Transgenerational effects of betel-quid chewing on the development of the metabolic syndrome in the Keelung Community-based Integrated Screening Program

Background: The transgenerational metabolic effects of betel-quid chewing have been reported in mice but not in humans. Objective: This study aimed to determine whether exposure to paternal chewing of betel nut quids led to an increased risk of early manifestation of the metabolic syndrome (MetS) in human offspring. Design: The subjects were selected from 66 971 residents aged > 19 y who attended a community-based Integrated Screening Program in Taiwan and who were identified as parent-child trios (n = 5037). Using a population-based, parent-child study design, we compared the mean ages of offspring with MetS at entry between those who were exposed and those who were unexposed to paternal chewing of quids containing betel nut. Cox proportional hazards regression models were used to estimate adjusted hazard ratios and to assess dose-response relations for paternal betel-quid exposure. Results: The offspring who were exposed to paternal betel-quid chewing were younger than those who were not exposed, regardless of MetS status; they also had a 2.14-fold increase in the risk of early manifestation of MetS (adjusted hazard ratio = 2.14; 95% CI: 1.25, 3.66) after control for environmental and other risk factors, including personal betel chewing. Significant dose-response relations were found between the risk of early MetS and the quantity and duration of paternal exposure to betel quids. In the absence of MetS in either parent and of betel-quid consumption by the offspring, paternal exposure to betel quids increased the risk of early manifestation of MetS in offspring 2.53-fold (95% CI: 1.03, 2.64) compared with paternal nonexposure. Conclusion: Our findings suggest that exposure to paternal betel-quid chewing increases the risk of early manifestation of MetS in human offspring in a dose-dependent manner.