Committee on National Alcohol Policy and Action 6th Meeting 27-28 January 2010 Alcohol and Cancer Dirk W. Lachenmeier Chemisches und Veterinär- Untersuchungsamt Karlsruhe
Overview Summary of alcohol-related evaluations of the WHO International Agency for Research on Cancer (IARC) Mechanism for alcohol-associated carcinogenicity Quantitative data on alcohol-attributable cancer risk Policy implications
Alcohol-related evaluations of the WHO International Agency for Research on Cancer (IARC)
IARC Monographs Evaluation Process Cancer in humans Sufficient evidence Limited evidence Inadequate evidence Evidence suggesting lack of carcinogenicity Cancer in experimental animals Sufficient evidence Limited evidence Inadequate evidence Evidence suggesting lack of carcinogenicity Mechanistic and other relevant data Mechanistic data weak, moderate, or strong? Mechanism likely to be operative in humans? Overall evaluation Group 1 Group 2A Group 2B Group 3 Group 4 Carcinogenic to humans Probably carcinogenic to humans Possibly carcinogenic to humans Not classifiable as to its carcinogenicity to humans Probably not carcinogenic to humans
IARC Evaluations Cancer in humans Sufficient Limited Inadequate Sufficient Cancer in experimental animals Limited Inadequate Group 1 Group 1 Group 1 Group 2A Group 2B Group 2B Group 2B Group 3 Group 3 Group 1 Carcinogenic to humans 1: Ethanol, Acetaldehyde, Benzene Group 2A Probably carcinogenic to humans Group 2B Possibly carcinogenic to humans 2A: Acrylamide, Ethyl carbamate 2B: Ochratoxin, Pb, Furan Group 3 Not classifiable 3: Patulin, Nivalenol Group 4 Probably not carcinogenic to humans
Timeline of Alcohol-Related IARC Evaluations 1987 (Suppl. 7) 1988 (Vol. 44) 1999 (Vol. 71) 2007 (Vol. 96) 2009 (Vol. 100) Alcoholic beverages Group 1 Sites: oral cavity, pharynx, larynx, oesophagus and liver Group 1 Plus: colo-rectum and female breast Group 1 Plus: Pancreas (limited evidence) Ethanol in alcoholic bevereages (no evaluation, mechanism unclear) Group 1 Group 1 Acetaldehyde associated with alcohol consumption Group 2B (general evaluation) Group 2B (general evaluation) Group 1 Sites: Oesophagus, head and neck Ethyl carbamate (common contaminant in alcohol) Group 2B Group 2A
Summary of IARC evaluation There is sufficient evidence in humans for the carcinogenicity of alcoholic beverages. The occurence of malignant tumours of the oral cavity, pharynx, larynx, oesophagus, liver, female breast and colorectum is causally related to the consumption of alcoholic beverages. There is evidence suggesting lack of carcinogenicity in humans for alcoholic beverages and cancer of kidney and non-hodgkin lymphoma. Limited evidence for pancreas. There is substantial mechanistic evidence in humans with aldehyde dehydrogenase deficiency that acetaldehyde derived from the metabolism of ethanol in alcoholic beverages contributes to the causation of malignant oesophageal tumours. There is sufficient evidence in experimental animals for the carcinogenicity of ethanol. There is sufficient evidence in experimental animals for the carcinogenicity of acetaldehyde. Overall evaluation: Alcoholic beverages are carcinogenic to humans (Group 1). Ethanol in alcoholic beverages is carcinogenic to humans (Group 1). Acetaldehyde associated with alcohol consumption is carcinogenic to humans (Group 1).
Mechanism for alcohol-associated carcinogenicity
Two mechanisms for alcoholrelated carcinogenesis Ethanol Alcoholic beverages Acetaldehyde Alcohol dehydrogenase (ADH) DNA-Adducts Directly contained acetaldehyde and ethyl carbamate 1. Major mechanism: Ethanol and acetaldehyde from metabolism CANCER 2. Minor mechanism: Additive risk from carcinogens directly contained in the beverages
Ethanol metabolism and carcinogenesis Seitz&Stickel, Nat. Rev. Cancer 2007, 7, 599
Mechanisms of acetaldehyde-related carcinogenesis - DNA Adducts - Interstrand Crosslinks - DNA-Protein Crosslinks - Sister Chromatid Exchanges Seitz&Stickel, Nat. Rev. Cancer 2007, 7, 599
Mechanism of carcinogenesis caused by ethanol, acetaldehyde and ethyl carbamate Ethyl carbamate VC- Epoxid Seitz&Stickel, Nat. Rev. Cancer 2007, 7, 599
Dose-Response for Breast Cancer Relative Risk Worldwide evaluation: 58.515 women with breast cancer and 95.067 controls Usual linear risk relationship between average volume of alcohol consumption and cancer risk Source: Hamajima et al. (2002) BJC 87, 1234 Alcohol consumption [g/day] (number of drinks)
What happens to people, if alcohol consumption is stopped or reduced? Meta-analysis of epidemiological literature by Rehm et al. (Int J Cancer 121, 1132-1137, 2007) 13 epidemiological studies including over 5,000 cases indentified about the effects of drinking cessation on the risk for head and neck and oesophagus cancers. Stopping drinking indeed reduced the cancer risks but it took 15-20 years, before the risks were as low as for lifetime abstainers.
Effect of drinking cessation on oesophageal cancer risk by duration 1.20 1.00 0.80 0.60 0.40 0.20 0.00 0.00 5.00 10.00 15.00 20.00 Risk of oesophageal cancer significantly increased within the first 2 years following cessation and was 2.5 times higher than that of current drinkers. Following this, the risk started decreasing rapidly and reached the risk of never drinkers after more than 15 years of abstention. In total 63% of risk reduction was observed after 15 years of quitting drinking compared to current drinkers. Rehm et al. Int J Cancer 121, 1132-1137 (2007)
Quantitative data on alcoholattributable cancer
Alcohol- attributable Mortality DEATH Disease Category EUR A M W T M% W% Maternal and perinatal conditions (low birth weight) 52 38 90 0,0% 0,1% Cancer 37.940 23.393 61.332 30,0% 41,4% Diabetes mellitus 0 0 0 0,0% 0,0% Neuropsychiatric disorders 12.917 4.141 17.058 10,2% 7,3% Cardiovascular diseases 11.953 5.386 17.339 9,5% 9,5% Cirrhosis of the liver 31.063 12.242 43.306 24,6% 21,7% Unintentional injuries 25.040 9.133 34.173 19,8% 16,2% Intentional injuries 7.384 2.105 9.489 5,8% 3,7% Total 'detrimental effects' attributable to alcohol 126.349 56.438 182.787 100,0% 100,0% Diabetes mellitus -3.580-3.305-6.885 6,2% 3,2% Cardiovascular diseases -53.733-98.496-152.229 93,8% 96,8% Total 'beneficial effects' attributable to alcohol -57.313-101.801-159.113 100,0% 100,0% All alcohol-attributable net death 69.037-45.363 23.674 All deaths 1.962.097 2.004.057 3.966.154 Percentage of all net deaths attributable to alcohol 3,5% -2,3% 0,6% Rehm, J., Mathers, C., Popova, S., Thavorncharoensap, M., Teerawattananon, Y., Patra, J. (2009): Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders. Lancet 373: 2223-2233. WHO. (2009): Global Health Risks. Mortality and burden of disease attributable to selected major risks. Geneva, Switzerland: WHO.
Net-effect of alcohol From: Alkohol in Europa, http://ec.europa.eu/health-eu/news_alcoholineurope_en.htm
Alcohol- attributable DALYs DALY Disease Category EUR A M W T M% W% Maternal and perinatal conditions (low birth weight) 2.394 1.878 4.272 0,1% 0,2% Cancer 375.454 236.704 612.158 12,0% 23,4% Diabetes mellitus 0 0 0 0,0% 0,0% Neuropsychiatric disorders 1.469.490 403.034 1.872.524 46,8% 39,8% Cardiovascular diseases 109.274 22.175 131.450 3,5% 2,2% Cirrhosis of the liver 473.422 191.462 664.883 15,1% 18,9% Unintentional injuries 553.495 115.108 668.604 17,6% 11,4% Intentional injuries 156.634 41.550 198.184 5,0% 4,1% Total 'detrimental effects' attributable to alcohol 3.140.164 1.011.911 4.152.074 100,0% 100,0% Diabetes mellitus -109.545-42.530-152.076 24,3% 9,8% Cardiovascular diseases -341.394-390.435-731.829 75,7% 90,2% Total 'beneficial effects' attributable to alcohol -450.940-432.965-883.905 100,0% 100,0% All alcohol-attributable net DALY 2.689.224 578.946 3.268.170 All DALYs 26.813.110 24.625.031 51.438.141 Percentage of all net DALYs attributable to alcohol 10,0% 2,4% 6,4% Rehm, J., Mathers, C., Popova, S., Thavorncharoensap, M., Teerawattananon, Y., Patra, J. (2009): Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders. Lancet 373: 2223-2233. WHO. (2009): Global Health Risks. Mortality and burden of disease attributable to selected major risks. Geneva, Switzerland: WHO.
Policy implications
Policy implications to reduce alcohol-related cancers Ethanol Alcoholic beverages Acetaldehyde Alcohol dehydrogenase (ADH) DNA-Adducts Directly contained Acetaldehyde and ethyl carbamate 1. Major mechanism (ethanol): General policy measures to reduce alcohol consumption CANCER 2. Minor mechanism: Improve alcohol quality, introduce maximum limits for contaminants into EU law
What about unrecorded alcohol? Unrecorded is an overview category for any kind of alcohol that is not taxed as beverage alcohol or registered in the jurisdiction where it is consumed Estimation for 2002: 30% of global alcohol is unrecorded (in EU generally lower, but with a gradient being highest in the Baltic countries) The FP7 AMPHORA project currently tests unrecorded alcohol for quality including carcinogenic contaminants First result: High concentrations of ethyl carbamate in certain unrecorded fruit spirits in Hungary, Poland & Romania (but also in legal fruit spirits; ethyl carbamate in alcohol is seen as health risk by JECFA/EFSA) Special policy measures required for unrecorded alcohol
Warning Labels?
Conclusions Alcoholic beverages are carcinogenic to humans (IARC Group 1). Linear dose-response relationship between volume of alcohol consumption and cancer risk No clear-cut threshold for drinking without cancer risk The development of cancer lags behind for 2-15 years, even after cessation of drinking Research is needed about the contribution of the different mechanisms (ethanol, acetaldehyde, ethyl carbamate) to cancer risk Contamination of alcoholic beverages with carcinogens is avoidable and should be subjected to improved regulatory control (EU-wide maximum limits needed) Policy measures should also include unrecorded alcohol, which might be especially prone to contamination with carcinogens
Thanks for your attention Chemisches und Veterinär- Untersuchungsamt Karlsruhe E-Mail: Lachenmeier@web.de Thanks to: Robert Baan, IARC, for slides on IARC evaluation process Jürgen Rehm, CAMH, Toronto, for quantitative data on cancer burden and slides about drinking cessation
This paper was produced for a meeting organized by Health & Consumers DG and represents the views of its author on the subject. These views have not been adopted or in any way approved by the Commission and should not be relied upon as a statement of the Commission's or Health & Consumers DG's views. The European Commission does not guarantee the accuracy of the data included in this paper, nor does it accept responsibility for any use made thereof.