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Background and aims: Various smoking behaviors, including smoking initiation, age of initiation, heaviness of smoking and smoking cessation, have been individually related to the risk of mortality; however, no study has assessed these smoking behaviors jointly in relation to mortality. Our study aimed to measure prospectively the association of panoramic smoking burden (PSB), generated from the four aforementioned smoking behaviors, with all‐cause and cause‐specific mortality, and measure whether such associations are modified by genetic variations. Design Prospective cohort study. Setting: UK Biobank. Participants: A total of 360 937 participants aged between 37 and 73 years were enrolled in 2006–10 and ‐followed‐up to 2018. Measurements The exposure was PSB, constructed based on four smoking behaviors including smoking initiation, age of initiation, heaviness of smoking and smoking cessation in a weighted method. A genetically determined PSB was also constructed with smoking‐associated single nucleotide polymorphisms (SNPs) and categorized into tertiles. The primary outcomes were all‐cause and cause‐specific mortality. Findings We identified 15 968 deaths [9022 from cancer and 5092 from cardiovascular disease (CVD)] over a median of 11.36 years' follow‐up. For all‐cause mortality, compared with participants with the PSB of zero, the hazard ratios of participants who had a PSB of one, two, three and four were 1.23 [95% confidence intervals (CI) = 1.18–1.29), 1.66 (95% CI = 1.59–1.75), 3.33 (95% CI = 3.17–3.51) and 5.76 (95% CI = 4.66–7.13), respectively. Among participants within each genetic risk category, low and intermediate PSB were associated with 45–58% reduced risk of all‐cause death compared with high PSB. Analysis of population‐attributable risk percentage indicated that 21.9, 19.1 and 24.7% of all‐cause‐, cancer‐ and CVD‐specific death could have been avoided if all ever smokers initiated smoking after age 18 years, smoked < 20 cigarettes/day and quit smoking. Conclusions: The panoramic smoking burden, based on smoking initiation, age of initiation, heaviness of smoking and smoking cessation, appears to be associated with all‐cause and cause‐specific mortality in a gradient manner with increasing panoramic smoking burden independent of other traditional and genetic risk factors. [ABSTRACT FROM AUTHOR]

Aim: To test the association of alcohol consumption with total and cause‐specific mortality risk. Design Prospective observational multi‐centre population‐based study. Setting: Sixteen cohorts (15 from Europe) in the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Project. Participants: A total of 142 960 individuals (mean age 50 ± 13 years, 53.9% men). Measurements Average alcohol intake by food frequency questionnaire, total and cause‐specific mortality. Findings In comparison with life‐time abstainers, consumption of alcohol less than 10 g/day was associated with an average 11% [95% confidence interval (CI) = 7–14%] reduction in the risk of total mortality, while intake > 20 g/day was associated with a 13% (95% CI = 7–20%) increase in the risk of total mortality. Comparable findings were observed for cardiovascular (CV) deaths. With regard to cancer, drinking up to 10 g/day was not associated with either mortality risk reduction or increase, while alcohol intake > 20 g/day was associated with a 22% (95% CI = 10–35%) increased risk of mortality. The association of alcohol with fatal outcomes was similar in men and women, differed somewhat between countries and was more apparent in individuals preferring wine, suggesting that benefits may not be due to ethanol but other ingredients. Mediation analysis showed that high‐density lipoprotein cholesterol explained 2.9 and 18.7% of the association between low alcohol intake and total as well as CV mortality, respectively. Conclusions: In comparison with life‐time abstainers, consuming less than one drink per day (nadir at 5 g/day) was associated with a reduced risk of total, cardiovascular and other causes mortality, except cancer. Intake of more than two drinks per day was associated with an increased risk of total, cardiovascular and especially cancer mortality. [ABSTRACT FROM AUTHOR]