Outline. Background on the American Institute for Cancer Research (AICR) and Continuous Update Project (CUP)

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1 Alcohol and Cancer: State of the Science Christine L. Sardo Molmenti PhD, MPH, RD AICR Science Analyst Assistant Professor Hofstra-Northwell School of Medicine Northwell Health April 25, 2017

2 Outline Background on the American Institute for Cancer Research (AICR) and Continuous Update Project (CUP) Recommendations for alcohol and cancer prevention Scientific evidence behind the recommendations

3 The World Cancer Research Fund Network American Institute for Cancer Research Washington DC (est. 1982) World Cancer Research Fund UK London (est. 1990) World Cancer Research Fund NL Amsterdam (est.1994) World Cancer Research Fund HK Hong Kong (est.1997) World Cancer Research Fund International (est. 1999) Leads and unifies a network of cancer charities with a global reach, dedicated to the prevention of cancer through diet, weight and physical activity.

4 New Expert Report

5 13 CUP reports so far

6 People involved in the CUP More than 100 scientists 17 countries Team of researchers for the CUP at Imperial College London CUP Panel of independent experts Includes CUP Expert Panel, researchers, peer reviewers, advisers and more

7 Grading the evidence Decreases risk Increases risk Strong evidence Limited evidence Strong evidence Convincing Probable Limited - suggestive Limited no conclusion Substantial effect on risk unlikely Basis for recommendations

8 Grading criteria Predefined requirements for Number and types of studies Quality of exposure and outcome assessment Heterogeneity within and between study types Exclusion of chance, bias or confounding Biological gradient Evidence of mechanisms Size of effect

9 For cancer prevention, don t drink alcohol ALCOHOLIC DRINKS Convincing DECREASES RISK INCREASES RISK Mouth/throat; oesophagus (SCC); liver; colorectum (men); breast (pre & post) Probable Kidney Stomach; colorectum (women) Substantial effect on risk unlikely None identified Alcohol consumption linked to an increased risk of 7 cancers

10 AICR Recommendation If alcoholic drinks are consumed, limit consumption to no more than two drinks a day for men and one drink a day for women

11 Strength of association varies by site Cancer RR per 10g/d Number of cohort studies Oropharynx, larynx, pharynx n/a 2 Oesophagus (squamous cell carcinoma) 1.25 ( ) 6 Colorectum 1.10 ( ) 8 Breast (premenopause) 1.09 ( ) 10 Breast (postmenopause) 1.08 ( ) 25 Liver 1.04 ( ) 14 Stomach 1.02 ( ) 23 Kidney 0.92 ( ) 7

12 Association strongest for cancers of the upper aerodigestive tract Cancer RR per 50g/d Oral cavity, pharynx, larynx, esophagus 4-7 Colorectum 1.5 Breast 1.5 Liver 1.5

13 Esophageal squamous cell carcinoma Steeper increase in risk for lower intakes

14 Esophageal squamous cell carcinoma

15 Synergistic effects of smoking and alcohol Smoking is a significant confounder/effect modifier Risk holds even among non-smokers Meta-analysis (15 studies) found consumption of 4 drinks/d most strongly associated with pharynx but also oropharynx, larynx, esophageal SCC Pooled analysis of case-control studies, heavy alcohol consumption ( 3 drinks/d) associated with oropharynx and larynx cancer Zeka et al, 2003 Hashibe et al, 2007

16 Colorectal cancer 8 (all) cohort studies showed increased risk with increased intake (dose-response relationship) Greater effect in men than women 11% vs 7% increased risk respectively per 10g/d Pooled analysis of >4600 colorectal cancer cases among > participants followed for 6-16 years 41% increased risk for groups that drank the most alcohol Interaction with smoking unclear

17 Breast cancer Dose-response meta-analysis 3 cohort studies, 7 case-control studies 10 g ethanol per day Statistically significant increased risks: All ER+ (12%) All ER- (7 %) ER+, PR+ (11 %) ER+, PR- (15%) Not ER-, PR- Each drink/d associated with 11% increase in postmenopausal breast cancer risk

18 Breast cancer Pooled analysis of 53 studies, >58,000 women with breast cancer (included in IARC 2010 review) Linear dose response association 7.1% increase risk per 10g/d increase in ethanol consumption No effect modification by numerous factors including age at dx, parity, age at first birth, breast feeding, race, country, education, BMI, OC use, menopausal status, FDR with breast cancer High risk women should avoid alcohol Binge drinking specially deleterious in younger women Hamajima et al, 2002

19 Liver cancer (hepatocellular carcinoma) Alcohol is a cause of cirrhosis predisposes to liver cancer Excluded patients with cirrhosis, HBV, HBC, history or alcoholism 14 studies included in dose response analysis 4% increased risk per 10 g/d Meta-analysis of 19 prospective cohort studies 16% increased risk compared to non-drinkers (3 drinks/d) Pooled relative risk among 6 drinks/d = 1.22(1.10, 1.35) Turati et al, 2014

20 Pancreatic cancer Evidence considered limited-suggestive Dose response analyses revealed a suggestion of an increased risk in heavier drinkers (> ~3 drinks/day) ACS CPS-II 1 million US adults, 24 years follow up, 7000 pancreatic cancer deaths 3 drinks/d associated with increased risk of pancreatic cancer death [RR=1.36 (1.13, 1.62) Gapstur et al, 2011

21 Cancer survivors Evidence unclear Pre diagnostic alcohol in take 18 total studies published through 2012 No associations of pre-diagnostic alcohol intake with total mortality or risk of second primary breast cancer Post diagnostic alcohol intake Inconsistent results Not dose related Premenopausal vs postmenopausal Post-menopausal women who consume at least 6/d, 19% higher risk No association found among pre-menopausal women Gapstur, 2017

22 Summary Alcoholic drinks are a cause of cancers of the oral cavity, pharynx, larynx, esophagus, liver, colorectum (men), and breast. Probable cause of stomach cancer and colorectal cancer (women).

23 Recommendation For cancer prevention, it s best not to drink alcohol. If you do, limit alcoholic drinks to two drinks per day for men and one drink per day for women

24 For further information Christine L. Sardo Molmenti, PhD, MPH, RD Science Analyst American Institute for Cancer facebook.com/wcrfint