Page last updated: Wednesday, November 19, 2008
Recent research about alcohol and colorectal cancer
Creina S. Stockley, The Australian Wine Research Institute
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 DNA.

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 liver’s 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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