Jerry Polesel

The impact of obesity and diabetes mellitus on the risk of hepatocellular carcinoma

BACKGROUND Obesity has been associated to increased hepatocellular carcinoma (HCC) risk, but studies on the topic do not fully account for hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. Likewise, an increased risk has been reported for diabetes mellitus (DM) but whether DM is an independent risk factor has not been established yet. To evaluate the association of obesity and DM with HCC risk, we conducted a hospital-based, case-control study in two Italian areas. PATIENTS AND METHODS From 1999 to 2003, 185 HCC cases and 404 hospital controls were enrolled. Blood samples were obtained for HBV and HCV screening. RESULTS After allowance for known risk factors, body mass index >/=30 kg/m(2) [odds ratio (OR) = 1.9, 95% confidence interval (CI) 0.9-3.9] and DM (OR = 3.7, 95% CI 1.7-8.4) were associated to HCC risk. These associations persisted (OR = 3.5, 95% CI 1.6-7.7 for obesity; OR = 3.5, 95% CI 1.3-9.2 for DM) among subjects without HBV and/or HCV infection. Overall, 23% of HCC cases seemed attributable to these conditions, and this figure rose to 37% among subjects without HBV and/or HCV infections. CONCLUSIONS The present study provides further evidence that obesity and DM increase HCC risk and that these factors may explain a relevant proportion of cases among subjects without markers of HBV/HCV infection.

Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4)

BACKGROUND To evaluate the dose-response relationship between cigarette smoking and pancreatic cancer and to examine the effects of temporal variables. METHODS We analyzed data from 12 case-control studies within the International Pancreatic Cancer Case-Control Consortium (PanC4), including 6507 pancreatic cases and 12 890 controls. We estimated summary odds ratios (ORs) by pooling study-specific ORs using random-effects models. RESULTS Compared with never smokers, the OR was 1.2 (95% confidence interval [CI] 1.0-1.3) for former smokers and 2.2 (95% CI 1.7-2.8) for current cigarette smokers, with a significant increasing trend in risk with increasing number of cigarettes among current smokers (OR=3.4 for ≥35 cigarettes per day, P for trend<0.0001). Risk increased in relation to duration of cigarette smoking up to 40 years of smoking (OR=2.4). No trend in risk was observed for age at starting cigarette smoking, whereas risk decreased with increasing time since cigarette cessation, the OR being 0.98 after 20 years. CONCLUSIONS This uniquely large pooled analysis confirms that current cigarette smoking is associated with a twofold increased risk of pancreatic cancer and that the risk increases with the number of cigarettes smoked and duration of smoking. Risk of pancreatic cancer reaches the level of never smokers ∼20 years after quitting.

Pattern of cancer risk in persons with AIDS in Italy in the HAART era

A record-linkage study was carried out between the Italian AIDS Registry and 24 Italian cancer registries to compare cancer excess among persons with HIV/AIDS (PWHA) before and after the introduction of highly active antiretroviral therapy (HAART) in 1996. Standardised incidence ratios (SIR) were computed in 21951 AIDS cases aged 16–69 years reported between 1986 and 2005. Of 101 669 person-years available, 45 026 were after 1996. SIR for Kaposi sarcoma (KS) and non-Hodgkin lymphoma greatly decreased in 1997–2004 compared with 1986–1996, but high SIRs for KS persisted in the increasingly large fraction of PWHA who had an interval of <1 year between first HIV-positive test and AIDS diagnosis. A significant excess of liver cancer (SIR=6.4) emerged in 1997–2004, whereas the SIRs for cancer of the cervix (41.5), anus (44.0), lung (4.1), brain (3.2), skin (non-melanoma, 1.8), Hodgkin lymphoma (20.7), myeloma (3.9), and non-AIDS-defining cancers (2.2) were similarly elevated in the two periods. The excess of some potentially preventable cancers in PWHA suggests that HAART use must be accompanied by cancer-prevention strategies, notably antismoking and cervical cancer screening programmes. Improvements in the timely identification of HIV-positive individuals are also a priority in Italy to avoid the adverse consequences of delayed HAART use.

Non-Hodgkin lymphoma incidence in the Swiss HIV Cohort Study before and after highly active antiretroviral therapy

Objective:To assess the long-term effect of HAART on non-Hodgkin lymphoma (NHL) incidence in people with HIV (PHIV). Design:Follow-up of the Swiss HIV Cohort Study (SHCS). Methods:Between 1984 and 2006, 12 959 PHIV contributed a total of 75 222 person-years (py), of which 36 787 were spent under HAART. Among these PHIV, 429 NHL cases were identified from the SHCS dataset and/or by record linkage with Swiss Cantonal Cancer Registries. Age- and gender-standardized incidence was calculated and Cox regression was used to estimate hazard ratios (HR). Results:NHL incidence reached 13.6 per 1000 py in 1993–1995 and declined to 1.8 in 2002–2006. HAART use was associated with a decline in NHL incidence [HR = 0.26; 95% confidence interval (CI), 0.20–0.33], and this decline was greater for primary brain lymphomas than other NHL. Among non-HAART users, being a man having sex with men, being 35 years of age or older, or, most notably, having low CD4 cell counts at study enrolment (HR = 12.26 for < 50 versus ≥ 350 cells/μl; 95% CI, 8.31–18.07) were significant predictors of NHL onset. Among HAART users, only age was significantly associated with NHL risk. The HR for NHL declined steeply in the first months after HAART initiation (HR = 0.46; 95% CI, 0.27–0.77) and was 0.12 (95% CI, 0.05–0.25) 7 to10 years afterwards. Conclusions:HAART greatly reduced the incidence of NHL in PHIV, and the influence of CD4 cell count on NHL risk. The beneficial effect remained strong up to 10 years after HAART initiation.

Influence of HIV-related immunodeficiency on the risk of hepatocellular carcinoma.

Objective:To investigate HIV-related immunodeficiency as a risk factor for hepatocellular carcinoma (HCC) among persons infected with HIV, while controlling for the effect of frequent coinfection with hepatitis C and B viruses. Design:A case–control study nested in the Swiss HIV Cohort Study. Methods:Twenty-six HCC patients were identified in the Swiss HIV Cohort Study or through linkage with Swiss Cancer Registries, and were individually matched to 251 controls according to Swiss HIV Cohort Study centre, sex, HIV-transmission category, age and year at enrolment. Odds ratios and corresponding confidence intervals were estimated by conditional logistic regression. Results:All HCC patients were positive for hepatitis B surface antigen or antibodies against hepatitis C virus. HCC patients included 14 injection drug users (three positive for hepatitis B surface antigen and 13 for antibodies against hepatitis C virus) and 12 men having sex with men/heterosexual/other (11 positive for hepatitis B surface antigen, three for antibodies against hepatitis C virus), revealing a strong relationship between HIV transmission route and hepatitis viral type. Latest CD4+ cell count [Odds ratio (OR) per 100 cells/μl decrease = 1.33, 95% confidence interval (CI) 1.06–1.68] and CD4+ cell count percentage (OR per 10% decrease = 1.65, 95% CI 1.01–2.71) were significantly associated with HCC. The effects of CD4+ cell count were concentrated among men having sex with men/heterosexual/other rather than injecting drug users. Highly active antiretroviral therapy use was not significantly associated with HCC risk (OR for ever versus never = 0.59, 95% confidence interval 0.18–1.91). Conclusion:Lower CD4+ cell counts increased the risk for HCC among persons infected with HIV, an effect that was particularly evident for hepatitis B virus-related HCC arising in non-injecting drug users.

Hepatitis Viruses, Alcohol, and Tobacco in the Etiology of Hepatocellular Carcinoma in Italy

Mortality rates of hepatocellular carcinoma (HCC) are high in Italy compared with other Western countries. To elucidate further the role of hepatitis B virus (HBV), hepatitis C virus (HCV), alcohol drinking, and tobacco smoking in the etiology of HCC, we carried out a hospital-based case-control study in two areas of Italy: the province of Pordenone in the Northeast and the town of Naples in the South. A total of 229 HCC cases (median age, 66 years) and 431 controls (median age, 65 years) answered a questionnaire and provided blood samples between 1999 and 2002. Odds ratios (OR), percent attributable risks, and corresponding 95% confidence intervals were computed using unconditional multiple logistic regression. ORs for hepatitis B surface antigen (HBsAg) positive versus HBsAg negative and for anti-HCV antibody positive versus anti-HCV antibody negative were 20.2 and 15.6, respectively. Positivity for both markers was associated with an OR of 51.6. Sensitive molecular techniques applied to sera in a subset of HCC cases disclosed a very small number of occult hepatites. Maximal lifetime alcohol intake of ≥35 versus <7 drinks/wk was associated with an HBV/HCV adjusted OR of 5.9. Tobacco smoking was unrelated to HCC risk overall but seemed to enhance HCC risk among virus carriers. Overall, 61% of HCC were attributable to HCV, 13% to HBV, and 18% to heavy alcohol drinking. In conclusion, our study confirms the importance of HCV in HCC etiology in Italy where the widespread dissemination of the virus dates back four or five decades. (Cancer Epidemiol Biomarkers Prev 2006;15(4):683–9)

Alcohol consumption and pancreatic cancer: A pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4)

BACKGROUND Heavy alcohol drinking has been related to pancreatic cancer, but the issue is still unsolved. METHODS To evaluate the role of alcohol consumption in relation to pancreatic cancer, we conducted a pooled analysis of 10 case-control studies (5585 cases and 11,827 controls) participating in the International Pancreatic Cancer Case-Control Consortium. We computed pooled odds ratios (ORs) by estimating study-specific ORs adjusted for selected covariates and pooling them using random effects models. RESULTS Compared with abstainers and occasional drinkers (< 1 drink per day), we observed no association for light-to-moderate alcohol consumption (≤ 4 drinks per day) and pancreatic cancer risk; however, associations were above unity for higher consumption levels (OR = 1.6, 95% confidence interval 1.2-2.2 for subjects drinking ≥ 9 drinks per day). Results did not change substantially when we evaluated associations by tobacco smoking status, or when we excluded participants who reported a history of pancreatitis, or participants whose data were based upon proxy responses. Further, no notable differences in pooled risk estimates emerged across strata of sex, age, race, study type, and study area. CONCLUSION This collaborative-pooled analysis provides additional evidence for a positive association between heavy alcohol consumption and the risk of pancreatic cancer.

Risk of cancer in persons with AIDS in Italy, 1985-1998

A record linkage was carried out between the Italian Registry of AIDS and 19 Cancer Registries (CRs), which covered 23% of the Italian population, to estimate the overall cancer burden among persons with HIV or AIDS (PWHA) in Italy, according to various characteristics. Observed and expected numbers of cancer and standardised incidence ratios (SIRs) were assessed until 1998 in 12 104 PWHA aged 15–69 years, for a total of 60 421 person-years. Significantly increased SIRs were observed for Kaposis sarcoma (KS, 1749-fold higher than the general population), non-Hodgkins lymphomas (NHL, 352), and invasive cervical cancer (22). SIR was significantly elevated also for cancer of the anus (34), lung cancer (2.4), brain tumours (4.4), Hodgkins disease (16), and leukaemias (5.3). The majority of lung and brain cancers were not histologically confirmed, and the possibility of misclassification with KS or NHL cannot be ruled out. The SIR for all non-AIDS-defining cancers was 2.2 in men and 2.5 in women. Intravenous drug users showed significantly more elevated SIRs for lung cancer (9.4), and brain tumours (6.7) than other transmission categories (SIR=1.4 and 2.3, respectively). This study confirmed increased SIRs for haemolymphopoietic neoplasms other than NHL in PWHA, although many-fold smaller than for NHL. An association with human papillomavirus-related cancers was also confirmed.

Kaposi sarcoma incidence in the Swiss HIV Cohort Study before and after highly active antiretroviral therapy

Between 1984 and 2006, 12 959 people with HIV/AIDS (PWHA) in the Swiss HIV Cohort Study contributed a total of 73 412 person-years (py) of follow-up, 35 551 of which derived from PWHA treated with highly active antiretroviral therapy (HAART). Five hundred and ninety-seven incident Kaposi sarcoma (KS) cases were identified of whom 52 were among HAART users. Cox regression was used to estimate hazard ratios (HR) and corresponding 95% confidence intervals (CI). Kaposi sarcoma incidence fell abruptly in 1996–1998 to reach a plateau at 1.4 per 1000 py afterwards. Men having sex with men and birth in Africa or the Middle East were associated with KS in both non-users and users of HAART but the risk pattern by CD4 cell count differed. Only very low CD4 cell count (<50 cells μl−1) at enrolment or at HAART initiation were significantly associated with KS among HAART users. The HR for KS declined steeply in the first months after HAART initiation and continued to be low 7–10 years afterwards (HR, 0.06; 95% CI, 0.02–0.17). Thirty-three out of 52 (63.5%) KS cases among HAART users arose among PWHA who had stopped treatment or used HAART for less than 6 months.

Metabolic syndrome and hepatocellular carcinoma risk.

Background:Hepatocellular carcinoma (HCC) has been associated to diabetes and obesity, but a possible association with the metabolic syndrome (MetS) and its potential interaction with hepatitis is open to discussion.Methods:We analysed data from an Italian case–control study, including 185 HCC cases and 404 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed from unconditional logistic regression models.Results:Among the MetS components, diabetes and obesity (i.e, body mass index (BMI)⩾30 kg m−2) were positively associated to HCC risk, with ORs of 4.33 (95% CI, 1.89–9.86) and 1.97 (95% CI, 1.03–3.79), respectively. The ORs for the MetS were 4.06 (95% CI, 1.33–12.38) defining obesity as BMI⩾25, and 1.92 (95% CI, 0.38–9.76) defining it as BMI⩾30. The risk increased with the number of MetS components, up to an almost four-fold excess risk among subjects with ⩾2 MetS factors. Among subjects without chronic infection with hepatitis B and/or C, the OR for those with ⩾2 MetS components was over six-fold elevated. There was no consistent association in subjects with serological evidence of hepatitis B and/or C infection.Conclusion:This study found that the risk of HCC increases with the number of MetS components in subjects not chronically infected with hepatitis viruses.