Influences of tobacco and alcohol use on hepatocellular carcinoma survival

Abstract

Prognosis of hepatocellular carcinoma (HCC) is generally poor. The role of modifiable lifestyle factors on HCC survival has been less studied. To examine whether prediagnosis smoking and alcohol affected HCC survival stratified by viral etiology, we conducted a prospective cohort study of 2,273 (1990 with viral hepatitis and 283 without) incident HCC cases aged 20-75 years who were enrolled between 1997 and 2004 from a Taiwanese multicenter study, and followed up through 2007. Information on habitual smoking and alcohol consumption was obtained at baseline through personal interview. After follow-up to a maximum of 10 years, 1,757 participants died and 1,488 (84.7%) were attributed to HCC. Prediagnosis smoking and alcohol worsened prognosis independent of each other and clinical predictors. The effects of both risky behaviors were limited to viral hepatitis-related HCC and more profound among those with early-stage HCC. Risk for HCC-specific mortality increased with increasing pack-years smoked and ethanol intake (all p < 0.001 for trend), with an additive effect shown for the two habits [hazard ratio (HR) for alcohol 46.2 g/day and 10 pack-years 5 1.72, 95% confidence interval (CI) 5 1.45-2.05]. For either habit, cessation reduced HCC-specific mortality, but a significant mortality benefit occurred 10 years after abstinence (quitting smoking 10 years vs. continuing smokers: HR 5 0.77, 95% CI 5 0.61-0.97; quitting drinking 10 years vs. continuing drinkers: HR 5 0.74, 95% CI 5 0.56-0.98). In conclusion, among patients with viral hepatitis-related HCC, prediagnosis smoking and alcohol have a deleterious effect on HCC survival. Quitting smoking or drinking alcohol could reduce the excess risk, but only after a long interval of cessation.Hepatocellular carcinoma (HCC) is one of the world's leading cancer threats associated with death.1 The prognosis of advanced HCC remains poor. With marked improvement in the early detection and management of HCC during recent decades; however, up to around 60% of early-stage HCC patients may survive without recurrence for 5 or even 7 years.2-4 Established prognostic predictors include the degrees of liver damage, tumor burden and serum a-fetoprotein values.2-4 Although many studies have addressed these and other prognostic factors, 2-5 there has been limited exploration of the influence of modifiable lifestyle factors on HCC prognosis.Both alcohol consumption and cigarette smoking have been associated with increased risk of HCC in many epidemiological studies, although the results are somewhat inconsistent.6-12 Heavy drinking is a major cause of liver cirrhosis, 13,14 which underlies HCC and contributes to poor prognosis of HCC.2-4,11 Tobacco-related carcinogens can initiate liver tumor formation and inactivate tumor suppressor genes via promoter hypermethylation or mutation in animal models, [15][16][17][18][19] yet the information on the role of prediagnostic smoking in HCC survival is limited. 20 Whether smoking cessation can improve survival rates remains unclear.Using a multic...

Role of aetiology, diabetes, tobacco smoking and hypertension in hepatocellular carcinoma survival

“…These data are in contrast with two recent Asian studies that found an association between tobacco use and recurrence after surgery and overall survival in HBV/HCV-related HCC [15,16]. However, because continued smoking after HCC treatment may be more relevant than smoking before HCC diagnosis, data on post-treatment smoking habit are needed.…”

“…A c c e p t e d M a n u s c r i p t 4 Tobacco smoking has been recognized as a risk factor for various cancers, including HCC [14]; further, two recent investigations [15,16] found an association between continued smoking after diagnosis and worse prognosis for HCC Lastly, hypertension has been investigated as a possible independent predictor of HCC survival [17], although more conclusive data are required.…”

Incidence and mortality of liver cancer and their relationship with the human development index in the world

“…Another reason for the difference in incidence in different regions was Human papillomavirus (HPV), which is responsible for stomach, liver and cervical cancers (Vineis and Wild, 2014). Other etiologies for liver cancer are modifiable risk factors, such as smoking, alcohol, contaminated injections in health care centers, immigration and obesity (Chuang et al, 2009;Ezzati and Riboli, 2013;Franceschi and Wild, 2013;Shih et al, 2012). The relative risk associated with family history of liver cancer is 2.6 and the cancer is also significantly more common in men (Huang et al, 2011;Yang et al, 2014).…”

European Code against Cancer 4th Edition: Alcohol drinking and cancer

“…In both genders combined, dose-response analyses show RRs of 1.07 (95%CI: 1.04-1.10), 1.38 (95%CI: 1.28-1.50) and 1.82 (95%CI: 1.41-2.35) at 10, 50 and 100 g/day of alcohol consumption, respectively [43]. Associations of alcohol consumption with hepatocellular carcinoma are generally found at high intakes [44] with significant increased risks of about 30-40% at consumption levels >40 g/day [45][46][47][48]. An increased risk at low to moderate alcohol consumption is also reported [4,47,49].…”