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1 Consumption of alcoholic beverages; evaluation of cancer hazards Robert A Baan PhD The IARC MONOGRAPHS International Agency for Research on Cancer Lyon, France

2 The IARC Monographs The IARC Monographs are an authoritative series of scientific reviews that t identify environmental factors that t can increase the risk for human cancer. This cancer-hazard identification is a first step in cancer-risk assessment and cancer prevention Each Monograph includes a critical review by an ad-hoc Working Group of the pertinent scientific literature, and an evaluation of the weight of the evidence that the agent can increase cancer risks to humans

3 The IARC Monographs The WHO encyclopaedia of carcinogens The IARC Monographs evaluate Chemical agents and complex mixtures Occupational exposures Physical agents, biological agents Personal habits and household exposures More than 900 agents have been evaluated 106 are carcinogenic to humans (Group 1) 59 are probably carcinogenic to humans (Group 2A) 248 are possibly carcinogenic to humans (Group 2B) Dr Lorenzo Tomatis ( ) Founder of the IARC Monographs National and international health agencies use the Monographs as a source of scientific information on known or suspected carcinogens and as scientific support for their actions to prevent exposure to these agents

4 The IARC Monographs IARC Monographs classification (default) of agents on the basis of the strength of evidence of carcinogenicity to humans and to experimental animals HUMAN Sufficient Limited Inadequate (or lack of data) ANIMAL Sufficient 1 2A 2B Limited 1 2B 3 Inadequate 1 2B 3 (or lack of data)

5 Alcoholic beverage consumption (world-wide) wide) The WHO identified the consumption of alcoholic beverages as one of the top-10 risks for world-wide burden of disease (Ezzatti et al., 2004). In 2002, more than 1.9 billion adults ( 15 years of age) around the world were estimated to be regular consumers of alcoholic beverages, with an average daily consumption of 13 g of ethanol (about one drink). Over the past 40 years, alcoholic beverage consumption has remained ed stable in most regions of the world, except in the western Pacific region predominantly China where it has increased by about five times.

6 Alcoholic beverage consumption (European Union) Alcohol consumption in 2005 in the population (> 15 yrs) of the European Union: 10.9 L pure ethanol (EU27), varying from 6.6 L (Sweden) to 14.8 L (Czech Republic) Harmful and hazardous alcohol consumption is the third largest risk factor for ill health in the EU, causing 195,000 deaths each year and accounting for 12% of male and 2% of female premature mortality Young gpeople p are at risk, as over 10% of female mortality and around 25% of male mortality in the yrs age group is related to hazardous alcohol consumption [From: Alcohol in Europe - A public health perspective, P Anderson & B Baumberg, Institute of Alcohol Studies, UK 2006]

7 Alcoholic beverage consumption (European Union) Brussels, , 2006 COM (2006) 625 final COMMUNICATION FROM THE COMMISSION TO THE COUNCIL, THE EUROPEAN PARLIAMENT, THE EUROPEAN ECONOMIC AND SOCIAL COMMITTEE AND THE COMMITTEE OF THE REGIONS An EU strategy to support Member States in reducing alcohol-related harm [this document does not mention cancer at all]

8 Alcoholic beverage consumption (European Union) Data available in 2006 estimated that alcohol consumption- related deaths and ill health effects in the EU included: 10,000 deaths per year due to road-traffic accidents 27,000 deaths as a result of alcohol-related l l accidents 2,000 homicides 10, suicides 45,000 deaths from liver cirrhosis 50, deaths from cancer (11,000 female breast cancer) 17,000 deaths due to neuro-psychiatric conditions Alcohol l is also linked to 200, episodes of depression, accounting for 2.5 million life-years lost to death and disability y( (Disability-Adjusted Life Years). From: First progress report on the Implementation of the EU alcohol strategy (2009)

9 Volume 44 of the IARC Monographs Alcohol drinking (Working Group meeting, October 1987) ) There is sufficient evidence for the carcinogenicity of alcoholic beverages in humans. The occurrence of malignant tumours of the oral cavity, pharynx, larynx, oesophagus and liver is causally related to the consumption of alcoholic beverages. Alcoholic beverages are carcinogenic to humans (Group 1)

10 IARC Monograph volume 44 (1988): cohort studies Oral cavity relative risk with 95% C.I. Norwegian alcoholics 5.0 ( ) Pharynx Norwegian alcoholics 4.4 ( ) Finnish alcoholics 5.7 ( ) Oral cavity/pharynx yp y Norwegian alcoholics 4.8 ( ) Massachusetts alcoholics 3.3 ( ) US Veterans alcoholics 2.2 ( ) Canadian alcoholics 4.2 ( )

11 IARC Monograph volume 44 (1988): case control studies Cancer risk depends on the amount of alcohol consumed Tongue, gum, floor of mouth, buccal mucosa France, 759 men 0-39 g*/day ( ) ( ) > ( ) * intake of pure ethanol (Brugère et al., 1986)

12 IARC Monograph volume 96 (2010) The Working Group reviewed epidemiological studies on the possible association between alcohol consumption and cancer at 27 anatomical sites. Regular alcohol consumption is associated with an increased risk for cancers of the oral cavity, pharynx, larynx, and oesophagus. Daily consumption of around 50 g of alcohol increases the risk for these cancers by two to three times, compared with the risk in nondrinkers.

13 IARC Monograph volume 96 (2010) There is strong evidence that the consumption of alcohol is an independent risk factor for primary liver cancer. Cirrhosis and other liver diseases often occur before the cancer becomes manifest and patients with these disorders generally reduce their alcohol intake. Therefore, the effect of alcohol consumption on the risk for liver cancer is difficult to accurately quantify.

14 IARC Monograph volume 96 (2010) In more than 100 epidemiological studies an increased risk was found for female breast cancer with increasing i alcohol intake. A pooled analysis of 53 studies on more than women with and without breast cancer showed that daily consumption of about 50 g of alcohol is associated with a relative risk of about 1.5 (95% C.I., ), compared with that in non-drinkers. For regular consumption of even 18 g of alcohol per day the relative risk is significantly ifi increased.

15 Moderate alcohol intake and breast-cancer risk (Hamajima et al, 2002)

16 IARC Monograph volume 96 (2010) The association between alcohol consumption and colorectal cancer has been reported in more than 50 prospective and case control studies. Pooled results from eight cohort studies and data from recent meta-analyses provide evidence for an increased relative risk of about 1.4 for colorectal cancer with regular consumption of about 50 g of alcohol per day, compared with that in non-drinkers. This risk seems to be similar for colon cancer and for rectal cancer.

17 IARC Monograph volume 96 (2010) The Working Group confirmed the previous conclusion (Volume 44, 1988) that cancers of the oral cavity, pharynx, larynx, esophagus and liver are causally related to the consumption of alcoholic beverages. In addition, there is sufficient evidence to conclude that breast cancer in women and colorectal l cancer also belong in this list. Overall evaluations: Alcoholic beverages are carcinogenic to humans Ethanol in alcoholic beverages is carcinogenic to humans

18 IARC Monograph volume 100E (in prep.) The metabolism of ethanol (alcohol) involves the action of The metabolism of ethanol (alcohol) involves the action of two enzymes, ADH and ALDH:

19 IARC Monograph volume 100E (in prep.) The variant allele ALDH*2 encodes an inactive subunit of the enzyme ALDH. It is highly prevalent in certain eastern- Asian populations p (28 45%), but rare in other groups. Homozygous carriers of this allele (ALDH*2/*2) are natural abstainers or infrequent drinkers, because the enzyme deficiency would cause a strong facial flushing response, physical discomfort, and severe toxic reactions.

20 IARC Monograph volume 100E (in prep.) In heterozygous carriers (ALDH*1/*2 2, with about 10% residual ALDH activity) these acute adverse effects are less severe, but when they consume alcohol these persons are at high risk for several alcohol-related aerodigestive cancers. For oesophageal cancer the relative risk may be as high as 12 for the ALDH*1/*2 genotype, compared with ALDH*1/*1 carriers, who produce normal ALDH.

21 IARC Monograph volume 100E (in prep.) Overall evaluations (Group 1): Alcoholic beverages are carcinogenic to humans Cancer sites: oral cavity, pharynx, larynx, esophagus, liver, female breast, colorectum Ethanol in alcoholic beverages is carcinogenic to humans Acetaldehyde associated with alcohol drinking is carcinogenic to humans

22 Combined effect of alcohol drinking and smoking Alcohol intake (drinks/week) < >56 Smoking habit (cigarettes/day) Never > Odd s ratios for laryngeal cancer (Talamini et al 2005)

23 The IARC Monographs Acknowledgements The IARC Monographs receive financial support from - U.S. National Cancer Institute (since 1982) - European Commission, DG for Employment, Social Affairs and Equal Opportunities (since 1986) -U.S. National Institute of Environmental Health Sciences (since 1992) - U.S. Environmental Protection Agency (since 2001)

24 The IARC Monographs team Merci à toutes et à tous!

25

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