PCBs may cause Liver Cancer in Humans
| Introduction
Liver damage is one of the clear signs of PCB poisoning in humans (see Liver Damage). Over time, this damage may include development of liver cancers (also known as hepatobiliary tumors, hepatomas, or hepatocellular carcinomas.) Scientists are beginning to understand the mechanisms behind these cancers. They suspect that when PCBs stimulate the production of liver enzymes this promotes the growth of dormant cancers started by other causes, resulting in liver cancer. Some studies indicate that PCBs interact with other known food contaminants, such as nitrosamines created by meat preservatives and tobacco, to produce cancer. PCBs, or PCB breakdown products, also damage and kill liver cells directly, alter the way our bodies make and use fats in the bloodstream, and interact with important chemical receptors in the cells, all of which may be linked to cancer cell growth. |
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Summary of Studies Linking PCBs and Liver Cancer
(Each entry represents one finding in a study. Some studies had multiple findings.)
The 27 human studies listed below show links between PCBs and cancer of the liver, gallbladder and biliary tract. (Many more animal studies prove that PCBs cause liver cancer in animals.) Keep in mind that not all studies are equal in size or quality.
- study found a statistically significant excess in deaths from liver cancer (primary and unspecified), gall bladder and biliary tract
- most excess deaths occurred in women
- within 4 years, 12 of 2061 PCB poisoned Taiwanese died from hepatoma (liver cancer), liver cirrhosis or liver diseases with hepatomegaly --- half of all deaths
- 2 of 12 autopsied Japanese PCB victims showed liver cancer
- 2 cases of liver and bile duct cancer
- overall cancer mortality was greater than expected in male Japanese PCB poisoning victims
- liver cancer risk was consistently high in both men and women during the entire 16-year observation period.
- even after a 9-year latent period, the risk of liver cancer in males was significant
- close structural similarity of furans to dioxins, especially 2,3,7,8-TCDD which is a proven animal carcinogen, raises concern as to the potential carcinogenicity of furans [PCBs are generally contaminated with furans]
- nonneoplastic hepatotoxic effects (primarily fatty metamorphosis and necrosis) were concentration-related
- PCBs as the components of the furans may also have been responsible for the statistically significant liver cancers
- study 1 ---five liver and biliary cancer deaths observed in workers, where 1.9 would have been expected (4 out of 5 were female).
- study 2 --- among male workers, cancers of the gastrointestinal tract (including liver cancer) were significantly increased (6 observed, 2.2 expected).
- study 3 --- almost five-fold significantly elevated risk of primary liver cancer in Yusho PCB victims (Japan)
- available studies suggest an association between cancer and exposure to PCBs.
- increased risk from hepatobiliary (liver or bile duct) cancer emerged consistently in different studies.
- ultrasonic and tumour marker examination of two series of 79 and 125 patients with 'Yusho' disease in 1983 and 1984, respectively, did not reveal any case of hepatic-cell carcinoma
- because the numbers were small, dose-response relationships could not be evaluated, and the role of compounds other than PCBs could not be excluded, the evidence was considered to be limited
- patient mortality due to malignant neoplasms suggested an excess of cancer induced deaths.
- both PCBs and furans are well known toxic agents to the liver with severe necrosis expected and the risk of cancer possible.
- liver function tests failed to reveal any serious liver lesions in the patients
- systemic dysfunctions included liver enzyme induction and abnormal lipid metabolism
- increased incidence of cancer of the liver and of the biliary tract
- toxicity is probably mediated through interaction with the Ah receptor, and they are potent inducers of certain cytochrome enzymes
- typical toxic effects of PCBs, such as tumour promotion, are caused by PCB congeners in all of these three classes
- PCB congeners are metabolized to yield hydroxy- and methyl sulphone metabolites
- epidemiological studies of occupationally-exposed workers have indicated an increased incidence of cancer of the liver and of the biliary tract
- it appears that any level of PCB exposure may be injurious to human health.
- the most consistent tissue modification has been a marked hypertrophy of the liver.
- tumors in patients who inadvertently consumed PCBs in 1968 included one or more occurrences of liver cancer
- human mortality studies provide strong evidence that PCBs produce cancer of the liver, biliary tract, and gallbladder
- induction of liver enzymes have been consistently observed in humans
- no conclusive evidence of human liver cancer resulting from occupational exposure to PCBs has been obtained. [An occupational PCB liver cancer study was published the same year by Brown, see above.]
- PCBs impaired liver function in humans
- several occupational studies show cancer mortality rates for exposed workers were significantly elevated for cancers of the liver, biliary tract and gallbladder
- PCB exposure is rarely limited to a single congener, therefore, the review dealt with the effects of complex mixtures of PCBs, possibly containing dioxins and furans
- for practical purposes, PCBs should be regarded as if they were carcinogenic to humans
- almost without exception, PCBs contain various levels of furans as contaminants
- epidemiologic studies have suggested that exposure to PCBs can cause liver cancer
- PCBs are metabolized and excreted primarily through the liver and kidneys
- Several epidemiologic studies of both occupational PCB exposure and accidental PCB intoxication suggest PCBs might be a potent carcinogen in the liver
- PCBs which induce the enzyme P-450 may promote tumors by inhibiting intercellular communication and/or by stimulating cell proliferation.
- Furans are attracted to cells in the liver and lungs.
- Furans induce necrosis (cell death) and epoxide formation to their target cells, which might result in carcinogenesis of liver and lungs.
- certain PCBs are classified with dioxins by the World Health Organization [they have declared dioxin a known human carcinogen]
- PCB contribution to cancer risk may only now start to appear, due to long human cancer latency and the nature of tumor promotion
- PCBs promote liver tumors by triggering the early appearance of tumors which have been initiated but would normally lay dormant and appear only in old age --- ie: cancers occur at younger ages due to PCBs
- liver tumors required a "start-up" chemical before PCBs could promote the tumors, in this case nitrosames (a common byproduct of meat preservatives & tobacco)
- dioxin (TCDD) is known to cause hepatocellular carcinomas (certain PCBs are dioxin-like)
- PCBs are associated with hepatocellular carcinomas (liver cancers) in humans
- PCBs have tumor promoter effects
- liver cancers in rats were used to extrapolate human cancer risks in 1984
- several studies have demonstrated the carcinogenic potential of PCB mixtures.
- PCBs ingested with food may play a role in inducing primary cancer of the liver
- subliminal quantities of potential hepatocarcinogens may play a synergistic role with high fat diets
- simultaneous smoking and alcohol intake may have a co-carcinogenic role
- PCB damage may not be contingent on binding to the aromatic halogenated hydrocarbon (AHH) receptor
- non-coplaner PCB congeners are not necessarily wholly responsible for the liver carcinogen properties of PCBs
- certain PCBs have toxicities in human tissues comparable to dioxin
- genetic cancer susceptibilities in humans may be similar to those reported among mouse strains
- certain genetic characteristics in fish are very similar to human genes, and may mark a susceptibility for liver cancer when exposed to PCBs
- certain PCBs have an estrogenic (hormonal) effect on human liver cancer cells [which may stimulate tumor growth]
- together, several types of PCBs have additive estrogenic effects
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