Environmental factors and risk for liver cancer (hepatocellular carcinoma)
July 3, 2005 | 12:00am
Dietary Aflatoxins |
These data suggest a synergism (greater than the multiplicative product of individual exposure effects) between HBV and dietary aflatoxin in the causation of HCC. Confirmatory results were noted in cohort studies conducted among other aflatoxin-exposed populations. There is some evidence that genetically determined individual differences in aflatoxin metabolism are important code-terminants of risk in aflatoxin-exposed individuals. Singapore and Shanghai historically are high-risk areas for HCC, both of which have been experiencing steadily decreasing incidence rates over the past 2 decades. Singapore is an island nation in Southeast Asia that has seen tremendous economic progress since its independence in 1965. The decrease in aflatoxin contamination in the food supply as a result of economic development is a likely contributor, at least in part, to the decreasing burden of liver cancer in this newly affluent country. There is a relatively short time interval between the countrys increase in living standards and its liver cancer rate decrease, suggesting that aflatoxins exert a major effect on late-stage carcinogenesis. In China, economic reform began in the 1980s. Again, liver cancer rates in Shanghai began to decrease shortly after its residents increase in standard of living.
There is a little information on whether aflatoxins are related to cases of HCC in the United States. It is intriguing that in a pilot study, tumor tissues from 3 of 19 patients with HCC were positive for aflatoxin B1-DNA adducts and 5 of 5 patients tested for aflatoxin B1-albumin adducts in serum yielded positive results.
Multiple chemical components of cigarette smoke are hepatic carcinogens in animals. Although results are not totally consistent, a number of case-control and cohort studies in diverse populations have implicated cigarette smoking as a causal risk factor for HCC. However, given the strong positive correlation between the use of tobacco and alcohol in based epidemiologic data are considered by many to be inconclusive in establishing a causal role for tobacco in the pathogenesis of HCC.
In a separate cohort study, the same group of investigators showed that plasma level of selenium at baseline inversely predicted risk, especially among subjects exhibiting low levels of serum retinol. The latter cohort study also showed that the positive association between alcohol drinking and risk for HCC was observed only among subjects exhibiting low (i.e., <population median) levels of plasma carotenoids (B-carotene -carotene, and lycopene). In a prospective cohort study of 70 cirrhotic patients in Italy, baseline serum retinol levels were significantly lower in incident cases of HCC compared with cirrhotic patients who remained free of the disease after 7 years of follow-up evaluation. Finally, in a randomized controlled trial involving 89 patients who were disease free after curative treatment, those receiving an oral administration of a synthetic retinoid on a daily basis for 12 months had significantly fewer second primary HCCs and experienced significantly longer survival compared with the placebo group, after a median follow-up time of 62 months.
In contrast, studies conducted in high-risk Asian and African women uniformly yielded null results. These seemingly disparate observations can be explained if the combined effects of viral (i.e., HBV) and hormonal (i.e., estrogen) factors on the pathogenesis of HCC were not synergistic, but simply the sum of their individual effects. Under this assumption, a sample size many times larger than those used in the Asian and African studies would be required to detect the additional risk in oral contraceptive users (-2- to 3-fold) against the very high background relative risk (>20-fold) in HBV carriers. There is sparse information on the use of replacement hormones and risk for HCC. The available epidemiologic evidence does not suggest an association.
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