Cells that are overwhelmed by injury and insult can simply autodigest,
that is, necrose. Apotosis is, however, programmed cell death,
where the cell is damaged or mutated and fragments into membrane
bound fragments for degradation by other cells. The body automatically
replaces the cell. Cancer may occur either when the damaged cell
fails to undergo apotosis and proliferates or when the replaced
cell is also mutated and proliferates; proliferating cells are
most at risk of genotoxic damage. Thus, cancer is basically when
the rate of proliferation of mutated cells greatly exceeds the
rate of apotosis.
Alcohol can cause either necrosis or apotosis, directly or indirectly,
which may have positive or negative effects. For example, a positive
effect is that alcohol can directly stimulate the death of damaged
cells that may lead to cancer, while a negative effect is that
alcohol can directly mutate critical genes and stimulate their
proliferation. Cancers linked to alcohol consumption include:
breast cancer indirectly due to the alcohol-stimulated hepatic
metabolism of estrogen; hepatic cancer due to direct cell mutation
and proliferation; and aerodigestive tract cancers such as oesophageal
cancer due to cell mutation and synergy with other injuries from,
for example, gastric acid. Concerning oesophageal cancer, 25-68%
are attributable to alcohol consumption where consumption of more
than 160 g alcohol per day ( recommended daily guidelines are
below 30g) increases the risk by 10-fold, and 80% of cases are
preventable by abstinence from both alcohol and cigarette smoking.
Poor diet and oral hygiene are also co-risk factors.
Of all lifestyle factors related to cancer, alcohol is a modest
attributable risk at 4-6%, while the attributable risk for cigarette
smoking is approximately 30% and that for diet is 20-50% (Doll
et al. 1998).
In Australia, colorectal cancer is the second most common cause
of death from cancer in women (after breast cancer) and men (after
lung cancer); it usually develops from a small benign growth or
adenoma in the mucosa of the colon or rectum. There is inconsistent
evidence, however, directly linking alcohol consumption to colorectal
cancer (Kune and Vietta 1992, Potter et al. 1996). For example,
while a Swedish population-based study did not observe an increase
risk of colorectal cancer overall or at specific anatomical sites
in alcoholics followed for 25 years (Ye et al. 2003), a French
case-controlled study did observe a relationship between alcoholism
and the risk of adenomas and colorectal cancer (Bardou et al.
2002), where alcohol promotes the growth of the adenoma and hence
promotes colorectal carcinogenesis. A six-year Canadian population-based
study also observed an increased risk of colorectal cancer in
men, particularly for the distal colon and rectum (Sharpe et al.
2002). When the type of beverage was considered in this study,
beer showed the strongest association with colorectal cancer while
wine showed the weakest association. Indeed, some other studies
that also observed a link between alcohol consumption and colorectal
cancer, also observed beverage specific effects on the risk colorectal
cancer. A recently published study by Pederson et al. (2003) has
drawn similar conclusions to that drawn by Stemmermann et al.
(1990), Kune et al. (1992), Goldbohm et al. (1994) and Hsing et
al (1998). These five studies suggest that while beer consumption
clearly increases the risk of colorectal cancer, the association
is less clear for wine and spirits. Furthermore, the 14-year Danish
population-based study observed that while alcohol, and in particular,
beer consumption significantly increased the risk of rectal cancer,
the risk appeared to be reduced when wine was consumed (Pedersen
et al. 2003). The components of wine most likely to be responsible
for an anti-carcinogenic effect are phenolic compounds. Resveratrol,
for example, has been observed to depress the growth of colorectal
aberrant crypt foci in rats (Schneider et al. 2000) and anthocyanins
have been observed to inhibit the growth of human colon cancer
cells (Kamei et al. 1998).
In the all the studies cited above the amount of alcohol consumed
also correlated with the risk of colorectal cancer (Munoz et al.
1998), but the level of alcohol consumption that increases the
risk has not been determined and there are usually other risk
factors for cancer that confound determination (Longnecker 1995).
For example, it has been suggested that alcohol consumption and
folate deficiency have a synergistic action in the promotion of
colorectal cancer, particularly in alcoholics who have a low intake
of folate (Giovannucci et al. 1998, Su et al. 2001). Flood et
al. (2002), however, did not observe an increased risk of colorectal
cancer with combinations of high alcohol consumption and low folate
intake; folate is involved in the synthesis and methylation of
A number of mechanisms have been suggested for the potential carcinogenic
effects of alcohol on the colon and rectum. For example, colorectal
cancer may occur from the altered metabolism of genotoxic compounds
in the liver, such as nitrosamines, by alcohol (Swann et al. 1984,
Hakkak et al. 1996), as alcohol can either induce or suppress
the livers microsomal monooxygenase (metabolizing) system. Beer
and spirits can contain nitrosamines. In addition, acetaldehyde,
which is the first metabolite or breakdown product of alcohol,
has been classified as a carcinogen in animals by the International
Agency for Research on Cancer. In saliva, the digestive tract
and colon, the further breakdown of acetaldehyde to acetate is
limited (Salaspuro 1996). Consequently, these areas generally
have a high localised concentration of acetaldehyde. This concentration
is even higher in heavy consumers of alcohol, who have been shown
to be at greater risk of developing cancers of the mouth, digestive
tract and colon.
Recent epidemiological studies also suggest that the risk of alcohol-associated
digestive tract cancers is significantly increased in Asian alcoholics
who have the inactive aldehyde dehydrogenase (ALDH2) enzyme (Yokoyama
et al. 1998) and in Caucasian alcoholics who have the very active
alcohol dehydrogenase (ADH31) enzyme, where both population groups
have a higher concentration of acetaldehyde in their saliva, digestive
tract and colon for a longer period of time than the general population.
Indeed these studies imply that acetaldehyde may be a local and
topical carcinogen in humans.
In summary, this recent research suggests that there may be a
casual relationship between alcohol consumption and colorectal
cancer, especially for heavy and excessive consumers of alcoholic
beverages such as beer, although any effect of alcohol on carcinogenesis
appears to be indirect. This research also suggests that the moderate
consumption of wine may reduce the risk of colorectal cancer.
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