]
In 2016, alcohol caused 4.2% of all cancer deaths with the estimated number of 376,200
cancer deaths with an age standardized rate of 4.8 deaths per 100,000 people. Major
proportion of these deaths were constituted by colorectal, liver, and esophagus in
order of decreasing numbers. Alcohol consumption caused 10.3 million DALYs lost due
to cancer in 2016 corresponding to 4.2% of all cancer DALYs lost. There is geographic
variation for alcohol-attributable cancer burden, being lowest in North Africa and
Middle East and highest in Europe. Age-standardized cancer deaths attributable to
alcohol consumption in 2016 is between 0.8 and 3.3/100,000 people representing up
to 3.3% of cancer deaths and 24–103 age standardized cancer DALYs attributable to
alcohol per 1,000,000 people attributable to alcohol in Indian subcontinent.[2],[9]
Measures to Decrease Alcohol Consumption
Measures to Decrease Alcohol Consumption
Alcohol is a preventable cause of cancer and hence efforts should be directed to decrease
its consumption. Paradoxically, everything can be preserved in alcohol, but for health,
wealth and happiness. A study by Alattas et al. looked at alcohol policies and alcohol-attributable cancer mortality. They reported
that more restrictive alcohol policies were associated with lower cancer mortality.
A 10% increase in the restrictiveness of the policies led to an 8.5% decrease in rates
of combined alcohol attributable cancers.[10] Schwartz et al. reported significant association between alcohol sales and alcohol mortality which
persisted after controlling the tobacco use. Reducing alcohol consumption is a cost-effective
means of targeting cancer control, which has the potential to decrease the cancer
related mortality.[11]
Therefore, efforts should be directed towards individual, society, and legislative
level to reduce the consumption of alcohol to decrease both the cancer incidence and
the mortality.[12]
