Risk Factors for Hepatocellular Carcinoma in the US
Risk Factors for Hepatocellular Carcinoma in the US
Objectives: Risk factors for hepatocellular carcinoma (HCC) include hepatitis B and C viruses (HBV, HCV), excessive alcohol consumption, rare genetic disorders and diabetes/obesity. The population attributable fractions (PAF) of these factors, however, have not been investigated in population-based studies in the United States.
Methods: Persons ≥68 years diagnosed with HCC (n=6,991) between 1994 and 2007 were identified in the SEER-Medicare database. A 5% random sample (n=255,702) of persons residing in SEER locations were selected for comparison. For each risk factor, odds ratios (ORs), 95% confidence intervals (95% CI) and PAFs were calculated.
Results: As anticipated, the risk of HCC was increased in relationship to each factor: HCV (OR 39.89, 95% CI: 36.29–43.84), HBV (OR 11.17, 95% CI: 9.18–13.59), alcohol-related disorders (OR 4.06, 95% CI: 3.82–4.32), rare metabolic disorders (OR 3.45, 95% CI: 2.97–4.02), and diabetes and/or obesity (OR 2.47, 95% CI: 2.34–2.61). The PAF of all factors combined was 64.5% (males 65.6%; females 62.2%). The PAF was highest among Asians (70.1%) and lowest among black persons (52.4%). Among individual factors, diabetes/obesity had the greatest PAF (36.6%), followed by alcohol-related disorders (23.5%), HCV (22.4%), HBV (6.3%) and rare genetic disorders (3.2%). While diabetes/obesity had the greatest PAF among both males (36.4%) and females (36.7%), alcohol-related disorders had the second greatest PAF among males (27.8%) and HCV the second greatest among females (28.1%). Diabetes/obesity had the greatest PAF among whites (38.9%) and Hispanics (38.1%), while HCV had the greatest PAF among Asians (35.4%) and blacks (34.9%). The second greatest PAF was alcohol-related disorders in whites (25.6%), Hispanics (30.1%) and blacks (and 18.5%) and HBV in Asians (28.5%).
Conclusions: The dominant risk factors for HCC in the United States among persons ≥68 years differ by sex and race/ethnicity. Overall, eliminating diabetes/obesity could reduce the incidence of HCC more than the elimination of any other factor.
Primary liver cancer, of which hepatocellular carcinoma (HCC) is the most common histological type, is the sixth most frequently occurring cancer in the world, and the second most common cause of cancer mortality. In the United States, the incidence of HCC has almost tripled over the past two decades, with ~20,000 individuals being newly diagnosed each year. Well-established HCC risk factors include alcoholic liver disease, chronic infection with hepatitis B and/or C virus (HBV, HCV), and some rare autoimmune or genetic conditions such as autoimmune hepatitis, hereditary hemochromatosis, alpha-1 antitrypsin deficiency, Wilson disease and some porphyrias. In concert with the worldwide epidemics of obesity and type 2 diabetes mellitus, increasing evidence suggests a significant contribution of these conditions to HCC risk. Recently, a large US study identified metabolic syndrome, as well as its individual components (i.e., obesity, diabetes), as significant risk factors for HCC.
The distribution of HCC risk factors in any population may vary over time and in different groups. In addition, estimates of relative risk or odds ratios (ORs) for any of the above HCC risk factors are not capable of describing their contribution to tumor incidence, as the latter is also driven by the prevalence of the factor in the general population. Better characterizations of the impact of the risk factors on the incidence of HCC are the population attributable fractions (PAF), which account both for the strength of the association between exposure and outcome, and also for the prevalence of the exposure in the population. Studies have reported PAFs for HCC in Italy, Europe and worldwide, but PAFs for the US have not been previously reported. Therefore, the goal of the current study was to investigate the PAFs for HCC using data from the SEER-Medicare linked database.
Abstract and Introduction
Abstract
Objectives: Risk factors for hepatocellular carcinoma (HCC) include hepatitis B and C viruses (HBV, HCV), excessive alcohol consumption, rare genetic disorders and diabetes/obesity. The population attributable fractions (PAF) of these factors, however, have not been investigated in population-based studies in the United States.
Methods: Persons ≥68 years diagnosed with HCC (n=6,991) between 1994 and 2007 were identified in the SEER-Medicare database. A 5% random sample (n=255,702) of persons residing in SEER locations were selected for comparison. For each risk factor, odds ratios (ORs), 95% confidence intervals (95% CI) and PAFs were calculated.
Results: As anticipated, the risk of HCC was increased in relationship to each factor: HCV (OR 39.89, 95% CI: 36.29–43.84), HBV (OR 11.17, 95% CI: 9.18–13.59), alcohol-related disorders (OR 4.06, 95% CI: 3.82–4.32), rare metabolic disorders (OR 3.45, 95% CI: 2.97–4.02), and diabetes and/or obesity (OR 2.47, 95% CI: 2.34–2.61). The PAF of all factors combined was 64.5% (males 65.6%; females 62.2%). The PAF was highest among Asians (70.1%) and lowest among black persons (52.4%). Among individual factors, diabetes/obesity had the greatest PAF (36.6%), followed by alcohol-related disorders (23.5%), HCV (22.4%), HBV (6.3%) and rare genetic disorders (3.2%). While diabetes/obesity had the greatest PAF among both males (36.4%) and females (36.7%), alcohol-related disorders had the second greatest PAF among males (27.8%) and HCV the second greatest among females (28.1%). Diabetes/obesity had the greatest PAF among whites (38.9%) and Hispanics (38.1%), while HCV had the greatest PAF among Asians (35.4%) and blacks (34.9%). The second greatest PAF was alcohol-related disorders in whites (25.6%), Hispanics (30.1%) and blacks (and 18.5%) and HBV in Asians (28.5%).
Conclusions: The dominant risk factors for HCC in the United States among persons ≥68 years differ by sex and race/ethnicity. Overall, eliminating diabetes/obesity could reduce the incidence of HCC more than the elimination of any other factor.
Introduction
Primary liver cancer, of which hepatocellular carcinoma (HCC) is the most common histological type, is the sixth most frequently occurring cancer in the world, and the second most common cause of cancer mortality. In the United States, the incidence of HCC has almost tripled over the past two decades, with ~20,000 individuals being newly diagnosed each year. Well-established HCC risk factors include alcoholic liver disease, chronic infection with hepatitis B and/or C virus (HBV, HCV), and some rare autoimmune or genetic conditions such as autoimmune hepatitis, hereditary hemochromatosis, alpha-1 antitrypsin deficiency, Wilson disease and some porphyrias. In concert with the worldwide epidemics of obesity and type 2 diabetes mellitus, increasing evidence suggests a significant contribution of these conditions to HCC risk. Recently, a large US study identified metabolic syndrome, as well as its individual components (i.e., obesity, diabetes), as significant risk factors for HCC.
The distribution of HCC risk factors in any population may vary over time and in different groups. In addition, estimates of relative risk or odds ratios (ORs) for any of the above HCC risk factors are not capable of describing their contribution to tumor incidence, as the latter is also driven by the prevalence of the factor in the general population. Better characterizations of the impact of the risk factors on the incidence of HCC are the population attributable fractions (PAF), which account both for the strength of the association between exposure and outcome, and also for the prevalence of the exposure in the population. Studies have reported PAFs for HCC in Italy, Europe and worldwide, but PAFs for the US have not been previously reported. Therefore, the goal of the current study was to investigate the PAFs for HCC using data from the SEER-Medicare linked database.
