1 Journal Club Alcohol, Other Drugs, and Health: Current Evidence January–February 2014

2 Featured Article Alcohol consumption and risk of melanoma and non- melanoma skin cancer in the Women’s Health Initiative Kubo JT, et al. Cancer Causes Control. 2014;25(1):1–10.

3 Study Objective To determine whether there is a relationship between alcohol consumption and the risk of developing malignant melanoma (MM) and non- melanoma skin cancer (NMSC) among women.

4 Study Design Prospective cohort of 59,575 white, postmenopausal women (mean age 63.6). Data was collected from the Women's Health Initiative (WHI) Observational Study (OS). Researchers used Cox proportional hazards models and logistic regression techniques to determine risk of MM and NMSC.

5 Assessing Validity of an Article About Harm Are the results valid? What are the results? How can I apply the results to patient care?

6 Are the Results Valid? Did the investigators demonstrate similarity in all known determinants of outcomes? Did they adjust for differences in the analysis? Were exposed patients equally likely to be identified in the two groups? Were the outcomes measured in the same way in the groups being compared? Was follow-up sufficiently complete?

7 Did the investigators demonstrate similarity in all known determinants of outcomes? No, these were adjusted for in the statistical analyses.

8 Did they adjust for differences in the analysis? As skin cancer is rare in other ethnic groups, the investigators excluded non-white participants. Their analysis adjusted for other determinants of skin cancer including age, sun exposure and skin type. There were additional adjustments for education, smoking, BMI, physical activity, having a last medical visit within 1 year of study baseline, insurance status, having a current care provider, history of NMSC, and history of melanoma.

99 Were exposed patients equally likely to be identified in the groups? Yes.

10 Were the outcomes measured in the same way in the groups being compared? Yes. –The two primary outcomes were time to incident melanoma (adjudicated) and occurrence of incident NMSC (self- report) during follow-up.

11 Was follow-up sufficiently complete? Unclear. –There is no data presented to determine whether there was differential follow-up by alcohol exposure category.

12 What are the Results? How strong is the association between exposure and outcomes? How precise is the estimate of the risk?

How strong is the association between exposure and outcome? How precise is the estimate of the risk? Modeling alcohol servings per week as a continuous variable results in a HR of 1.16 (1.06, 1.27) for each seven additional servings for MM and an OR of 1.08 (1.05, 1.11) for each seven additional servings for NMSC. 13

14 How Can I Apply the Results to Patient Care? Were the study patients similar to the patients in my practice? Was the duration of follow-up adequate? What was the magnitude of the risk? Should I attempt to stop the exposure?

15 Were the study patients similar to the patients in my practice? The participants were white post- menopausal women, 50 to 79 years of age.

16 Was the duration of follow-up adequate? Yes –Mean follow-up time was 10.2 years.

17 What was the magnitude of the risk? Participants who consumed ≥7 standard drinks in a week had a higher hazard of MM (hazard ratio [HR], 1.64), and a higher risk of NMSC (odds ratio [OR], 1.23) compared with non-drinkers. Compared with non-drinkers, a preference for either white wine or liquor was associated with an increased hazard of MM (white wine [HR, 1.52]; liquor [HR, 1.65]), and risk of NMSC (white wine [OR 1.16], liquor [OR 1.26]).

18 Should I attempt to stop the exposure? There are considerable observational epidemiologic data suggesting that alcohol consumption may relate to an increase in the risk of MM and NMSC. As mechanisms are not known, there is still concern that much of this association may relate to residual confounding by ultraviolet sun exposure.