ABSTRACT
Thailand is among countries with the highest global incidence and mortality rates of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). While viral hepatitis and liver fluke infections have been associated with HCC and iCCA, respectively, other environmental risk factors, overall risk factor commonality and combinatorial roles, and effects on survival have not been systematically examined. We conducted a TIGER-LC consortium-based population study covering all high-incidence areas of both malignancies across Thailand: 837 HCC, 1474 iCCA, and 1112 controls (2011-2019) were comprehensively queried on lifelong environmental exposures, lifestyle, and medical history. Multivariate logistic regression and Cox proportional hazards analyses were used to evaluate risk factors and associated survival patterns. Our models identified shared risk factors between HCC and iCCA, such as viral hepatitis infection, liver fluke infection, and diabetes, including novel and shared associations of agricultural pesticide exposure (OR range of 1.50; 95% CI: 1.06-2.11 to 2.91; 95% CI: 1.82-4.63) along with vulnerable sources of drinking water. Most patients had multiple risk factors, magnifying their risk considerably. Patients with lower risk levels had better survival in both HCC (HR 0.78; 95% CI: 0.64-0.96) and iCCA (HR 0.84; 95% CI: 0.70-0.99). Risk factor co-exposures and their common associations with HCC and iCCA in Thailand emphasize the importance for future prevention and control measures, especially in its large agricultural sector. The observed mortality patterns suggest ways to stratify patients for anticipated survivorship and develop plans to support medical care of longer-term survivors, including behavioral changes to reduce exposures.
Subject(s)
Bile Duct Neoplasms , Carcinoma, Hepatocellular , Cholangiocarcinoma , Liver Neoplasms , Humans , Thailand/epidemiology , Cholangiocarcinoma/epidemiology , Cholangiocarcinoma/etiology , Cholangiocarcinoma/mortality , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/mortality , Liver Neoplasms/epidemiology , Liver Neoplasms/etiology , Male , Female , Middle Aged , Bile Duct Neoplasms/epidemiology , Bile Duct Neoplasms/etiology , Risk Factors , Aged , Incidence , Adult , Environmental Exposure/adverse effects , Case-Control StudiesABSTRACT
BACKGROUND: Reducing cigarettes per day may lower the risk of lung cancer compared with continuing to smoke at the same intensity. Other changes in smoking behaviors, such as increasing cigarette consumption or quitting for a period and relapsing, may also affect lung cancer risk. METHODS: We examined changes in smoking status and cigarettes per day among 24â613 Finnish male smokers aged 50-69 years who participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Longitudinal data on smoking were collected during study follow-up visits 3 times a year (approximately every 4 months) between 1985 and 1993. Incident lung cancer patients through 2012 were identified by the Finnish Cancer Registry. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression. RESULTS: Compared with smoking 20 cigarettes per day continuously across the intervention period, reducing an average of 5 cigarettes per day per year while smoking was associated with a 20% lower risk of lung cancer (95% CI = 0.71 to 0.90). A substantially lower risk of lung cancer was also observed when participants smoked at 50% (RR = 0.72, 95% CI = 0.57 to 0.90) and 10% (RR = 0.55, 95% CI = 0.36 to 0.83) of study visits, relative to smoked at 100% of study visits. CONCLUSIONS: Smokers may lower their risk of lung cancer by reducing smoking intensity (cigarettes per day while smoking) and the time they smoke. However, quitting smoking completely is the most effective way for smokers to reduce their risk of lung cancer.