Alcohol and Cancer: Defining the Exposure and Key Milestones in Establishing the Relationship Susan M. Gapstur, PhD, MPH Vice President, Epidemiology American Cancer Society 1
Disclosure Information SUSAN M. GAPSTUR, PhD, MPH I have no conflicts of interest to disclose.
Outline Defining the exposure. The prevalence of alcohol consumption in the US. The general health effects of alcohol consumption. Historic classification of alcohol as a human carcinogen. Potential biologic mechanisms underlying the causal effects of alcohol in carcinogenesis. Population attributable fractions for alcohol consumption and death from cancers causally associated with alcohol consumption and for cancer deaths overall in the US. Guidelines for alcohol consumption.
Archeologic Evidence Shows Alcohol Produced as Early as 7000 6600 BC in China* Religious, Social Cultural McGovern et al., Proc Natl Acad Sci, 101(51), 17593 8; 2004
Types of Alcoholic Beverages Most Commonly Consumed 12 fl oz Regular Beer 5 fl oz Table Wine 1.5 fl oz shot 80-Proof Spirits 5% alcohol 12 % alcohol 40% alcohol Any drink that contains about 14 grams of pure ethanol. http://rethinkingdrinking.niaaa.nih.gov/whatcountsdrink/whatsastandarddrink.asp
Trends in Per Capita Ethanol Consumption (gallons), United States, 1935 2014 1981 =2.75 gallons 2014 =2.32 gallons https://pubs.niaaa.nih.gov/publications/surveillance104/cons14.htm 6
Trends in Per Capita Ethanol Consumption (gallons) by Beverage Type, United States, 1977 2014. Beer Spirits Wine https://pubs.niaaa.nih.gov/publications/surveillance104/cons14.htm 7
Per Capita Consumption (gallons) of Ethanol by State, United States, 2014 https://pubs.niaaa.nih.gov/publications/surveillance104/cons14.htm 8
WHO Estimates of Health Effects of Alcohol Consumption 5.9% of all deaths 5.1% of disease 60 common alcohol related conditions and 200 conditions in which alcohol is a component cause. Some examples include: Unintentional injuries Burns, falls, motor vehicle crashes Drowning, homicide, suicide Birth defects Depression GI disorders: stomach bleeding, liver and pancreas diseases Sleep disorders Sexually transmitted infection from unsafe sex WHO. 2014. Global Status Report on Alcohol and Health 2014. WHO (Ed.). Geneva: WHO
Early Epidemiologic Evidence that Alcohol Consumption is Associated with Cancer Risk Personal interviews from 7,518 incidence cases of invasive cancer Lifetime use of cigarettes, cigars, pipes, other tobacco, Wine, beer, liquor Education and family income Cases from one site compared to controls from other sites Findings showed that alcohol consumption was associated with cancers of: Oral cavity Larynx Esophagus Colon rectum Breast Thyroid
The IARC Monographs Program Convenes international panel of experts to evaluate carcinogenic risks to humans posed by environmental factors (e.g., chemicals, occupational exposures, physical agents, biological agents, and personal habits). Define exposure Human evidence Animal studies Mechanistic studies
Evaluation of Strength of Evidence for Carcinogenicity, NOT DOSE Group Classification Parameter I* Carcinogenic to humans Sufficient evidence of carcinogenicity in humans and in experimental animals 2A 2B Probably carcinogenic to humans Possibly carcinogenic to humans 3 Agent is not classifiable as to its carcinogenicity to humans 4 Agent is probably not carcinogenic to humans Limited evidence of carcinogenicity in humans and sufficient evidence in experimental animals Limited evidence of carcinogenicity in humans and less than sufficient evidence in experimental animals Inadequate evidence of carcinogenicity in humans and in experimental animals Evidence suggesting lack of carcinogenicity in humans and in experimental animals No. of Agents 120 81 294 505 1 * An agent can be in Group 1 in the absence of sufficient evidence for carcinogenicity in humans if there is sufficient data in experimental animals and strong evidence that the agent act through similar mechanism in humans. 12
1987 2007 2009 IARC Monograph Program: Evaluation of Alcohol and Cancer Volume 46 (1988) Volume 96 (2010) Volume 100E (2012) 13
IARC Finds Evidence is Sufficient (Group 1) that Alcoholic Beverages, Ethanol in Alcoholic Beverages*, and Acetaldehyde are carcinogenic to Humans Type of cancer Alcoholic Beverages Ethanol Acetaldehyde Oral Cavity 1987, 2007, 2009 2009 2009 Pharynx 1987, 2007, 2009 2009 2009 Larynx 1987, 2007, 2009 2009 2009 Esophagus 1987, 2007, 2009 2009 2009 Liver 1987, 2007, 2009 Colorectum 2007, 2009 Female breast 2007, 2009 *2007: Ethanol in alcohol beverages is carcinogenic (but no statement about specific type of cancer). 14
IARC Finds Evidence of Lack of Carcinogenicity (Group 4) for Alcohol with Two Types of Cancer Type of cancer Alcoholic Beverages NHL 2007, 2009 Kidney 2007, 2009 15
Alcohol Metabolism Induced at high amounts Nature Reviews Cancer 7, 599-612 (August 2007)
Alcohol and Cancer: Possible Biologic Mechanisms Alcohol Metabolism Acetaldehyde increases liver cell proliferation Acetaldehyde can lead to DNA adduct formation ROS formation Estrogen and hormones Alcohol increase levels of estrogen. (Breast cancer) Liver cirrhosis Heavy alcohol consumption causes liver cirrhosis which increases liver cancer risk Alcohol and other carcinogens Alcohol can increase absorption of other cancer causing agents in tobacco Effects on absorption and metabolism of other nutrients Alcohol can reduce folate absorption in the gut
Cancer Deaths Attributed to Alcohol Consumption in the U.S. Rothman et al. (1980): 3% of all US cancer deaths in 1974 Doll and Peto (1981): 2% to 4% of US cancer deaths in late 1970s Nelson et al. (2013): 3.2-3.7% of US cancer deaths in 2009 Four estimates two different statistical models two different population-based surveys (i.e., 2009 BRFSS and the 2009 2010 National Alcohol Survey), and alcohol sales data to estimate prevalence of consumption. 18
TOTAL Number (%) US Cancer Deaths Attributed to Alcohol Consumption (2009) ALL CANCER DEATHS Men Women Total N 6,970 to 11,820 7,266 to 13,094 18,178 to 21,284 (%) (2.4-4.0%) (2.7-4.8%) (3.2-3.7%) Nelson DE, et al., Am J Public Health 2013;103;641-48 19
Cancer Deaths Attributed to Alcohol Consumption in the U.S. Men Women Oral cavity & pharynx 27-66% 26-38% Larynx 17-38% 11-22% Esophagus 17-34% 16-21% Colon 4-8% 2-14% Rectum 8-10% 4-15% Liver 11-16% 8-16% Female breast NA 12-18% Nelson DE, et al., Am J Public Health 2013;103;641-48 20
But Is There a Silver Lining? Alcohol and Longevity (1926): Dr. Raymond Pearl reported that drinking alcohol in moderation is associated with greater longevity compared to abstaining or drinking heavily
Deaths per 100,000 Daily Alcohol Intake and All-cause Mortality 1600 1483 1431 Men 1200 1215 1167 1209 1247 1335 800 843 684 666 715 781 784 828 Women 400 0 None <1 1 2 3 4-5 6+ Drinks per Day Thun et al, NEJM 1997
Current Alcohol Drinking & CVD and CHD Mortality Ronksley P E et al. BMJ 2011;342:bmj.d671
Current Alcohol Drinking & Stroke Mortality Meta-incidence analysis 12 studies of hemoragic stroke: RR=1.14 (0.97-1.34) 8 studies of ischemic stroke: RR=0.92 (0.85-1.00) Ronksley P E et al. BMJ 2011;342:bmj.d671
Biologic Effects of Alcohol Consumption on CVD Risk Factors BENEFIT: Moderate consumption Higher levels of HDL cholesterol Improved insulin sensitivity Decreased fibrinogen levels Decreased inflammatory markers (e.g., CRP, IL-6) RISKS: Drinking too much alcohol Increased circulating triglycerides Increases blood pressure Increases risk of heart failure, cardiomyopathy and cardiac arrhythmia
Antsie s Rule (1870) Upper limit of 3 drinks per day (applied only to men). Baldwin AD. AJPH 67(7):679-81;1977
Excess Consumption of Alcohol is One of Many Poor Lifestyle Choices
Alcoholic Beverage Consumption Guidelines No organization recommends that people start drinking if they do not currently drink alcohol! American Cancer Society Guidelines for Cancer Prevention If you do not drink alcohol, do not start drinking. For those who do drink alcoholic beverages limit consumption to no more than 2 drinks per day for men and 1 drink per day for women. American Institute for Cancer Research Limit Alcohol. Even small amounts of alcohol pose some cancer risk, so for lowest risk, AICR recommends not drinking alcohol at all. However, if you do drink alcohol, limit your intake to no more than 2 drinks a day for men and 1 drink a day for women. American Heart Association If you drink alcohol, do so in moderation. This means an average of 1-2 drinks per day for men and 1 drink per day for women. (The American Heart Association cautions people NOT to start drinking... if they do not already drink alcohol).
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