The association of lifetime alcohol use with mortality and cancer risk in older adults: A cohort study

Abstract

Background: While current research is largely consistent as to the harms of heavy drinking in terms of both cancer incidence and mortality, there are disparate messages regarding the safety of light-moderate alcohol consumption, which may confuse public health messages. We aimed to evaluate the association between average lifetime alcohol intakes and risk of both cancer incidence and mortality.

Methods and findings: We report a population-based cohort study using data from 99,654 adults (68.7% female), aged 55-74 years, participating in the U.S. Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Cox proportional hazards models assessed the risk of overall and cause-specific mortality, cancer incidence (excluding nonmelanoma skin cancer), and combined risk of cancer and death across categories of self-reported average lifetime alcohol intakes, with adjustment for potential confounders. During 836,740 person-years of follow-up (median 8.9 years), 9,599 deaths and 12,763 primary cancers occurred. Positive linear associations were observed between lifetime alcohol consumption and cancer-related mortality and total cancer incidence. J-shaped associations were observed between average lifetime alcohol consumption and overall mortality, cardiovascular-related mortality, and combined risk of death or cancer. In comparison to lifetime light alcohol drinkers (1-3 drinks per week), lifetime never or infrequent drinkers (<1 drink/week), as well as heavy (2-<3 drinks/day) and very heavy drinkers (3+ drinks/day) had increased overall mortality and combined risk of cancer or death. Corresponding hazard ratios (HRs) and 95% confidence intervals (CIs) for combined risk of cancer or death, respectively, were 1.09 (1.01-1.13) for never drinkers, 1.08 (1.03-1.13) for infrequent drinkers, 1.10 (1.02-1.18) for heavy drinkers, and 1.21 (1.13-1.30) for very heavy drinkers. This analysis is limited to older adults, and residual confounding by socioeconomic factors is possible.

Conclusions: The study supports a J-shaped association between alcohol and mortality in older adults, which remains after adjustment for cancer risk. The results indicate that intakes below 1 drink per day were associated with the lowest risk of death.

Trial registration: NCT00339495 (ClinicalTrials.gov).

Fig 1. STROBE flow diagram of participant inclusion.

Fig 2

Restricted cubic splines for the association between average lifetime alcohol intake and overall mortality (A, 4 knots), cardiovascular-related mortality (5 knots), cancer-related mortality (C, linear), total cancer risk (D, linear), risk of alcohol-related cancers (E, linear), and risk of cancer or death (F, 4 knots/3 splines) in men and women combined. Results are adjusted for gender, study centre, race, BMI, randomisation group, smoking status, year of DHQ completion, marital status, educational attainment, family history of cancer, HRT use (women only), energy intake, red meat intakes per 1,000 kcal, processed meat intakes per 1,000 kcal, coffee intake, fruit and vegetable intake, fibre intake, and calcium intake). Akaike's information criterion and likelihood ratio tests were used to investigate if there was a significant improvement to the model fit when fitting restricted cubic spline models, with varying number of knots, compared to a linear model with average lifetime alcohol intake as a continuous variable. BMI, body mass index; DHQ, Diet History Questionnaire; HRT, hormone replacement therapy.

Fig 3. Hazard ratios and 95% confidence intervals for the association between categories of average lifetime alcohol intake and overall mortality compared to light drinkers who reported drinking 1–3 alcoholic drinks per week.

Results are adjusted for study centre, race, BMI, randomisation group, smoking status, year of DHQ completion, marital status, educational attainment, family history of cancer (cancer mortality only), hormone replacement therapy use (women only), energy intake, red meat intakes per 1,000 kcal, processed meat intakes per 1,000 kcal, coffee intake, fruit and vegetable intake, fibre intake, and calcium intake. BMI, body mass index; DHQ, Diet History Questionnaire.

Fig 4. Hazard ratios and 95% confidence intervals for the association between categories of average lifetime alcohol intake and total cancer risk compared to never drinkers.

Results are adjusted for study centre, race, BMI, randomisation group, smoking status, year of DHQ completion, marital status, educational attainment, family history of cancer (risk of cancer or death only), HRT use (women only), energy intake, red meat intakes per 1,000 kcal, processed meat intakes per 1,000 kcal, coffee intake, fruit and vegetable intake, fibre intake, and calcium intake. BMI, body mass index; DHQ, Diet History Questionnaire; HRT, hormone replacement therapy.

Fig 5. Hazard ratios and 95% confidence intervals for the association between categories of average lifetime alcohol intake and combined risk of cancer or death compared to light drinkers who reported drinking 1–3 alcoholic drinks per week.

Results are adjusted for study centre, race, BMI, randomisation group, smoking status, year of DHQ completion, marital status, educational attainment, family history of cancer (cancer mortality only), hormone replacement therapy use (women only), energy intake, red meat intakes per 1,000 kcal, processed meat intakes per 1,000 kcal, coffee intake, fruit and vegetable intake, fibre intake, and calcium intake. BMI, body mass index; DHQ, Diet History Questionnaire.