Erikka Cronin

Ph.D., M.P.H.

Erikka Loftfield Cronin

Investigator

PLCO (Learn more about this study)

PLCO-1932

Jun 2, 2025

Investigation of lifetime alcohol drinking with cancer and mortality risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Heavy alcohol drinking in adulthood has been associated with higher risk of certain cancers and mortality, but research on associations of lifetime alcohol drinking, particularly at low to moderate levels, with cancer and mortality risk is limited. A prior study in PLCO, with follow-up through 2009, by Kunzmann et al observed a J-shape between lifetime alcohol intake and mortality. Additionally, they found a borderline association between light to moderate lifetime drinking and breast cancer risk but had limited statistical power to detect associations with specific causes of death and other cancer types.

Our objective is to estimate the association of average lifetime alcohol drinking and increasing/decreasing alcohol consumption from early to later adulthood with risk of a first primary cancer and mortality with extended follow-up for mortality and cancer outcomes.

In PLCO, lifetime alcohol use has been estimated using the DHQ. Participants were asked about frequency of consumption of beer (12-ounce bottle or can), wine (5-ounce glass), and liquor (1.5 ounce shot including mixed drinks) during four pre-defined age ranges (18-24, 25-39, 40-54, and ≥55 years) using ten pre-defined frequency categories (never, 1 drink/month or fewer, 2-3 drinks/month, 1-2 drinks/week, 3-4 drinks/week, 5-6 drinks/week, 1 drink/day, 2-3 drinks/day, 4-5 drinks/day, and 6 or more drinks/day). Participants were also asked about their beer, wine, and liquor consumption in the year prior to DHQ completion. Lifetime alcohol intake was calculated as a weighted average: the sum of the number of alcoholic drinks per day multiplied by the number of years in that age range and then divided by the total number of years from 18 to age at DHQ. We will further categorize participants into the categories based on drinking status and intake levels.

For the first primary cancer analyses, our population will include participants in both the screening and control arms of the study who completed a baseline questionnaire, have a valid DHQ, no history of cancer prior to DHQ, at least 1-year of follow-up, and complete lifetime alcohol data. For mortality analysis, our population will include participants in both the screening and control arms of the study who completed a baseline questionnaire, have a valid DHQ, at least 1-year of follow-up, and complete lifetime alcohol data. Cancer outcomes will be defined using ICD-O-2 site codes and cause of death will be defined using ICD-9 codes. We will use multivariable Cox Proportional Hazards Regression models, adjusted for potential confounding factors, to estimate associations of lifetime alcohol drinking variables with cancer and mortality risk.

1) We will estimate associations of average lifetime alcohol intake and change in alcohol intake with overall and cause-specific mortality. We will consider potential linear and non-linear associations.

2) We will estimate associations of average lifetime alcohol intake and change in alcohol intake with risk of first primary cancer by cancer site/subsite. We will consider potential linear and non-linear associations.

3) We will characterize drinking patterns and study how drinking cessation or reduction impacts mortality and cancer risk.

4) We will explore potential heterogeneity in associations of lifetime alcohol intake and drinking status by cancer histology as well as potential effect modifiers such as smoking.