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

Andrew T Kunzmann, Helen G Coleman, Wen-Yi Huang, Sonja I Berndt, Andrew T Kunzmann, Helen G Coleman, Wen-Yi Huang, Sonja I Berndt

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).

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. STROBE flow diagram of participant…
Fig 1. STROBE flow diagram of participant inclusion.
Fig 2
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…
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…
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…
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.

References

    1. Liang W, Chikritzhs T. The Association between Alcohol Exposure and Self-Reported Health Status: The Effect of Separating Former and Current Drinkers. PLoS ONE. 2013;8(2): 1–5.
    1. Chikritzhs T, Stockwell T, Naimi T, Andreasson S, Dangardt F, Liang W. Has the leaning tower of presumed health benefits from “moderate” alcohol use finally collapsed? Addiction. 2015;110(5): 726–727. doi:
    1. Bell S, Daskalopoulou M, Rapsomaniki E, George J, Britton A, Bobak M, et al. Association between clinically recorded alcohol consumption and initial presentation of 12 cardiovascular diseases: population based cohort study using linked health records. BMJ. 2017;356: j909 doi:
    1. Topiwala A, Allan CL, Valkanova V, Zsoldos E, Filippini N, Sexton C, et al. Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study. BMJ. 2017;357: j2353 doi:
    1. Ferrari P, Licaj I, Muller DC, Kragh Andersen P, Johansson M, Boeing H, et al. Lifetime alcohol use and overall and cause-specific mortality in the European Prospective Investigation into Cancer and nutrition (EPIC) study. BMJ Open. 2014;4(7): e005245 doi:
    1. Jayasekara H, MacInnis RJ, Hodge AM, Hopper JL, Giles GG, Room R, et al. Alcohol consumption for different periods in life, intake pattern over time and all-cause mortality. J Public Health. 2015;37(4): 625–633.
    1. Gage S. Do the new alcohol guidelines help us understand the risks of drinking? 2016 Jan 08 [cited 16 Feb 2017]. In: The Guardian [Internet]. London. Available from:
    1. Jivanda T. A bottle of wine a day is not bad for you and abstaining is worse than drinking, scientist claims. 2014 Apr 19 [cited 16 Feb 2017]. In: The Independent [Internet]. London. Available from:
    1. Schütze M, Boeing H, Pischon T, Rehm J, Kehoe T, Gmel G, et al. Alcohol attributable burden of incidence of cancer in eight European countries based on results from prospective cohort study. BMJ. 2011;342: d1584 doi:
    1. WCRF/AICR. Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective. Washington, DC: AICR; 2007.
    1. Stockwell T, Zhao J, Panwar S, Roemer A, Naimi T, Chikritzhs T. Do “Moderate” Drinkers Have Reduced Mortality Risk? A Systematic Review and Meta-Analysis of Alcohol Consumption and All-Cause Mortality. J Stud Alcohol Drugs. 2016;77(2): 185–198. doi:
    1. Friesema IHM, Zwietering PJ, Veenstra MY, Knottnerus JA, Garretsen HFL, Kester ADM, et al. The Effect of Alcohol Intake on Cardiovascular Disease and Mortality Disappeared After Taking Lifetime Drinking and Covariates Into Account. Alcohol Clin Exp Res. 2008. April;32(4): 645–651. doi:
    1. Jayasekara H, English DR, Room R, MacInnis RJ. Alcohol Consumption Over Time and Risk of Death: A Systematic Review and Meta-Analysis. Am J Epidemiol. 2014. May 1;179(9): 1049–1059. doi:
    1. U.S. Department of Health and Human Services and U.S. Department of Agriculture. 2015–2020 Dietary Guidelines for Americans. Washington, DC; 2015.
    1. Prorok PC, Andriole GL, Bresalier RS, Buys SS, Chia D, Crawford DE, et al. Design of the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial. Control Clin Trials. 2000. December;21(6 Suppl): 273S–309S. doi:
    1. Subar AF, Thompson FE, Kipnis V, Midthune D, Hurwitz P, McNutt S, et al. Comparative Validation of the Block, Willett, and National Cancer Institute Food Frequency Questionnaires: The Eating at America’s Table Study. Am J Epidemiol. 2001. December 15;154(12): 1089–1099.
    1. Bowman SA, Friday JE, Moshfegh AJ. MyPyramid Equivalents Database, 2.0 for USDA Survey Foods, 2003–2004: Documentation and User Guide. Baltimore; 2004.
    1. World Cancer Research Fund. Global status report on alcohol and health 2014. Geneva; 2014.
    1. Thiébaut ACM, Bénichou J. Choice of time-scale in Cox’s model analysis of epidemiologic cohort data: a simulation study. Stat Med. 2004. December 30;23(24): 3803–3820. doi:
    1. Desquilbet L, Mariotti F. Dose-response analyses using restricted cubic spline functions in public health research. Stat Med. 2010;29(9): 1037–1057. doi:
    1. Akaike H. Likelihood of a model and information criteria. J Econom. 1981. May;16(1): 3–14.
    1. Cancer Research UK. How alcohol causes cancer [Internet]. [cited 2017 Feb 16]. Available from:
    1. Department of Health. UK Chief Medical Officers’ Alcohol Guidelines Review: Summary of the proposed new guidelines. 2015;(January 2016):7.
    1. Xi B, Veeranki SP, Zhao M, Ma C, Yinkun Y, Jie M. Relationship of Alcohol Consumption to All-Cause, Cardiovascular, and Cancer-Related Mortality in U.S. Adults. J Am Coll Cardiol. 2017. August 22;70(8): 913–922. doi:
    1. Holmes M V, Dale CE, Zuccolo L, Silverwood RJ, Guo Y, Ye Z, et al. Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data. BMJ. 2014. July 10;349: g4164 doi:
    1. Ruitenberg A, van Swieten JC, Witteman JC, Mehta KM, van Duijn CM, Hofman A, et al. Alcohol consumption and risk of dementia: the Rotterdam Study. Lancet. 2002. January 26;359(9303): 281–286. doi:
    1. Naimi TS, Stockwell T, Zhao J, Xuan Z, Dangardt F, Saitz R, et al. Selection biases in observational studies affect associations between “moderate” alcohol consumption and mortality. Addiction. 2017. February;112(2): 207–214. doi:
    1. Bergmann MM, Rehm J, Klipstein-Grobusch K, Boeing H, Schütze M, Drogan D, et al. The association of pattern of lifetime alcohol use and cause of death in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Int J Epidemiol. 2013;42(6): 1772–1790. doi:
    1. Steenland K, Hu S, Walker J. All-cause and cause-specific mortality by socioeconomic status among employed persons in 27 US states, 1984–1997. Am J Public Health. 2004. June;94(6): 1037–1042.
    1. Lee SJ, Sudore RL, Williams BA, Lindquist K, Chen HL, Covinsky KE. Functional Limitations, Socioeconomic Status, and All-Cause Mortality in Moderate Alcohol Drinkers. J Am Geriatr Soc. 2009. June;57(6): 955–962. doi:
    1. Pinsky P, Miller A, Kramer B, Church T, Reding D, Prorok P, et al. Evidence of a Healthy Volunteer Effect in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Am J Epidemiol. 2007. February 28;165(8): 874–881. doi:

Source: PubMed

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