Alcohol consumption is a known cause of cancer, but its role in the etiology of second primary (metachronous) cancer is uncertain. Associations between alcohol intake up until study enrollment (pre-diagnosis) and risk of metachronous cancer were examined in 9,435 participants in the Melbourne Collaborative Cohort Study who were diagnosed with their first invasive cancer after enrollment (1990-94). Follow-up was from date of first invasive cancer until diagnosis of metachronous cancer, death or censor date (February 2018), whichever came first. Alcohol intake for 10-year periods from age 20 until decade encompassing baseline using recalled beverage-specific frequency and quantity was used to calculate baseline and lifetime intakes, and group-based intake trajectories. We estimated hazard ratios (HR) and 95% confidence intervals (CI), adjusted for potential confounders. After a mean follow-up of 7 years, 1,512 metachronous cancers were identified. A 10 g/day increment in pre-diagnosis lifetime alcohol intake (HR=1.03, 95% CI:1.00-1.06;p =0.02) and an intake of ≥60 g/day (HR=1.32, 95% CI:1.01-1.73) were associated with increased metachronous cancer risk. We observed positive associations (per 10 g/day increment) for metachronous colorectal (HR=1.07, 95% CI:1.00-1.14), upper aero-digestive tract (UADT) (HR=1.16, 95% CI:1.00-1.34) and kidney cancer (HR=1.24, 95% CI:1.10-1.39). Although these findings were partly explained by effects of smoking, the association for kidney cancer remained unchanged when current smokers or obese individuals were excluded. Alcohol intake trajectories over the life course confirmed associations with metachronous cancer risk. Pre-diagnosis long-term alcohol intake, and particularly heavy drinking, may increase the risk of metachronous cancer, particularly of the colorectum, UADT and kidney.
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