Longer duration and earlier age of onset of paternal betel chewing and smoking increase metabolic syndrome risk in human offspring, independently, in a community-based screening program in Taiwan

Background: Transgenerational effects of paternal Areca catechu nut chewing on offspring metabolic syndrome (MetS) risk in humans, on obesity and diabetes mellitus experimentally, and of paternal smoking on offspring obesity, are reported, likely attributable to genetic and epigenetic effects previously reported in betel-associated disease. We aimed to determine the effects of paternal smoking, and betel chewing, on the risks of early MetS in human offspring. Methods: The 13 179 parent-child trios identified from 238 364 Taiwanese aged ≥20 years screened at 2 community-based integrated screening sessions were tested for the effects of paternal smoking, areca nut chewing, and their duration prefatherhood on age of detecting offspring MetS at screen by using a Cox proportional hazards regression model. Results: Offspring MetS risks increased with prefatherhood paternal areca nutusage (adjusted hazard ratio, 1.77; 95% confidence interval [CI], 1.23-2.53) versus nonchewing fathers (adjusted hazard ratio, 3.28; 95% CI, 1.67-6.43) with >10 years paternal betel chewing, 1.62 (95% CI, 0.88-2.96) for 5 to 9 years, and 1.42 (95% CI, 0.80-2.54) for <5 years betel usage prefatherhood (P trend =0.0002), with increased risk (adjusted hazard ratio, 1.95; 95% CI, 1.26-3.04) for paternal areca nut usage from 20 to 29 years of age, versus from >30 years of age (adjusted hazard ratio,1.61; 95% CI, 0.22-11.69). MetS offspring risk for paternal smoking increased dosewise (P trend <0.0001) with earlier age of onset (P trend =0.0009), independently. Conclusions: Longer duration of paternal betel quid chewing and smoking, prefatherhood, independently predicted early occurrence of incident MetS in offspring, corroborating previously reported transgenerational effects of these habits, and supporting the need for habit-cessation program provision.