Risk Of Primary Liver Cancer Research Articles

Primary liver cancer and renal cell carcinoma in laundry and dry-cleaning workers in Denmark.

Previous studies have shown an excess risk of primary liver cancer among women working in laundries and dry-cleaning shops in Denmark at the time of the census in 1970. During the period 1970-1987, 14 cases of primary liver cancer were observed (standardized mortality ratio 2.7, 95% confidence interval 1.5-4.5). A nested case-referent study was undertaken in order to classify laundry workers and dry-cleaning workers separately. According to hints in the literature, renal-cell carcinomas were also included in this analysis. Original census forms from 1970 were retrieved from the Danish National Record Office for the 17 cases with primary liver cancer and the 16 cases with renal-cell carcinoma and five matched referents per case. All of the 17 patients with primary liver cancer worked in laundries in 1970, whereas only 74% of the referents worked in laundries. Neither was the risk of renal-cell carcinoma associated with dry-cleaning work (relative risk 0.7, 95% CI 0.2-2.6). The excess risk of primary liver cancer observed for women working in laundries and dry-cleaning shops in Denmark is not likely to be explained by exposure to dry-cleaning solvents. Excessive alcohol consumption is not a likely explanation either, and the excess risk therefore remains unexplained.

Primary liver cancer and survival in patients undergoing liver transplantation for hemochromatosis

Cirrhotic patients with hereditary hemochromatosis (HHC) have an increased risk of primary liver cancer (PLC). The purpose of this study was to determine the prevalence of primary liver cancer in patients with HHC undergoing orthotopic liver transplantation (OLT). Five liver transplant centers were surveyed; clinical and pathological data on 37 patients with HHC undergoing OLT were retrospectively collected and analyzed. The diagnosis of HHC was established by a combination of serum transferrin-iron saturation, hepatic iron index (HII), and/or pattern of liver iron staining. The diagnosis of HHC had been unsuspected before OLT in 13 of 37 (35%). Primary liver cancer was found in the explants of 10 of 37 patients (27%) and was unsuspected in 7 of 10 (70%); 8 were hepatocellular carcinoma, and 2 were cholangiocarcinoma; foci of hepatocyte dysplasia were found in 6 additional patients. Mean (+/- SEM) hepatic iron content and HII in 20 patients without prior phlebotomy or bleeding were 17.2 mg/g dry weight (+/- 2.9) and 5.5 (+/- 0.8), respectively. The overall 1-year survival rate after OLT in the 37 HHC patients was 58% (v 55% for HHC patients with PLC). We draw the following conclusions: (1) the diagnosis of HHC is often unsuspected before OLT, and HHC should be evaluated pretransplantation by direct and indirect markers; (2) HHC patients undergoing OLT have a high prevalence of primary liver cancer, the majority being unsuspected; and (3) HHC patients have poorer than average survival after OLT, which cannot be explained solely by the presence of concomitant PLC.

Cancer risk following primary hemochromatosis: A population‐based cohort study in Denmark

A population-based cohort of 120 Danish men, discharged with a hospital diagnosis of primary hemochromatosis from 1977 to 1989, was followed up to 1989 for subsequent cancer risk. Nineteen subjects (including 6 with primary liver cancers) were excluded from the analysis, either because they died within the same month of hemochromatosis diagnosis or because they had cancer prior to diagnosis of hemochromatosis. Among the 101 remaining subjects, 4 primary liver cancers occurred one year or more after the diagnosis of hemochromatosis, far surpassing the expected number based on incidence rates from the Danish population (standardized incidence ratio 92.9, 95% confidence interval 25.0 to 237.9). The excess of liver cancer was associated with cirrhosis and included cholangiocarcinoma as well as hepatocellular carcinoma. Significantly elevated risks were also observed for non-hepatic cancers (13 cases; SIR 3.5, 95% CI 1.9 to 6.0), notably esophageal cancer (2 cases; SIR 42.9, 95% CI 4.8 to 154.9) and skin melanoma (2 cases; SIR 27.8, 95% CI 3.1 to 100.3). The results of this population-based study are in accordance with the hypothesis that patients with primary hemochromatosis have a substantial risk of primary liver cancer. Further studies of hemochromatosis may be useful in clarifying the relation of non-hepatic malignancies to body iron stores in the general population.

Mortality follow-up of the 1942 epidemic of hepatitis B in the U.S. Army.

The hypothesis that adult infection with the hepatitis B virus in the United States leads to a carrier state with a high risk of primary liver cancer was tested in two ways: (a) a cohort mortality study of U.S. Army veterans given yellow fever vaccine contaminated with hepatitis B virus in 1942 and controls and (b) a case-control study comparing veterans with hepatocellular carcinoma in Veterans Affairs hospitals with matched controls with respect to receipt of contaminated vaccine in 1942. Three groups totaling 69,988 men were the subjects of the cohort study: group 1 comprised men hospitalized with hepatitis in 1942, group 2 comprised men subclinically infected in 1942 and group 3 comprised controls who entered service after the contaminated vaccine was discontinued. Hepatocellular carcinoma cases (n = 24) and control subjects (n = 63) derived from Veterans Affairs hospital discharge files were the subjects of the case-control study. Group comparisons of death rates from liver cancer were refined by expert review of records to select hepatocellular carcinoma from among all causes of death so diagnosed in the cohort study. Slightly excess mortality was found for hepatocellular carcinoma in group 2 (subclinical hepatitis B) but not for group 1 (overt hepatitis B) compared with group 3 (controls) (p = 0.08). Mortality from nonalcoholic chronic liver disease was less in group 2 than in group 3. In the case-control study, the relative risk for hepatocellular carcinoma conferred by receipt of contaminated vaccine was estimated as 3.3 (p = 0.06). We conclude from the cohort study that immunocompetent adult males rarely become carriers after hepatitis B virus infection, probably far less often than the frequently assumed rate of 5% to 10%. The small excess liver cancer mortality seen in the cohort study and the results of the case-control study are consistent, nevertheless, with the now well-established etiological role of hepatitis B virus infection in liver cancer.

Occupational risks for primary liver cancer in Shanghai, China.

Using occupational data for over 3,400 primary liver cancer cases diagnosed between 1980 and 1984 reported to the Shanghai Cancer Registry, and employment information from the 1982 census for the Shanghai population, standardized incidence ratios were computed to generate leads to occupational risks of liver cancer. Among men, a statistically significant excess number of cases was observed for chemical processors, textile workers, wood workers, blacksmiths and machine-tool operators, and material handlers and dock workers. Increased incidence of liver cancer also was observed among female transport equipment operators. These findings indicate that a number of similar occupations are associated with increased risk of primary liver cancer in western countries and China. Although causal inferences cannot be drawn from these data, our study adds to the limited evidence of the potential role of occupational exposures in liver carcinogenesis.

Reproductive factors and the risk of hepatocellular carcinoma in women.

The relationship between reproductive factors and the risk of primary liver cancer was analyzed using data of a case-control study conducted in Northern Italy between 1984 and 1991 on 79 women with histologically or serologically confirmed hepatocellular carcinoma and 344 controls in hospital for a wide spectrum of acute, non-neoplastic diseases. The multivariate relative risk (RR) for parous vs. nulliparous women was 2.6 (95% confidence interval (CI) 1.2 to 5.8), and the risk increased with parity from 2.1 for 1, to 2.6 for 2, to 3.2 for 3, to 3.5 for 4 or more births (chi 2(1) trend = 6.49, p = 0.01). The relative risks were above unity, though not significantly, in women reporting spontaneous (RR = 1.3) and induced (RR = 1.6) abortions, and there was a significant trend in risk with total number of abortions. An apparent inverse trend in risk with age and first birth was accounted for by parity. No relationship emerged with age at menarche, at menopause or other menstrual factors. The association between parity and hepatocellular carcinoma was, if anything, more marked at older ages, since the RR was 1.6 (95% CI 0.5 to 4.6) below age 60, and 4.8 (95% CI 1.3 to 18.1) at age 60 or over. This observation has relevant public-health implications, since in developed countries primary liver cancer is extremely rare among young women, but not at older ages. The association between parity and hepatocellular carcinoma is similar to that described for combined oral contraceptives, again confirming that the impact of contraceptives on the risk of several neoplasms is similar to that of pregnancy.

Lack of increase in heterozygous alpha 1-antitrypsin deficiency phenotypes among patients with hepatocellular and bile duct carcinoma.

Homozygous alpha 1-antitrypsin deficiency (PiZZ phenotype) is known to be associated with increased risk of cirrhosis and primary liver cancer. Although a relationship between heterozygous alpha 1-antitrypsin deficiency and chronic liver disease was suggested recently, it is still a matter of controversy whether such patients are at increased risk of liver cancer. The goal of this study was to determine the prevalence of heterozygous alpha 1-antitrypsin deficiency of different phenotypes among patients with primary hepatobiliary cancers. We studied 82 patients with primary hepatobiliary cancer; 59 had hepatocellular carcinoma and 23 had bile duct carcinoma. alpha 1-Antitrypsin quantitation and phenotyping were performed in each patient using standard methods. The distribution of the various Pi phenotypes was compared with that found in a normal population and reported elsewhere. Odds-ratio and chi 2 tests were used to measure the relative risk and the significance of association, respectively, between primary hepatobiliary cancers and heterozygous alpha 1-antitrypsin deficiency. Four patients in each of the cancer groups were heterozygous. Among the hepatocellular carcinoma patients, three had the PiMS phenotype and one had the PiMZ phenotype. Of these four heterozygous patients, only two had cirrhosis; one had cryptogenic cirrhosis and the other had hepatitis B virus-related cirrhosis. One noncirrhotic patient with a PiMZ phenotype had a fibrolamellar carcinoma. Of the four patients with bile duct carcinoma, three had the PiMS phenotype and one had the PiMZ phenotype. Of the four heterozygous patients, two had primary sclerosing cholangitis without associated inflammatory bowel disease and one patient had had previous biliary operations.(ABSTRACT TRUNCATED AT 250 WORDS)

Oral contraceptives and primary liver cancer among young women.

The association of oral contraceptive use with liver cancer was examined in a study of 76 deaths from primary liver cancer, 22 deaths from cancer of the intrahepatic bile ducts, and 629 controls among women aged 25 to 49 years. The subjects in the study are from the 1986 National Mortality Followback Survey, which included a questionnaire sent or administered to the next-of-kin of almost 20,000 deceased individuals in the United States. Information on a number of lifestyle factors was collected, including questions on oral contraceptive use. Increased risks of primary liver cancer were found for ever-users (odds ratio [OR] = 1.6, 95 percent confidence interval [CI] = 0.9-2.6), and for long-term (greater than or equal to 10 years) users (OR = 2.0, CI = 0.8-4.8) of oral contraceptives. When the analysis was restricted to subjects whose spouse or parent was the respondent, more pronounced risks were seen for ever-users (OR = 2.7, CI = 1.4-5.3) and long-term users (OR = 4.8, CI = 1.7-14.0). No clear excess risk was found for cancer of the intrahepatic bile ducts. This study, the largest to date, adds to the number of investigations demonstrating an increased risk of primary liver cancer with use, particularly long-term use, of oral contraceptives.

Determination of exposure to aflatoxins among Danish workers in animal-feed production through the analysis of aflatoxin B1 adducts to serum albumin.

Aflatoxin B1 is suspected as an etiologic factor in the increased risk for primary liver cancer among workers in animal-feed processing plants in Denmark. Aflatoxin bound to serum albumin was therefore measured for feed-processing workers. Blood samples were collected immediately after vacation and after four weeks of work, and aflatoxin was quantified by competitive enzyme-linked immunosorbant assay. Seven of 45 individuals with an estimated exposure of 64 ng aflatoxin B1.d-1.kg-1 body weight were positive. Three positive workers had been unloading a cargo with an aflatoxin B1 level of 26 micrograms.kg-1 raw material. The exposure level correlated well with the job titles. Dust samples collected at different sites showed considerable variation in the amount of aflatoxin B1 (nondetectable to 8 micrograms.kg-1 dust). The exposure to aflatoxin B1 may only partially explain the increased risk of liver cancer.

Cigarette smoking and liver cancer among US veterans

The relationship of tobacco use with risk of primary liver cancer was investigated using data from a 26-year mortality follow-up of nearly 250,000 US veterans, mostly from World War I. Significantly increased risks for liver cancer (289 deaths) were associated with most forms of tobacco use, including pipe and cigar smoking. Elevated relative risks (RRs) were seen for current cigarette smokers (RR = 2.4; 95 percent confidence interval [CI] 1.6-3.5) and former cigarette smokers (RR = 1.9, 1.2-2.9). A strong dose-response relationship (P less than 0.001) was found for cigarette smoking, with smokers of 40 or more cigarettes per day having almost a fourfold risk (RR = 3.8, 1.9-8.0). Risks were also found to increase significantly with years of cigarette use and with earlier age at the start of cigarette smoking. These results are consistent with those of other cohort and case-control studies, suggesting that cigarette smoking may be related to the risk of liver cancer.

Although Primary Liver Cancer Remains Rare, Pill Use Appears to Increase Risk in Women Under 50

This paper presents the findings of a study investigating the risk of primary liver cancer among oral contraceptive (OC) users aged under 50 years in the US. This case-control study was conducted at 17 hospitals in five US cities during 1977-85. Conditional logistic regression analyses were used to calculate the relative risks that controlled for the matching factors--age year of interview and geographic location of the hospital. The findings suggest that OC use increases the risk of hepatocellular carcinoma but it is implied that the risk was probably an initiating one rather than a promoting one. Nevertheless despite the large number of women under age 50 in the US who have used OCs at some time the actual number of cases of liver cancer attributable to OC use is relatively small and therefore has no public health importance in the US and other Western nations.

Women Who Use the Pill May be at Increased Risk of Primary Liver Cancer

Women Who Use the Pill May be at Increased Risk of Primary Liver Cancer

Primary liver cancer among women in laundry and dry-cleaning work in Denmark.

Tetrachloroethylene has been the most commonly used solvent in dry cleaning in Denmark since the late 1950s. A cohort of laundry and dry-cleaning workers was identified from the Danish Occupational Cancer Register for the study of cancer incidence of persons exposed to tetrachloroethylene. The Register includes cancer incidence data for a 10-year period for 8567 women and 2033 men employed in laundry and dry-cleaning in 1970. A significant excess risk was found for primary liver cancer among the women, with 7 observed and 2.1 expected cases (standardized incidence ratio 3.4, 95% confidence interval 1.4-7.0). No case of primary liver cancer was observed among the men, for whom the expected value was 1.1. The excess risk of primary liver cancer among the women is unlikely to be explained exclusively by excess alcohol consumption.

Occupational and non-occupational risk factors in relation to an excess of primary liver cancer observed among residents of Brooklyn, New York

The incidence and mortality rates of primary liver cancer (PLC) among residents of Brooklyn, New York, were studied for 1976 through 1983. Standardized race and sex-specific incidence and mortality rates and rate ratios were computed and compared with overall US rates as reported by the Surveillance, Epidemiology, and End Results (SEER) program. The results indicate a significant excess of PLC among all race and sex groupings. A comparison of the degree of agreement between incidence and mortality data for Brooklyn residents showed excellent agreement among male patients with PLC and adequate agreement among female patients with PLC. Next, the effect of occupation on PLC mortality among Brooklyn residents was assessed. Specific occupations found to be at excess risk for PLC are private household workers (ratio of observed to expected cases [O/E] = 4.34; P less than 0.0001), non-domestic cleaning and food and beverage service workers (O/E = 2.59; P less than 0.0001), protective service workers (O/E = 1.78; P = 0.035), and transport equipment operatives (O/E = 1.52; P = 0.027). Since the distribution of Brooklyn workers employed in these occupations was found to be similar to the distribution of all US workers employed in these occupations, it is unlikely that these occupational risk factors can explain the observed excess of PLC among Brooklyn residents. The effects of non-occupational risk factors for PLC were then assessed using multiple regression analysis. The only non-occupational risk factor found to be associated with PLC among Brooklyn residents was cirrhosis of the liver (P = 0.0072). It is interesting that of the four occupations found to be at excess risk for PLC in this study, three have been previously shown to be at excess risk for cirrhosis mortality. Moreover, Brooklyn residents have cirrhosis mortality rates that are approximately two times higher than US rates. These facts, coupled with the findings of this study, support the hypothesis that the excess of PLC observed among Brooklyn residents might be related to an excess of cirrhosis of the liver in the same population, and thus provide support for an etiologic role of cirrhosis in the pathogenesis of PLC.

Increased risk for primary liver cancer among women exposed to solvents.

An earlier case-referent study by the same authors [Int Arch Occup Environ Health 54 (1984) 147-153] reported that solvent-exposed women, but not men, had an increased risk for primary liver cancer. The present study was undertaken to verify these results. The relatives of deceased patients, ie, 377 liver cancer cases, 385 coronary infarction referents, and 476 stomach cancer referents, responded to a questionnaire on past employment and potentially relevant covariables, the response rates being 71.7, 72.7, and 69.0%, respectively. The information was assessed for solvent exposure by two occupational hygienists without knowledge of the patients' diagnoses. Seven male and seven female liver cancer cases had been exposed to solvents, the odds ratio being less than 1 for the men but greater than 3 for the women irrespective of the reference group used for comparison. The results confirm the authors' earlier findings. When both materials were combined, the odds ratio was 7.8 for the female liver cancer cases as compared with the infarction referents. In the combined material, nine female liver cancer cases, two stomach cancer referents, but no infarction referent had had at least probable exposure to chlorinated hydrocarbons. Such exposure was rare among all of the men in the study. This finding may explain why the increased liver cancer risk occurred only for the women, although a sex difference in sensitivity cannot be completely ruled out.

Cigarette smoking, alcohol consumption and primary liver cancer: a case-control study in the USA.

Cigarette smoking and alcohol consumption were examined as potential risk factors in a case-control study of primary liver cancer (PLC). A total of 165 PLC cases and 465 matched controls from several US hospitals were studied. A weak but statistically significant (p less than 0.05) dose-response relationship was observed between alcohol consumption and PLC in elderly females independent of other major risk factors (adjusted OR = 1.87 and 3.48 for 1-2 and greater than 3 drinks per day, respectively) and a similar trend was evident in elderly males. The risk for PLC was also elevated in elderly females who were current cigarette smokers (adjusted OR = 3.30). Our results suggest that alcohol consumption and cigarette smoking may have minor age- and sex-specific effects on the development of PLC, and underscore the need for further investigations to elucidate major PLC risk factors in US populations.

Primary Liver Cancer in Côte d'Or (France)

The registry of digestive tract tumours established for the department of Cote d'Or (France) was used to study the incidence and some of the characteristics of primary liver cancer (PLC) in this area. The annual age-standardized incidence rate was 7.6/100,000 for males, and 1.8/100,000 for females. As compared to other areas the Cote d'Or is in the intermediate incidence areas. The risk of PLC was higher in urban than in rural areas in men (p less than 0.01). There was no significant variation in PLC incidence over the eight years of the study. Alfafoetoprotein levels over 200 ng/ml were observed in only 48.9% of the cases. Alfafoetoprotein measurement has to be complemented by other investigations in screening of high-risk patients. Liver cirrhosis was present in 70.9% of the cases in which the information was available. The male:female ratio in the non-cirrhotic group was 1.5:1, very different to the 8.8:1 in the cirrhotic group. Cirrhosis was associated with excessive alcohol consumption in 92% of cases. The prevalence of serological markers of hepatitis B virus infection was investigated in 91 patients. Hepatitis Bs-antigen was found in 8.8% and evidence of past or present infection in 28.2%. In view of the prevalence of chronic alcoholism in patients with cirrhosis it is suggested that alcohol leads to an increased risk of cirrhosis followed by an increased incidence of PLC. Further studies are needed to elucidate the eventual role of HBV infection and other suspected environmental factors in the aetiology of PLC.

Occupational cancer risk associated with the storage and bulk handling of agricultural foodstuff.

The cancer mortality experience of 2649 Swedish grain millers was followed during the period from 1961 to 1979. Although the overall cancer incidence was not elevated, the risk of primary liver cancer was significantly elevated for this group (standard incidence ratio = 238). The Swedish data is compared to the cancer mortality experience of workers in the Netherlands and the United States who are also involved in the bulk handling and storage of agricultural foodstuffs (e.g., peanuts, grains). The varying occupational exposures in this international comparison help establish etiologic hypotheses in the absence of comprehensive exposure information. Agents of potential concern include metabolic products of fungal contaminants (e.g., aflatoxins) and pesticides used to protect grain from insect infestation.

Risk of cirrhosis and primary liver cancer in alpha 1-antitrypsin deficiency.

Previous reports have suggested an association between homozygous alpha 1-antitrypsin deficiency, cirrhosis, and primary liver cancer. To assess the risk of these complications we conducted a retrospective study based on 17 autopsied cases of alpha 1-antitrypsin deficiency identified during the period 1963 to 1982 in the city of Malmö, Sweden. During the study period, autopsies were performed in 38,250, or 68.2 percent, of all patients in the city who died. From the homozygote frequency in the population, 21 of these were expected to have alpha 1-antitrypsin deficiency. The disease had been diagnosed in 20, and autopsies had been performed in 17 (1 child and 16 adults). Each autopsied case was matched with four controls selected from the same autopsy register, and the Mantel-Haenszel odds ratio (ORmh) was calculated. The results indicated a strong relation between alpha 1-antitrypsin deficiency and cirrhosis (ORmh = 7.8; 95 percent confidence limits, 2.4 to 24.7) and primary liver cancer (ORmh = 20; 95 percent confidence limits, 3.5 to 114.3). When data were stratified according to sex, these associations were statistically significant only for male patients. We conclude that men with alpha 1-antitrypsin deficiency may be at higher risk for cirrhosis and primary liver cancer. The apparent male predominance suggests the additive effects of exogenous factors.

A Case-Control Dietary Study of Primary Liver Cancer Risk from Aflatoxin Exposure*

The dietary intakes of 90 confirmed primary liver cancer cases were compared against 90 age-sex matched controls. Dietary recall, obtained by the same nutritionist, was taken for each change of residence lasting one year or more. The frequency and amounts of food items consumed were calculated into units of aflatoxin load per day using a Philippine table of aflatoxin values of these items. Of the total subjects' aflatoxin load, 51.2% came from cassava, 20.3% from corn, 6.8% from peanuts and 5.8% from sweet potato. The mean aflatoxin load per day of the cases as found to be 440% that of the controls. Upon grouping dietary aflatoxin loads (and alcohol intakes) into Heavy and Light, and upon comparing cases versus controls, the relative risk (RR) of developing primary liver cancer was found to be statistically significant in the following order of rank: cassava, peanuts, sweet potato, corn and alcohol. Boiled rice which had negligible aflatoxin content gave no difference in risk. Combining aflatoxin load and alcohol intake gave a synergistic and a statistically significant effect on RR with Light Aflatoxin, Light Alcohol as RR = 1. Light Aflatoxin, Heavy Alcohol RR = 3.9; Heavy Aflatoxin, Light Alcohol RR = 17.5; Heavy Aflatoxin, Heavy Alcohol RR = 35.0.