A case-control study of hepatocellular carcinoma and the hepatitis B virus, cigarette smoking, and alcohol consumption

A case-control study was undertaken to evaluate the roles of the hepatitis B virus (HBV), cigarette smoking, and alcohol use in the etiology of hepatocellular carcinoma (HCC). A major purpose of the study was to evaluate the effect of cigarette smoking on HCC among hepatitis B surface antigen (HBsAg)-negative persons, since it had been suggested that the relative effect of cigarette smoking on HCC was higher among HBsAg-negative persons than among HBsAg-positive persons. Eighty-six cases and 161 hospital controls were included in the study. This study confirmed the strong relationship between the HBV and HCC. Twelve of 67 cases and none of 63 controls were chronically infected with HBV as evidenced by serum HBsAg. The study also found a moderately strong relationship between alcohol use and HCC. The results of the present study do not support the hypothesis that cigarette smoking is a risk factor for HCC. Among all subjects, the relative rate of HCC for cigarette smokers compared with nonsmokers after adjustment for alcohol consumption was 1.0 with 95% confidence limits, 0.5 to 1.8. Among HBsAg-negative subjects, the relative rate was 1.1 with 95% confidence limits, 0.5 to 2.4. There was also no consistent dose-response relationship between quantity smoked and HCC in this study.     

Hepatitis B virus, cigarette smoking and alcohol consumption in the development of hepatocellular carcinoma: a case-control study in Fukuoka, Japan.

The roles of the hepatitis B virus (HBV), cigarette smoking and alcohol consumption in the etiology of hepatocellular carcinoma (HCC) were examined in a case-control study involving 204 patients with HCC and 410 control subjects in Fukuoka prefecture, where HCC risk is among the highest in Japan. Information on smoking and drinking habits was obtained by a detailed interview survey, and the results were analyzed in conjunction with serum hepatitis B surface antigen (HBsAg) status after adjustment for sex, age and other possible confounding factors. Individuals positive for serum HBsAg showed a relative risk (RR) for HCC of 13.8 (95% confidence interval, Cl 5.9 to 32.5), whereas heavy drinkers experienced about a 2-fold risk increase compared with non-drinkers. Light or moderate drinkers, however, demonstrated RRs near the unity. Some risk excess was observed among ex-smokers (RR = 1.5, 95% CI 0.8 to 2.8) and current smokers (RR = 1.5, 0.8 to 2.7) compared with non-smokers, but without evidence for a dose-response relationship in terms of pack-years. Analysis among HBsAg-negative subjects revealed similar non-significant association with smoking, and there was no clear interaction between alcohol and cigarette consumption on HCC risk. Other significant risk factors included positive histories of blood transfusion (RR = 3.7, 2.2 to 6.3) and familiar liver disease (RR = 2.6, 1.6 to 4.2). Attributable risk calculations suggest that chronic HBV infection and heavy drinking may account for 17% and 13% of HCC occurrence, respectively, in this high risk area. The association of cigarette smoking with HCC was not evident in our study.     

Blood transfusion, alcohol consumption, and cigarette smoking in causation of hepatocellular carcinoma: a case-control study in Fukuoka, Japan

In the present study, we investigated the association between hepatocellular carcinoma (HCC) and hepatitis B virus infection (HBV), blood transfusion and drinking and smoking habits by comparing 124 HCC cases and 250 controls. We confirmed a very high relative risk (RR), i.e. 31.0 (P less than 0.001), among persons who were positive for serum hepatitis B surface antigen (HBsAg). However, the prevalence of serum HBsAg positives among our cases was only 21%, about half of those reported earlier, indicating a role of other etiological factors. Those who have a history of blood transfusion showed a significantly elevated RR of 3.0 (P less than 0.001) or 4.9 (P less than 0.001), and most of them (85%) were non-carriers of HBV. Thus, the past history of blood transfusion is an important risk factor among the Japanese. Unidentified non-A, non-B hepatitis viruses in transfused blood probably play a significant role in causing HCC. We estimated that 15% of male HCCs were attributable to blood transfusion. A positive relationship between alcohol consumption and HCC was detected, particularly among HBsAg-negative subjects with no history of blood transfusion who had drunk heavily in their younger years. RR estimates were not great (e.g., heavy drinkers: 2.5), but a substantial proportion of HCC may be attributed to drinking because of common drinking habits among Japanese males. Smoking was also found to have a positive association, but the relationship at a young age was less clear, and further investigation is needed to clarify the etiological role of smoking.     

吸烟、饮酒与胃癌关系的病例对照研究

目的 探讨吸烟、饮酒与胃癌发生的关系。方法 采用全人群病例对照研究,共调查1999年4月－1999年10月期间诊断的上海市区新发胃癌病例311例,对照1579例（注：本课题为“九五”中乳腺癌、肺癌及胃癌病例－对照之一,对照共用）。采用非条件logistic回归分析,调整可能的混杂因素,以估计吸烟、饮酒对胃癌发生的比数比和95％的可信区间。结果 吸烟与男性胃癌发生有关,调整OR为1．67（95％CI：1．14－2．460,并且随着吸烟年龄的提前（P＜0．01）、吸烟年限的延长（P＜0．05）、每日吸烟量的增加（P＜0．05）和吸烟包－年（P＜0．01）,患胃癌的危险性显著增大;未发现女性吸烟与胃癌发生有显著性联系。进一步调整整烟,发现饮酒与胃癌无密切关系,但重度饮酒可能与女性胃癌发生有关。进一步研究饮酒的作用,分析吸烟与饮酒状况及吸烟支数与酒精克数不同剂量分层之间的交互作用,调整年龄、文化程度（仅女性）、腌制食品、新鲜水果及慢性胃炎后,发现男性饮酒与吸烟不同剂量之间有交互作用存在,交互项χ^2值为5．20,P＝0．02,即饮酒增加男性吸烟者患癌的危险。结论 进一步证实吸烟是胃癌发生的危险因素;单独饮酒与胃癌发生无明显关系,饮酒不是胃癌的一项独立危险因素;饮酒增加吸烟患胃癌的危险,两者有协同作用。     

A case-control study of hepatitis B and C virus infections in the etiology of hepatocellular carcinoma

During a 16-month period in 1991-1992, blood samples and questionnaire data were obtained from 65 incident cases of hepatocellular carcinoma (HCC) as well as from 2 control groups of hospitalized patients matched on gender and age, which included 65 metastatic liver cancer (MLC) patients and 65 patients hospitalized for eye, ear, nose or throat conditions. Coded sera were tested for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen, antibody to HBsAg and antibody to hepatitis C virus (anti-HCV) by enzyme immunoassay. The odds ratios (with 95% confidence intervals) in logistic regression modeling comparing the HCC cases to the combined control series were 18.8 (8.2–43.2) for the presence of HBsAg and 7.7 (1.7–35.1) for anti-HCV. In the present hospital-based case-control study anti-HCV testing was conducted on recently collected sera, using a second-generation enzyme immunoassay with confirmation by immunoblot assay. Comparisons with previous work in a similar population demonstrated that, when second-generation anti-HCV assays are applied to sera stored for 7–15 years, confirmatory assays or a higher diagnostic cut-off point may be necessary to ensure that the testing is specific.     

重度饮酒与HBV相关肝癌危险性的关系

目的了解饮酒与乙型肝炎病毒(hepatitisBvirus,HBV)感染在肝细胞癌(hepatocellularcarcinogenesis,HCC)发生中的相互作用。方法采用病例对照研究方法,在江苏省淮安市以219例HCC患者为病例组,219例非HCC的上消化道恶性肿瘤患者,如胃癌、胆囊癌及胰腺癌等为对照组。通过问卷调查采集HCC危险因素信息,用ELISA法测定血标本中乙型肝炎病毒表面抗原(hepatitisBsurfaceantigen,HBsAg),并应用非条件Logistic回归模型计算比数比(oddsratio,OR)和95%可信区间(confidenceinterval,CI)。结果HBsAg阳性、轻度饮酒和重度饮酒(≥80mL/d乙醇)的多变量OR及其95%CI分别为28.2(10.6～75.5)、2.2(0.9～4.9)和1.2(0.5～3.1),轻度饮酒HBsAg阳性的多变量OR及其95%CI为28.6(11.7～70.2),而重度饮酒和HBsAg阳性的协同OR为50.3(19.2～131.6)。结论HBV感染是淮安市HCC的重要危险因素。饮酒虽然不是HCC的独立危险因素,但重度饮酒可增加罹患HBV相关HCC的危险性。     

Hepatitis B virus, tobacco smoking and ethanol consumption in the etiology of hepatocellular carcinoma

Tobacco smoking and alcohol drinking histories were obtained from 194 patients with hepatocellular carcinoma (HCC) and 456 hospital controls, and the results were analysed in conjunction with the results of serological determinations of hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs) and antibody to hepatitis B core antigen (anti-HBc) in all subjects, as well as the presence or absence of cirrhosis in HCC patients. The relative risk (RR) of HCC (and 95% confidence interval) among HBsAg-positive subjects was 13.7 (8.0-23.5), whereas the excess risk among antibody-positive subjects was small and statistically non-significant. In the presence of cirrhosis the RR for HBsAg-positive subjects was considerably higher (30.7 vs. 7.1 among HBsAg-positive subjects without cirrhosis) indicating that HBV may affect the development of HCC through at least two different and potentially multiplicative mechanisms (DNA integration and liver regeneration). Moderate ethanol consumption does not affect the risk of HCC, but there is a statistically significant and dose-dependent association between tobacco smoking and HBsAg-negative HCC. In most of the developed countries of Europe and North America, where the prevalence of HBsAg carrier state is very low and tobacco smoking very common, more cases of HCC may be due to tobacco smoking than to HBV, even though the RR for HCC is much higher among HBsAg carriers than among tobacco smokers.     

Tobacco smoking,alcohol consumption and pancreatic cancer risk: A case-control study in Italy

In Italy, pancreatic cancer accounts for approximately 5% of cancer-related deaths. Tobacco smoking is the major established risk factor for this cancer, whereas the role of alcohol consumption is open to debate.Between 1991 and 2008, we conducted a hospital-based case-control study on pancreatic cancer in northern Italy. Cases were 326 patients (median age 63 years) with incident pancreatic cancer admitted to major general hospitals. Controls were 652 patients (median age 63 years) with acute non-neoplastic conditions admitted to the same hospital network of cases. Multiple logistic regression was used to estimate the odds ratios (OR) and the corresponding 95% confidence intervals (CI).Pancreatic cancer was associated to current smoking (OR = 1.68; 95% CI: 1.13–2.48), and the risk rose with increasing number of cigarettes/day (OR = 2.04; 95% CI: 1.14–3.66 for ?20 cigarettes/day). No association emerged for former smokers (OR = 0.98; 95% CI: 0.66–1.45). Alcohol consumption was associated to increased pancreatic cancer risk, but ORs were significant only among heavy drinkers (ORs: 2.03 and 3.42 for 21–34 and ?35 drinks/week, respectively). Pancreatic cancer risk was 4.3-fold higher in heavy smokers (?20 cigarettes/day) and heavy drinkers (?21 drinks/week) in comparison with never smokers who drunk <7 drinks/week, which is compatible with an additive effect of these exposures.In conclusion, we found that tobacco smoking and alcohol drinking are two independent risk factors for pancreatic cancer which may be responsible for approximately one third of these cancers in our population.     

Hepatitis B virus and cigarette smoking: risk factors for hepatocellular carcinoma in Hong Kong

One hundred seven Chinese patients with primary hepatocellular carcinoma (PHC) were compared with 107 hospital controls for the presence of hepatitis B surface antigen and smoking, drinking, and dietary habits. Eighty-two % of PHC cases were hepatitis B surface antigen positive compared to 18% of controls (relative risk, 21.3; 95% confidence limits, 10.1 and 45.9). Prior history of jaundice was significantly related to PHC, independent of hepatitis B surface antigen status. There was a significant association between cigarette smoking and PHC negative for hepatitis B surface antigen. The relative risk of hepatitis B surface antigen-negative PHC for heavy smokers (20 + cigarettes/day) was 3.3 compared to light smokers and nonsmokers (95% confidence limits, 1.0 and 13.4). Our data indicated that infection by the hepatitis B virus and cigarette smoking were independent risk factors for PHC.     

The effect of interaction between hepatitis C virus and cigarette smoking on the risk of hepatocellular carcinoma

We evaluated the interaction between hepatitis C virus (HCV) and cigarette smoking on death from hepatocellular cancer in The Japan Collaborative Cohort Study. The odds ratio of death from HCC for smoking was 9.60 (1.50-61.35) and 1.71(0.58-5.08) among anti-HCV positive and negative individuals, respectively.     

Tobacco smoking, alcohol consumption and their interaction in the causation of hepatocellular carcinoma

During a 4-year period from January 1995 to December 1998, blood samples and questionnaire data were obtained from 333 incident cases of hepatocellular carcinoma (HCC), as well as from 360 controls who were hospitalized for eye, ear, nose, throat or orthopedic conditions in Athens, Greece. Coded sera were tested for hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV) by third-generation enzyme immunoassays, and information on smoking habits and beverage consumption was obtained. We found a significant dose-response, positive association between smoking and HCC risk [>/= 2 packs per day, odds ratio (OR)=2.5].This association was stronger in individuals without chronic infection with either HBV or HCV (>/= 2 packs per day, OR=2.8). Consumption of alcoholic beverages above a threshold of 40 glasses per week increased the risk of HCC (OR=1.9). We also found evidence of a strong, statistically significant and apparently super-multiplicative effect of heavy smoking and heavy drinking in the development of HCC (OR for both exposures=9.6). This interaction was particularly evident among individuals without either HBsAg or anti-HCV (OR for both exposures=10.9). Coffee intake was not positively associated with HCC risk, but the reverse could not be excluded for the subgroup of chronically infected individuals. In conclusion, tobacco smoking and heavy alcohol consumption are associated with increased risk of HCC, especially when these 2 exposures occur together.     

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.     

N-Acetyltransferase-2, glutathione S-transferase M1 and T1 genetic polymorphisms, cigarette smoking and hepatocellular carcinoma: a case-control study

Our aim was to evaluate the role of N-acetyltransferase (NAT2) and glutathione S-transferase M1 and T1 (GSTM1 and GSTT1) polymorphisms in hepatocellular carcinoma (HCC) according to cigarette smoking, taking into account hepatitis B (HBV) and C (HCV) viral infection as well as alcohol consumption. A hospital-based case-control study was conducted in 2 areas of north Italy. Cases (n = 200) were patients hospitalized for HCC, and controls (n = 400) were patients admitted for reasons other than liver disease, neoplasms and tobacco- and alcohol-related diseases. Genotypes were determined using PCR and the PCR/restriction fragment length polymorphism-based method. The putative risk genotypes NAT2 slow acetylator, GSTM1 null and GSTT1 null were not associated with HCC (OR = 1.3, 95% CI 0.8-2.0; OR = 1.0, 95% CI 0.6-1.5; OR = 0.8, 95% CI 0.4-1.4, respectively). Although not statistically significant, an increase in HCC risk was observed among light smokers (1-20 pack-years) carrying GSTT1 null (OR = 1.7, 95% CI 0.6-4.7) and NAT2 slow acetylator (OR = 1.3, 95% CI 0.6-3.0) genotypes. In conclusion, there was no evidence for a gene-environment interaction in HCC risk for GSTM1, GSTT1 and NAT2 genotypes.     

Type 2 diabetes and hepatocellular carcinoma: a case-control study in patients with chronic hepatitis B

Type 2 diabetes has been suggested as an independent risk factor for the development of hepatocellular carcinoma (HCC). However, the role of Type 2 diabetes on the development of HCC in the presence of chronic hepatitis B (CHB) remains inconclusive. We conducted this hospital-based case-control study to evaluate the roles of Type 2 diabetes in HCC development in patients with CHB. From January 2004 to December 2008, a total of 6,275 eligible consecutive patients with chronic hepatitis B virus (HBV) infection were recruited. A total of 1,105 of them were patients with HBV-related HCC and 5,170 patients were CHB but without HCC. We used multivariate logistic regression models to investigate the association between Type 2 diabetes and HCC risk. The prevalence of Type 2 diabetes is higher among HCC patients without cirrhosis than among those with cirrhosis (12.1% vs. 6.7%, p=0.003). Type 2 diabetes was associated with a significantly high risk of HCC in female patients after adjusting for age, family history of HCC, city of residence, hepatitis B e antigen and cirrhosis with an odds ratio (95% confidence interval, CI) of 1.9 (1.1-3.4). Restricted analyses among female patients without cirrhosis indicated that Type 2 diabetes was strongly associated with HCC risk with adjusted odds ratio (95% CI) of 5.6 (2.2-14.1). In conclusion, Type 2 diabetes is independently associated with the increased risk of HCC in female CHB patients. Female CHB patients with Type 2 diabetes are of a high HCC risk population and should be considered for HCC close surveillance program.     

Cigarette smoking,alcohol, tea and coffee consumption and pancreas cancer risk: A case-control study from opole,Poland

A population-based, case-control study of pancreas cancer was undertaken in Opole, Poland, within the framework of the SEARCH Programme of the International Agency for Research on Cancer: this is the first aetiological study of pancreas cancer reported from Poland where the reported mortality rate has doubled since 1963. This study of pancreas cancer has provided some further supporting evidence of an association between increased pancreas risk with increasing levels of cigarette smoking. The risk rose with increasing lifetime cigarette consumption with a trend which was weakly significant (p=0.061). Findings regarding lifetime tea and coffee consumption were not consistent with intake of either beverage increasing the risk of this disease. There was a strongly significant trend of decreasing risk with increasing lifetime consumption of tea (p<0.001), which was also apparent when the analysis was restricted to subjects who were interviewed directly. For coffee consumption, which is low in Poland, there was also a negative association apparent in the data which was not statistically significant among the sub-set of subjects who were directly interviewed. The findings regarding alcoholic beverages were overall null, although the weakly positive trend in risk with spirits consumption (p=0.71) may deserve further investigation in view of the special nature of the source of spirits (vodka) in Poland.     

The role of hepatitis B and C viruses in hepatocellular carcinoma in a hepatitis B endemic area. A case-control study.

To investigate the role of hepatitis B (HBV) and C viruses (HCV) in hepatocellular carcinoma (HCC) in an HBV endemic area and elucidate the interaction of these two viruses, a case-control study of 128 patients with HCC and 384 age-matched and sex-matched control subjects was done. The positive rates of hepatitis B surface antigen (HBsAg, 77.3%, 99 of 128) and anti-HCV (19.5%, 25 of 128) in patients with HCC were significantly higher than in control subjects (P less than 0.001). Both HBsAg and anti-HCV were important risk factors for HCC (relative risks, 13.96 and 27.12, respectively), and the risk for HCC was elevated significantly to 40.05 (95% confidence interval, 12.57 to 127.6) when HBsAg and anti-HCV were considered simultaneously. These results suggested that HBV and HCV were associated highly with HCC in an HBV endemic area and that these two viruses might contribute independent but synergistic effects to the pathogenesis of HCC.