Smoking as a risk factor in hepatocellular carcinoma. A case-control study in southern African blacks

Two hundred forty southern African black patients with hepatocellular carcinoma and control subjects matched for race, sex, age, and urban or rural background were questioned about their smoking habits. Patients with hepatocellular carcinoma were not more likely to smoke or to smoke heavily than the control subjects. This was also true of the subgroups: men and women, and urban and rural background. There was a slightly increased relative risk associated with smoking in all patients who showed no serum markers of current or past hepatitis-B virus infection and in patients older than 50 years who did not have markers of current or past hepatitis-B virus infection. However, this was not statistically significant, and was not supported by a linear trend, the risk in heavy smokers being less than 1. Rural black patients, who have a higher incidence of hepatocellular carcinoma than urban black patients, smoked less than their urban counterparts. We conclude that smoking is not an unqualified risk factor for hepatocellular carcinoma in southern African black patients. There may, however, be a trend toward smoking playing an etiologic role in patients without hepatitis-B virus infection, especially in older patients.     

Alpha-L-fucosidase as a serum marker of hepatocellular carcinoma in southern African blacks

The purpose of this study was to compare alpha-L-fucosidase and alpha-fetoprotein as serum markers of hepatocellular carcinoma in 72 southern African blacks with this tumour and 64 matched patients with benign hepatic diseases which might be mistaken clinically for hepatocellular carcinoma. Alpha-L-fucosidase activity was assayed using p-nitrophenyl-L-fucopyranoside (pNpf) as a substrate and alpha-fetoprotein concentrations were measured by radioimmunoassay. Serum alpha-L-fucosidase activity in the patients with hepatocellular carcinoma (mean 1,268, s.e.m. +/- 83.7, median 1,150 and range 38-3,698 nmol pNpf ml-1 h-1) was significantly higher than that in the matched controls (mean 798, s.e.m. +/- 65.8, median 648 and range 273-3,825 nmol pNpf ml-1 h-1) (P = 0.0001). However, alpha-L-fucosidase was both less sensitive (75 versus 87%) and less specific (70 versus 87%) than alpha-fetoprotein as a serum marker of hepatocellular carcinoma. When, in an endeavour to eliminate false-positive results, the diagnostic cut-off level for alpha-L-fucosidase was increased to 1,500 nmol pNpf ml-1 h-1 and for alpha-fetoprotein to 400 ng ml-1, the sensitivity of alpha-L-fucosidase fell to 21% whereas that of alpha-fetoprotein remained satisfactory at 78%. If the two markers were used together, the number of false-negative alpha-fetoprotein results was reduced from 13 to 5.5%. We conclude that alpha-L-fucosidase is less useful than alpha-fetoprotein as a single marker of hepatocellular carcinoma in southern African blacks. However, the two markers can profitably be used together.     

The prevalence of variant alkaline phosphatase in hepatocellular carcinoma in southern African blacks

The prevalence of variant alkaline phosphatase in the serum of 335 southern African blacks with hepatocellular carcinoma was determined using polyacrylamide gel electrophoresis. The isoenzyme was detected in 2% (seven of 335) of the patients: it could not be found in the serum of 300 matched, healthy individuals or in 56 patients with various benign hepatic diseases. Variant alkaline phosphatase is thus of little use as a diagnostic marker of hepatocellular carcinoma in southern African blacks. The reported prevalence of this isoenzyme in hepatocellular carcinoma ranges between 3% and 31%. Higher frequencies usually are recorded in populations with a low incidence of the tumor, and the lowest frequencies have been found in Chinese patients. Our finding of variant alkaline phosphatase in only 2% of another high incidence population fits this trend. Patients with tumors that secreted the variant isoenzyme had a significantly higher serum total alkaline phosphatase activity than those with tumors lacking this property.     

Hepatitis B virus infection in southern African blacks with hepatocellular cancer.

The association between hepatitis B virus (HBV) infection and hepatocellular cancer (HCC) in southern African blacks was investigated by examination of patients' sera for all the currently known markers of HBV. Hepatitis B surface antigen (HBsAg) was present in the sera of 61.6% (178/289) of the patients compared with only 11.3% (24/213) of age-matched, sex-matched, and ethnically matched controls (P less than 0.001). Antibody against HBsAg was found in 17% of the patients and 41.7% of the controls (P less than 0.001). In 74 patients studied in more detail, antibody against the hepatitis B core antigen (anti-HBc) was detected in 89%, almost always in high or moderately high titer. Anti-HBc was found in 37.5% of the controls. Active HBV infection, as indicated by positive tests for HBsAg or anti-HBc, was present in 91% of the patients compared with 39.4% of the controls (P less than 0.001). Hepatitis B e-antigen was detected in 2.3% and its specific antibody in 20.5% of the patients. The corresponding figures in the controls were 0 and 55%. HBs antigenemia was more common in younger patients with HCC. No relationship was demonstrated between alpha-fetoprotein and HBs antigenemia. HBV infection was equally common in patients with and without cirrhosis in the nontumorous liver.     

Alcohol as a primary risk factor in oral squamous carcinoma

This case-control study investigates the role of alcohol as a primary risk factor in the development of oral cancer. A total of 181 patients diagnosed as having squamous carcinoma of the oral cavity were interviewed, and 497 controls. The relative risk for drinkers adjusted for smoking was 3.3, 15.2, and 10.6 for those who drank less than six, six to nine, and 10 or more whiskey equivalents (WEs) a day, respectively. The relative risk for smokers adjusted for drinking rose only from 3.2 to 4.5 to 5.0 for smokers of 10 to 19, 20 to 39, and 40 or more cigarettes a day, respectively. Beer/wine drinkers had much higher relative risks than the whiskey drinkers. The adjusted relative risk for whiskey drinkers consuming 10 or more WEs a day was 7.3; the adjusted relative risk for beer/wine drinkers consuming 10 or more WEs a day was 20.4. These results indicate that drinkers of six or more WEs a day may be at greater risk than smokers of 40 or more cigarettes a day, and that beer and wine may be greater risk factors than whiskey in the development of oral cancer.     

Serum vitamin B12 binders in South African blacks with hepatocellular carcinoma

Sera from 242 South African blacks with hepatocellular carcinoma were assayed for unsaturated vitamin B12 binding capacity (UBBC) and vitamin B12 activity. Six patients were younger than 20 years of age, and 24% were younger than 30 years of age. Eighty-four percent of the patients had a slightly raised UBBC and 86% had a slightly elevated vitamin B12 value, but in no patient was an exceptionally high UBBC present. Serum UBBC and vitamin B12 were not higher in younger patients, and raised UBBC values were not related to serum alpha-fetoprotein values. Serum UBBC and vitamin B12 concentrations were not significantly different in patients with and without coexisting cirrhosis. In none of the patients with a UBBC above 3000 pg/ml was the fibrolamellar variant of hepatocellular carcinoma present. The authors conclude that South African blacks with hepatocellular carcinoma do not secrete an abnormal vitamin B12 binding protein.     

Betel quid chewing as a risk factor for hepatocellular carcinoma: a case-control study

The role of betel quid chewing in the aetiology of hepatocellular carcinoma (HCC) was evaluated in a case-control study including 263 pairs of age- and sex-matched HCC patients and healthy controls. Serum hepatitis B surface antigen (HBsAg), and antibodies to hepatitis C virus (anti-HCV) were determined, and standardized personal interview conducted using a structured questionnaire. Multivariate analysis indicated that betel quid chewing (odds ratio (OR), 3.49; 95% confidence interval (CI), 1.74-6.96), HBsAg (OR, 16.69; 95% CI, 9.92-28.07), anti-HCV (OR, 38.57; 95% CI, 18.15-81.96), and educational duration of less than 10 years (OR, 1.71; 95% CI, 1.05-2.78) are independent risk factors of HCC. In addition, there was an additive interaction between betel quid chewing and chronic infection with either hepatitis B virus (synergy index, 5.37) or hepatitis C virus (synergy index, 1.66). Moreover, risk on HCC increased as duration of betel quid chewing increased, or amount of betel quid consumed (each P for trend < 0.0001).     

Alcohol injection: a treatment for ruptured hepatocellular carcinoma.

Nine patients with bleeding from a ruptured hepatocellular carcinoma had absolute alcohol injection. Laparotomy and alcohol injection stopped the bleeding in seven patients. Injection under laparoscopic visualization was attempted in two patients and in one patient haemostatis was achieved initially. He rebled, however, 4 h later and laparotomy failed to control the bleeding. He died 2 days later because of coagulopathy and renal failure. In the second patient, bleeding was not controlled laparoscopically and immediate laparotomy and alcohol injection stopped the bleeding. The eight patients who survived left hospital between 8 and 21 days after surgery (median 10 days). In our experience, laparotomy and alcohol injection achieved good results in bleeding hepatocellular carcinoma.     

Cancer survival in a southern African urban population

This paper provides the first comprehensive population based cancer survival estimates from the African continent. Five-year absolute and relative survival estimates are presented for black and white Zimbabwean patients diagnosed with cancer in Harare, Zimbabwe between the years 1993 and 1997. The survival of black Zimbabwean cancer patients are among the lowest ever reported from population based cancer registries. For most cancer sites, white Zimbabwean patients have much higher survival than black Zimbabweans, except for lung and colorectal cancer, for which the estimates are similarly poor. Race specific comparisons to cancer patients in the United States show that Zimbabwean patients have much lower survival than American cancer patients and that the gap between black Zimbabwean patients and black American patients is broader than between white Zimbabwean and white American patients. Access to and the ability to pay for medical care may be a very important barrier to better survival for the majority of black Zimbabwean patients and the most important cause for the very low cancer survival in this population.     

Lymphocyte-to-C-reactive protein ratio as a prognostic factor for hepatocellular carcinoma

International Journal of Clinical Oncology - Systemic inflammation has been correlated with worse survival for some cancers. We evaluated prognostic values of various inflammatory factor...     

Past exposure to hepatitis B virus as a risk factor for hepatocellular carcinoma in patients with chronic liver disease.

The aim of the study was to determine whether past exposure to hepatitis B virus (HBV) influences the risk of the development of hepatocellular carcinoma (HCC) in Japanese patients with chronic liver disease (CLD). We conducted a hospital-based case-control study of 141 HCC patients with CLD and 151 controls with CLD but without HCC. Past exposure to HBV was assessed by antibody to hepatitis B core antigen (anti-HBc) positivity. Ninety-two patients (65%) with HCC were anti-HBc positive compared with 65 patients (43%) with CLD alone (P < 0.01). A multivariate analysis using logistic regression modelling revealed that anti-HBc positivity significantly increased the risk of the development of HCC [odds ratio (OR) 2.0, P = 0.01]. In the anti-HBc-positive patients, a significantly increased risk of HCC was seen among the patients positive for anti-HBc alone (OR, 2.6; P < 0.01). However, a significant OR was not obtained among the patients with a transient HBV infection implied by positivity for both antibody to hepatitis B surface antigen and anti-HBc (OR, 1.5; P = 0.48). These results indicate that past exposure to HBV is a risk factor for HCC in Japanese CLD patients, especially when they have no serological evidence of immunity to HBV.     

A population-based study of hepatitis D virus as potential risk factor for hepatocellular carcinoma

Hepatitis D virus (HDV) is dependent on the presence of hepatitis B virus (HBV) for transmission and replication because of its inability to produce its own coat. It remains unclear whether HDV infection increases the risk of hepatocellular carcinoma. Using the Swedish Hospital Discharge Register and Outpatient Registry, we identified 9160 patients with chronic HBV infection between 1997 and 2008, of whom 327 had chronic HDV infection and 323 had acute HDV infection. Standardized incidence ratios (SIRs) were calculated for these patients compared with the general population. The risk of hepatocellular carcinoma was greatly increased in patients with HBV and HDV (SIR = 137.17, 95% confidence interval [CI] = 62.19 to 261.51). The risk of hepatocellular carcinoma among patients with HBV and HDV was increased (SIR = 6.11, 95% CI = 2.77 to 11.65) when patients with chronic HBV infection alone were used as the reference population. Similar results were observed for patients with chronic HDV infection (SIR = 99.26, 95% CI = 42.39 to 196.55). Our findings indicate that HDV is a strong risk factor for hepatocellular carcinoma.     

饮酒与膀胱癌关系的全人群病例对照研究

目的探讨饮酒与膀胱癌发生的关系。方法采用全人群为基础的病例对照研究,共调查1996年1月1日~1998年12月31日期间确诊的上海市区膀胱癌新发病例608例,健康人群对照607例。采用非条件logistic回归分析,调整吸烟等可能的混杂因素,以估计饮酒对膀胱癌发生的危险度及其95%可信区间。结果与不饮酒者相比,男、女性饮酒者患膀胱癌相对危险度分别是1.22(95%CI0.94~1.59)、0.50(95%CI0.13~1.90)。男性随总酒精摄入量增加患膀胱癌的危险有增加趋势,OR值分别为1.10(1~80g/d)和1.56(>80g/d)(趋势检验P=0.043)。男性总酒精摄入量与饮酒年限的联合作用分析表明,与不饮酒者相比,总酒精摄入量超过80g/d、饮酒年限超过40年者患膀胱癌危险度为2.11(95%CI1.11~4.01)。将饮酒分3层、吸烟分4层进行男性饮酒与吸烟的联合作用分析,结果显示总酒精摄入量>80g/d且吸烟≥35包年者的OR值为2.78(95%CI1.46~5.28)。未发现各饮酒种类与男性膀胱癌有显著关联。在不吸烟男性组中的分析显示,饮酒习惯的OR值均没有统计学意义。结论饮酒可能与男性膀胱癌有一定联系,但作用较弱,似乎主要表现为对吸烟男性的作用。     

Serum thyroglobulin as a risk factor for thyroid carcinoma

Samples from a biological serum bank taken up to 23 years prior to diagnosis of thyroid carcinoma were analysed for human thyroglobulin, thyroid-stimulating hormone and thyroxin. After exclusions, the final study material consisted of 59 cases of papillary and follicular carcinomas. These cases were compared with 164 controls, matched for sex, age and time of sample taking. The most interesting finding was that concentrations of thyroglobulin in serum were abnormally elevated in cases compared with controls, equal to or above 30 microg/L, with odds ratio 7.0 (CI 3.1-15.7). This elevation of serum thyroglobulin occurred in 44% of the carcinoma cases. Sensitivity was around 50 for measurements taken up to 15 years prior to diagnosis, but 21 when the interval was over 15 years. Specificity was 89. No differences were found between cases and controls in values for thyroid-stimulating hormone and thyroxin.     

Coffee and tea consumption and risk of hepatocellular carcinoma in Italy

The role of coffee in the aetiology of hepatocellular carcinoma has raised great interest. In Italy, coffee consumption is high, thus allowing the investigation of the topic over a broad range of consumption. A hospital-based case-control study was conducted in Italy in 1999-2002, including 185 incidents, histologically confirmed cases of hepatocellular carcinoma aged 43-84 years. Controls were 412 subjects admitted to the same hospitals' networks for acute, non-neoplastic diseases unrelated to diet. Coffee and tea consumption were assessed using a validated food-frequency questionnaire. Odds ratios (ORs) and corresponding the 95% confidence intervals (CI) were computed using unconditional multiple logistic regression, adjusting for hepatitis viruses seropositivity, alcohol intake, smoking habits and other potential confounding factors. Compared to people who drunk <14 cups/week of coffee, the risk of hepatocellular carcinoma decreased for increasing levels of consumption (OR=0.4, 95% CI: 0.2-1.1 for >or=28 cups/week, p for trend = 0.02). In the present study, inverse relations were observed across strata of hepatitis C and, B virus infections and alcohol drinking. No significant association emerged with consumption of decaffeinated coffee (OR=0.7, 95% CI=0.2-2.5) or tea (OR=1.4, 95% CI=0.8-2.7). The present study supports the hypothesis of a favourable effect of coffee, though not decaffeinated coffee and tea, on the risk on hepatocellular carcinoma.     

Smoking as an independent risk factor for hepatocellular carcinoma: the Singapore Chinese Health Study

Background:

Given the close correlation between smoking and alcohol intake in most epidemiologic studies, it is difficult to exclude the residual confounding effect of alcohol in the association between smoking and hepatocellular carcinoma (HCC).

Method:

We evaluated the association between smoking and risk of HCC in the Singapore Chinese Health Study, a prospective cohort with a low prevalence of alcohol intake. Information on cigarette smoking and alcohol consumption was obtained through in-person interviews conducted at enrolment.

Results:

After a mean of 11.5 years of follow-up, there were 394 incident cases of HCC. Participants who consumed more than two alcoholic drinks per day showed an increased risk for HCC (hazard ratio (HR)=2.24; 95% confidence interval (CI)=1.46–3.41). After adjusting for alcohol consumption and other potential confounders, current vs never smokers had a statistically significant, increased risk of HCC (HR=1.63; 95% CI=1.27–2.10) that was dose-dependent (number of cigarettes per day, P for trend<0.001). The observed tobacco–HCC association also was duration-dependent (years of smoking in ever smokers, P for trend=0.002). When we excluded daily drinkers from the analysis, all risk estimates remained essentially the same and statistically significant.

Conclusion:

Our findings strongly implicate tobacco smoke as a causal factor of HCC development.     

Expression of CD147 as a significantly unfavorable prognostic factor in hepatocellular carcinoma.

The aim of this study is to investigate whether the expression of CD147 could be a prognostic factor for hepatocellular carcinoma. Tissue samples from 111 hepatocellular carcinoma patients were immunohistochemically stained with anti-CD147, anti-matrix metalloproteinases-2 and anti-vascular endothelial growth factor antibodies. Tumor microvessel density was evaluated using CD34. The survival curves were estimated by Kaplan-Meier analysis and the prognostic significance of the marker was analyzed using the log-rank test. In addition, the identification of relevant prognostic factors was performed by multivariate Cox regression analysis. CD147 was mainly expressed in cancerous lesions and its expression was positively correlated with metalloproteinases-2 (P<0.0001), vascular endothelial growth factor (P<0.0001) and microvessel density CD34 (P<0.0001). Furthermore, CD147 was significantly associated with the presence of venous invasion (P=0.0013), tumor size (P<0.0001) and pTNM tumor stages (P=0.0001), as well as serum alpha-fetoprotein level (P<0.0001). Patients with positive expression of CD147 had poorer tumor recurrence-free survival than those with negative expression of CD147 (P<0.0001). Analyzed by a proportional hazard model, strong expression of CD147 had the highest risk ratio of recurrence among these markers (P<0.0001). The findings suggest that CD147 may be a significant independent predictor of poor survival in patients with hepatocellular carcinoma, and may be involved in tumor growth, invasion and angiogenesis in hepatocellular carcinoma.     

Increased serum ferritin in chronic liver disease: a risk factor for primary hepatocellular carcinoma

Previous studies from this laboratory support the view that increased serum ferritin levels are associated with an increased risk of primary hepatocellular carcinoma (PHC). We have tested this hypothesis in a population of Korean patients with chronic liver disease followed for development of PHC. Serum ferritin levels were measured over time in 249 patients with liver diseases (mostly chronic) followed for 2 to 17 years in Seoul, Korea. Most of the patients were chronically infected with hepatitis B virus. During the first 8 months of follow-up, there were no cases of PHC and no deaths. During this same period, no patient had a serum ferritin level initially below 300 ng/ml and rising above 300 ng/ml, but some patients with ferritin levels above 300 ng/ml experienced decreases to below 300 ng/ml. Therefore, patients were grouped by ferritin level during the first 8 months of follow-up into 3 categories according to the above criteria. Multivariate analysis showed that consistently elevated ferritin levels (category 3) were significantly associated with the development of PHC. Men were more likely to have elevated ferritin levels than women and were at higher risk of developing PHC. Men who were chronically infected with HBV and had ferritin levels above 300 ng/ml had a 50% chance of developing PHC during the follow-up period, compared with a 20% risk of PHC for men with lower ferritin levels (categories 1 and 2). This elevated risk of PHC in men with elevated ferritin levels was confined to the first 3 years of follow-up.     

Alcohol consumption in a case-control study of breast cancer in southern France

The effect of alcohol consumption on breast cancer risk was investigated in a hospital-based, case-control study of 808 patients (349 cases and 459 controls) in Montpellier (France). Semi-quantified diet history including beverage consumption as well as relevant medical and personal characteristics were assessed by interview. A dose-rate relationship for total alcohol consumption was found with unadjusted odds ratios ranging from 1.8 (95% CI 1.2-2.8) for 1 to 2 drinks per week to 3.5 (95% CI 2.0-6.1) for more than 17 drinks per week, in comparison with less than 1 drink per week. Confounding by known or suspected determinants of breast cancer, smoking, use of oral contraceptives, lipid and vitamin consumption was looked into. Significant interactions were found with level of education and lipid consumption, with a higher risk for alcohol in women having had less schooling or consuming less fat. Adjustment with respect to the other risk factors did not modify the relationship. There was a significant risk increase both for wine and stronger drinks. Along with several other studies, our results give support to the hypothesis that alcohol is a risk factor in breast carcinogenesis.