Alcohol consumption and ethyl carbamate

1440 Pages·2011·13.18 MB·English

WORLD HEALTH ORGANIZATION
INTERNATIONAL AGENCY FOR RESEARCH ON CANCER

IARC Monographs on the Evaluation of
Carcinogenic Risks to Humans
VOLUME 96
Alcohol Consumption and
Ethyl Carbamate
LYON, FRANCE
2010

IARC Monographs on the Evaluation of
Carcinogenic Risks to Humans
VOLUME 96
Alcohol Consumption and
Ethyl Carbamate
This publication represents the views and expert opinions
of an IARC Working Group on the
Evaluation of Carcinogenic Risks to Humans,
which met in Lyon,
6–13 February 2007
2010
IARC MONOGRAPHS
In 1969, the International Agency for Research on Cancer (IARC) initiated a programme on the evaluation of the
carcinogenic risk of chemicals to humans involving the production of critically evaluated monographs on individual
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evaluations are regularly updated and are available on the Internet at http://monographs.iarc.fr/.
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Published by the International Agency for Research on Cancer,
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International Agency for Research on Cancer, 2010
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IARC Library Cataloguing in Publication Data
Alcohol consumption and ethyl carbamate/ IARC Working Group on the Evaluation of Carcinogenic
Risks to Humans (2007: Lyon, France)
(IARC monographs on the evaluation of carcinogenic risks to humans; v. 96)
1. Alcoholic Beverages – adverse effects 2. Alcohol Drinking – adverse effects 3. Carcinogens
4. Ethanol – adverse effects 5. Neoplasms – etiology 6. Urethane – adverse effects
7. Urethane – toxicity
I. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans
II. Series
ISBN 978 92 832 1296 6 (NLM Classification: W1)
ISSN 1017-1606
PRINTED IN FRANCE
Cover: Henri de Toulouse-Lautrec (1864-1901) “The Hangover” (Portrait of Suzanne
Valadon), 1888, oil on canvas. Harvard Art Museums/Fogg Art Museum. Bequest from the
Collection of Maurice Wertheim, Class of 1906, 1951.63
Photo: Imaging Department © President and Fellows of Harvard College, reproduced with
permission.
The chemical formulae show the two-step metabolism of ethyl alcohol, mediated by the key
enzymes ADH and ALDH.

Cover design: Roland Dray (IARC)

CONteNtS
NOTE TO THE READER..............................................................................................1
LIST OF PARTICIPANTS..............................................................................................3
PREAMBLE....................................................................................................................7
A. GENERAL PRINCIPLES AND PROCEDURES.....................................................7
1. Background...........................................................................................................7
2. Objective and scope..............................................................................................8
3. Selection of agents for review...............................................................................9
4. Data for the Monographs....................................................................................10
5. Meeting participants...........................................................................................11
6. Working procedures............................................................................................12
B. SCIENTIFIC REVIEW AND EVALUATION........................................................13
1. Exposure data.....................................................................................................14
2. Studies of cancer in humans...............................................................................16
3. Studies of cancer in experimental animals.........................................................20
4. Mechanistic and other relevant data...................................................................23
5. Summary.............................................................................................................27
6. Evaluation and rationale.....................................................................................28
References.........................................................................................................33
GENERAL REMARKS...............................................................................................37
CONSUMPTION OF ALCOHOLIC BEVERAGES ...............................41
1. Exposure Data .................................................. 41
1.1 Types and ethanol contents of alcoholic beverages ....................41
1.2 Production and trade of alcoholic beverages ...........................42
1.3 Trends in consumption ...............................................50
1.4 Sociodemographic determinants of alcoholic beverage consumption ...71
1.5 Non-beverage alcohol consumption ...................................77
1.6 Chemical composition of alcoholic beverages, additives and
contaminants .............................................................79
1.7 Biomarkers, biomonitoring and aspects of survey measurement .......137
1.8 Regulations on alcohol ..............................................140
2. Studies of Cancer in Humans ..................................... 171
Assessment of alcoholic beverage intake in case–control
and cohort studies ............................................. 172
2.1 Description of cohort studies ........................................174
–v–
vi IARC MONOGRAPHS VOLUME 96
2.1.1 Studies in general populations ...............................174
2.1.2 Studies in special populations ................................231
2.2 Cancer of the oral cavity and pharynx. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .237
2.2.1 Cohort studies ...............................................237
2.2.2 Case–control studies .........................................247
2.2.3 Types of alcoholic beverage ..................................275
2.2.4 Joint effects .................................................275
2.2.5 Effect of cessation of alcoholic beverage consumption ........315
2.2.6 Effect of alcoholic beverage consumption in nonsmokers .....315
2.3 Cancer of the larynx .................................................329
2.3.1 Cohort studies ...............................................330
2.3.2 Case–control studies .........................................333
2.3.3 Subsites of the larynx ........................................333
2.3.4 Types of alcoholic beverage ..................................347
2.3.5 Joint effects .................................................349
2.3.6 Effect of cessation of alcoholic beverage consumption ........350
2.3.7 Effect of Alcoholic beverage consumption in nonsmokers .....350
2.4 Cancer of the oesophagus ...........................................351
2.4.1 Cohort studies ...............................................352
2.4.2 Case–control studies .........................................370
2.4.3 Histological types ...........................................370
2.4.4 Type of alcoholic beverage ..................................389
2.4.5 Evidence of a dose–response .................................389
2.4.6 Effect of cessation of alcoholic beverage consumption ........389
2.4.7 Effect modification ..........................................399
2.5 Cancer of the liver ..................................................399
2.5.1 Cohort studies ...............................................404
2.5.2 Case–control studies .........................................404
2.5.3 Meta-analyses ...............................................415
2.5.4 Interaction with hepatitis viral infection ......................415
2.5.5 Interaction with tobacco smoking ............................418
2.6 Breast cancer .......................................................418
2.6.1 Pooled and meta-analyses ....................................418
2.6.2 Additional cohort studies ....................................419
2.6.3 Additional case–control studies ..............................419
2.6.4 Measurements of alcoholic beverage intake. . . . . . . . . . . . . . . . . . .419
2.6.5 Tumour type ................................................463
2.6.6 Types of alcoholic beverage ..................................479
2.6.7 Subgroups of women ........................................479
2.6.8 Male breast cancer ...........................................479
CONTENTS vii
2.7 Cancer of the stomach ...............................................486
2.7.1 Cohort studies ...............................................486
2.7.2 Case–control studies .........................................498
2.7.3 Anatomic subsite and histological type .......................498
2.7.4 Type of alcoholic beverage ..................................535
2.7.5 Effect modification ..........................................535
2.8 Cancers of the colon and/or rectum ..................................542
2.8.1 Cohort studies ...............................................542
2.8.2 Case–control studies .........................................564
2.8.3 Potential confounding .......................................600
2.8.4 Effect modification ..........................................601
2.8.5 Conclusion ..................................................602
2.9 Cancer of the pancreas ..............................................602
2.9.1 Cohort studies ...............................................602
2.9.2 Case–control studies .........................................617
2.10 Cancer of the lung ..................................................617
2.10.1 Total alcoholic beverage consumption ........................632
2.10.2 Histological type ............................................679
2.10.3 Types of alcoholic beverage ..................................679
2.10.4 Studies stratified by tobacco-smoking status ..................700
2.10.5 Studies among nonsmokers ..................................714
2.10.6 Population characteristics ....................................714
2.11 Cancer of the urinary bladder ........................................720
2.12 Cancer of the endometrium ..........................................741
2.12.1 Cohort studies ...............................................741
2.12.2 Case–control studies .........................................741
2.12.3 Evidence of a dose–response .................................761
2.12.4 Types of alcoholic beverage ..................................762
2.12.5 Interactions .................................................762
2.13 Cancer of the ovary .................................................762
2.13.1 Cohort studies ...............................................762
2.13.2 Case–control studies .........................................770
2.13.3 Evidence for a dose–response ................................770
2.13.4 Types of alcoholic beverage ..................................770
2.13.5 Interactions .................................................770
2.14 Cancer of the uterine cervix .........................................787
2.14.1 Cohort studies ...............................................787
2.14.2 Case–control studies .........................................787
2.14.3 Evidence of a dose–response .................................802
2.14.4 Types of alcoholic beverage ..................................802
2.14.5 Interactions .................................................802
viii IARC MONOGRAPHS VOLUME 96
2.15 Cancer of the prostate ...............................................803
2.15.1 Cohort studies ...............................................803
2.15.2 Case–control studies .........................................803
2.15.3 Meta-analysis ...............................................843
2.16 Cancer of the kidney ................................................843
2.16.1 Cohort studies ...............................................843
2.16.2 Case–control studies .........................................849
2.16.3 Evidence of a dose–response .................................849
2.16.4 Type of alcohol ..............................................871
2.16.5 Interactions .................................................871
2.17 Cancers of the lymphatic and haematopoietic system .................871
2.17.1 Cohort studies ...............................................871
2.17.2 Case–control studies .........................................875
2.17.3 Parental exposure and childhood cancers .....................891
2.18 Cancer at other sites. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .907
2.18.1 Testis .......................................................907
2.18.2 Cancer of the brain ..........................................910
2.18.3 Cancer of the thyroid ........................................923
2.18.4 Melanoma ...................................................923
2.18.5 Other female cancers (vulva and vagina) .....................923
3. Studies of Cancer in Experimental Animals ......................... 1001
3.1 Ethanol and alcoholic beverages ....................................1001
3.2 Modifying effects of ethanol on the activity of known carcinogens ...1008
3.3 Acetaldehyde ......................................................1067
4. Mechanistic and Other Relevant Data Relevant ...................... 1079
4.1 Absorption, first-pass metabolism, distribution and excretion ........1079
4.2 Metabolism ........................................................1083
4.3 Genetic susceptibility ..............................................1105
4.4 Modifying effects of ethanol consumption on
metabolism and clearance ...............................................1153
4.5 Major toxic effects .................................................1167
4.6 Reproductive and perinatal toxicity .................................1179
4.7 Genetic and related effects .........................................1183
4.8 Mechanistic considerations .........................................1201
5. Summary of Data Reported ..................................... 1267
5.1 Exposure data ......................................................1267
5.2 Human carcinogenicity data ........................................1268
5.3 Animal carcinogenicity data ........................................1273
5.4 Mechanistic and other relevant data .................................1274
6. Evaluation and Rationale ....................................... 1278