Hepatocellular carcinoma incidence

Sirica AE, Wilkerson CS, Wu LL, et al. 1989. Evaluation of chlordecone in a two-stage model of hepatocarcinogenesis A significant sex difference in the hepatocellular carcinoma incidence. Carcinogenesis 10(6) 1047-1054. 

Tanaka, Y., Hanada, K., Mizokami, M., Yeo, A.E., Shih, J.W., Gojobori, T., and Alter, H.J. (2002). A comparison of the molecular clock of hepatitis C virus in United States and Japan predicts that hepatocellular carcinoma incidence in United States will increase over the next two decades. Proc. Natl. Acad. Sci. USA 99,15584-15589. 

Hepatocellular carcinoma (HCC) develops in patients with chronic liver diseases associated with hepatitis B and hepatitis C vims infections with high incidences. Here, an acyclic retinoid has been shown to suppress the posttherapeutic recurrence after interferon-y or glycerrhicin treatment in cirrhotic patients who underwent curative treatment of preceding tumors. The retinoid induced the disappearance of serum lectin-reactive a-fetoprotein (AFP-L3), a tumor marker indicating the presence of unrecognizable tumors in the remnant liver, suggesting a deletion of such minute (pre)malignant clones (clonal deletion). As a molecular mechanism of the clonal deletion, a novel mechanism of... 

In Greece, a case-control study was conducted to investigate the incidence of liver cancer by estimating the consumption of six types of flavonoids with a semiquantitative questionnaire on the frequency of foods. The intake of flavones was inversely associated with hepatocellular carcinoma, irrespective of its etiology (viral or nonviral). With respect to cholangiocarcinoma, an inverse association with the consumption of flavan-3-ols, anthocyanidins, and total flavonoids studied was found. However, this last result should be viewed with caution because of the small sample size, due to the fact that this is a rare type of cancer (Lagiou and others 2008). 

Both isomers of dimethylhydrazine have been shown to be carcinogenic in rodents following chronic oral exposure and 6-mon inhalation exposure to 1,1-dimethylhydrazine. Increased tumor incidence was observed in mice, although these findings are compromised by the contaminant exposure to dimethylnitrosamine. An increased incidence of lung tumors and hepatocellular carcinomas was also seen in rats but not in similarly exposed hamsters. The U.S. Environmental Protection Agency (U.S. EPA) inhalation slope factors are currently unavailable for dimethylhydrazine. 

Inhalation studies at the U.S. Air Force Aerospace Medical Research Laboratory showed an increased tumor response (hemangiosarcomas and Kupffer cell sarcomas) in mice exposed at 5 ppm, 6 h/d, 5 d/w for 6 mon (MacEwen and Vernot 1977, and Flaun 1977, reviewed in Trochimowicz 1994). Rats similarly exposed at 5 ppm exhibited increased incidences of squamous cell carcinomas of the lung and hepatocellular carcinomas. Hamsters subjected to a similar experimental protocol failed to show an increased incidence of tumors (MacEwen and Vernot 1975). It must be noted that the 1,1-dimethylhydrazine used in these studies contained 0.12% dimethylnitrosamine, which could be a significant confounder. 

Increased mortality, tremors, growth reduction elevated incidence of thyroid neoplasms and malignancies in all treated animals, but no hepatocellular carcinomas (IARC 1979 USEPA 1988)... 

A statistically significant increase in hepatocellular carcinomas was seen in male and female mice that were dosed with 590 and 1,179 mg/kg/day hexachloroethane in com oil by gavage for 78 continuous weeks (Weisburger 1977). The incidence of tumors in the exposed mice was greater than that in controls on the basis of both the Fisher Exact test and the Cochran-Armitage test. There were no hepatic tumors in male or female rats with chronic exposure to doses of 10-423 mg/kg/day (NTP 1977, 1989 Weisburger 1977). 

Chlordecone was also shown to be carcinogenic in rats and mice. The results of NCI (1976) bioassays in mice and rats clearly suggest that chlordecone induces hepatocellular carcinomas in both sexes of rats and mice. Administration of chlordecone to Osborne-Mendel rats via the diet for 80 weeks resulted in a significant increase in the incidence of hepatocellular carcinomas over pooled controls in both males and females at a time-weighted average of 1.2 mg/kg/day in males and 1.3 mg/kg/day in females (NCI 1976). In the NCI (1976) bioassay in rats, the incidence of hepatocellular carcinomas was significantly increased (p<0.05) in both with a dose-related trend. The incidence of hepatocellular carcinomas in high-dose males and females were 7% and 22% for males and females, respectively. 

A familial deficiency in the bile-acid export pump, 103 which conveys bile acids from hepatocyte cytoplasm into bile canaliculi, increases the incidence of hepatocellular carcinoma in children. 

In animal studies aldrin induced an increased incidence of hepatocellular carcinoma at two dietary doses in male mice the tumors showed a significant dose-response trend and were statistically significant at the high dose. Follicular cell tumors of the thyroid and adrenal cortical cell adenomas were increased in female rats in the low-dose group but not in the high-dose group the results could not be clearly associated with treatment. ... 

Rats fed diets containing 30 or 300ppm ammonium perfluorooctanoate for 2 years had increased liver weights with occasional necrosis and an apparent dose-dependent increase in Leydig cell adenomas, but there was no evidence of an increased incidence of hepatocellular carcinoma. In a follow-up study in male mice, 300ppm in the diet for 2 years caused increases in liver, Leydig cell, and pancreatic acinar cell tumors that may have been associated with the peroxisome-proliferating capabilities of the compound. Ammonium perfluorooctanoate also produced sustained increases in serum estradiol concentrations. ... 

Animal studies demonstrate that carbon tetrachloride produces hepatocellular carcinomas in the mouse, rat, and hamster." Mice administered 1250 or 2500mg/kg approached nearly a 100% incidence of hepatocellular carcinomas vs. 6% or less in various controls. Hamsters receiving 190 and 380mg/kg by gavage had a 100% liver cell carcinoma incidence for those animals surviving past week 43. ... 

At dosages above 30mg/kg in the diet, chlordane interfered with reproduction in rats and mice, but this effect was reversible after exposure ceased." Pre- and postnatal exposures to chlordane altered the development of the immune system in rodents. A dose-related increase in the incidence of hepatocellular carcinomas was found in male and female mice fed approximately 60mg/k chlordane for 80 weeks. In rats, increases in the incidences of thyroid follicular cell neoplasms were observed. ... 

Administered in the drinking water for 113 weeks, 42mg/l crotonaldehyde induced neoplastic lesions in rats 2 of 27 animals had hepatocellular carcinomas and 9 of 27 had neoplastic lesions. Altered liver cell foci occurred in 23 of the 27 animals. The increased incidence of neoplastic and preneoplastic lesions was not observed at the higher dose (421 mg/1). Crotonaldehyde produced variable results in a variety of genetic assays. ... 

There was also a dose-related trend for the incidence of hemangiosarcomas and mammary adenocarcinomas in female rats and hepatocellular carcinoma in male mice. High mortality in all animal groups obscured results. The National Cancer Institute determined that there was no conclusive evidence for carcinogenicity, but 1,1-dichloroethane should be treated with caution by analogy to other chloroethanes shown to be carcinogenic in laboratory animals. ... 

No excess of cancer was reported in two follow-up smdies of affected individuals in Turkey about 20-30 years after consumption of contaminated grain had ceased. " In mice, liver tumors were observed after exposure to HCB at 12-24mg/kg/day in the diet, but not at 6mg/kg/day. Hepatomas, hepatocellular carcinomas, bile duct adenomas, and renal cell adenomas were observed in rats after dietary administration." Liver tumors were also observed in 100% of surviving females and 16% of males after dietary administration to rats for 90 weeks. In another study, increased incidence of parathyroid adenomas and adrenal pheochromocytomas were observed in male and female rats and liver neoplastic nodules in females of the Ei generation in a two-generation feeding study. 

Gavage administration of 590 and 1179mg/kg/day to mice for 78 weeks caused a significant increase in the incidence of hepatocellular carcinomas, whereas no increase in these tumors was observed in rats given 212 or 423 mg/kg/day. A nonsignificant increase in renal tumors was seen in rats, and tubular nephropathy occurred in both species. In 2-... 

Macaque monkeys given weekly intraperi-toneal injections of 40mg NDPA for a total dose of 70g had a higher incidence of hepatocellular carcinomas (6/6) compared with that of historical controls (7/90). ... 

Mice were administered 250 or 500mg/ kg/day pentachloroethane by gavage for life. The hepatic carcinogenicity of pentachloroethane was clearly established despite reduced survival rates. The incidence of hepatocellular carcinomas was significantly increased in low-dose males and in treated females there also was a significant dose-related increase in the incidence of hepatocellular adenomas in treated females. ... 

It has been suggested that the mechanism of action of pentachloroethane may be similar to that of other chlorohydrocarbons that also induce a high incidence of hepatocellular carcinoma in mice and have little or no carcinogenic effect in rats. The carcinogenic potential may be mediated through the active metabolic intermediates trichloroethylene and tetra-chloroethylene, which are formed in some species but not in others. 

Large gavage doses, approximately 500 and lOOOmg/kg per day for 78 weeks, caused a statistically significant increase in the incidence of hepatocellular carcinomas in mice. Inhalation exposure by rats to 200 or 400 ppm for 2 years caused an increased incidence of mononuclear cell leukemia a dose-related trend for a rare renal tubular neoplasm was observed in males. ... 

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