Quantitative Estimation and Prediction of Human Cancer Risks

by S. Moolgavkar; D. Krewski; L. Zeise; E. Cardis; H. Møller

• ISBN13: 9789283221319
• ISBN10: 9283221311
• Edition: 1st
• Format: Paperback
• Copyright: 1999-08-12
• Publisher: STYLUS PUBLISHING LLC

Summary

This volume assesses formal methods for the quantitative estimation and prediction of human cancer risks. Quantitative estimates of cancer risk can be expressed in different ways. In some cases estimates of risk under conditions prevailing in the original data are of primary interest; in others predictions of risk under other conditions are required. Estimates of risk may be based on empirical models that provide a reasonable description of the available data or on models developed on the basis of plausible assumptions about the mechanisms of carcinogenesis. Throughout this volume established scientific principles of carcinogenesis are used to support methods proposed for the quantitative estimation and prediction of risk.

Table of Contents

Foreword	xi
Contributors	xii
Acknowledgements	xiii
Quantitative estimation and prediction of human cancer risk: its history and role in cancer prevention	1	(10)
A.J. McMichael
A. Woodward
Introduction	1	(1)
Historical background	2	(1)
Definitions of terms and concepts	3	(2)
Regulation and control of cancer risks	5	(2)
Risk prediction	7	(1)
Conclusions	8	(3)
References	9	(2)
Quantitative estimation and prediction of cancer risk: review of existing activities	11	(50)
L. Zeise
E. Cardis
K. Hemminki
M. Schwarz
Introduction	11	(1)
QEP by international bodies using standardized approaches	12	(6)
World Health Organization	12	(1)
Drinking-water	12	(1)
Ambient air	13	(1)
Food residues and additives	14	(1)
General environmental evalutions	15	(1)
Developments in the practice of QEP at WHO	16	(1)
International bodies that assess radiation risks	16	(1)
Other international bodies	17	(1)
QEP by national institutions using standardized approaches	18	(7)
Netherlands	18	(1)
USA	19	(1)
Default risk prediction	20	(1)
Use of QEPs	21	(1)
Canada	22	(2)
Norway	24	(1)
United Kingdom	24	(1)
Germany	25	(1)
Denmark	25	(1)
Standard approaches to QEP for carcinogens	25	(3)
Attempts to improve QEP	28	(12)
``Biologically based'' approaches	28	(1)
Integrated modelling of physiology, pharmacokinetics, pharmacodynamics and cell dynamics: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)	28	(1)
Mechanistic modelling assuming cancer induced by chronic irritation: saccharin	29	(1)
Use of information on DNA cross-links as a measure of dose: formaldehyde	30	(1)
Uncertainty and variability analysis in PBPK models: methylene chloride and perchloroethylene	30	(3)
Meta-analyses of epidemiological data: ionizing radiation and environmental tobacco smoke	33	(1)
Ionizing radiation	33	(1)
Environmental tobacco smoke	34	(1)
Experimental and epidemiological efforts to improve estimates of benzene cancer potency	35	(1)
Modelling of benzene pharmacokinetics	36	(1)
Cohort exposure reconstruction and related dose-response evaluations	37	(1)
Predictions of cancer potency without cancer bioassay or epidemiological data	38	(1)
Ethylene cancer potency inferred from metabolite ethylene oxide	38	(1)
Use of toxicity equivalency factors: complex mixtures	39	(1)
Conclusions	40	(21)
References	42	(19)
Principles of the epidemiological approach to QEP	61	(14)
S. Moolgavkar
H. Moller
A. Woodward
Introduction	61	(1)
Measures of disease frequency and measures of effect	62	(2)
Confounding	64	(1)
Types of epidemiological study	64	(4)
Cohort studies	64	(2)
Case-control studies	66	(1)
Ecological studies	67	(1)
Data analysis	68	(1)
Combined and meta-analyses	69	(2)
Conclusions	71	(4)
References	71	(4)
Measurement of exposure and outcome in epidemiological studies used for quantitative estimation and prediction of risk	75	(28)
B. Armstrong
P. Boffetta
Introduction	75	(1)
Making the right exposure measurements	76	(3)
Nature of exposure measurements	76	(1)
Measurement of dose	76	(1)
Measurement of variation in exposure with time	77	(2)
Effects of exposure measurement error on QEP	79	(3)
Effect of exposure measurement error on the dose-response relationship	79	(1)
Analytical epidemiological studies	80	(1)
Ecological studies	81	(1)
Measurement error in confounding	81	(1)
Analytical epidemiological studies	81	(1)
Ecological studies	81	(1)
Example of effects of exposure measurement error on QEP	81	(1)
Conclusions	82	(1)
Prevention of exposure measurement error	82	(4)
Quality in the design of measurement instruments	82	(2)
Quality control in making and using measurements	84	(1)
Other factors	85	(1)
Control of the effects of exposure measurement error	86	(4)
Multiple measures of exposure	86	(1)
Adjustment of study results for the effects of measurement error	87	(2)
Control of a covariate related to measurement error	89	(1)
Resources for the control of exposure measurement error	90	(1)
Error in the measurement of outcome	90	(7)
Death from cancer	90	(1)
Incidence of cancer	91	(1)
Preneoplastic lesions	92	(1)
Molecular markers of early carcinogenic effect	92	(1)
Sources, measurement and prevention of error in the measurement of outcome	93	(3)
Effect of error in measurement of outcome on the dose-response relationship	96	(1)
Conclusions	97	(6)
References	97	(6)
Long-and medium-term carcinogenicity studies in animals and short-term genotoxicity tests	103	(28)
V. Feron
M. Schwarz
K. Hemminki
D. Krewski
General principles	103	(1)
Design and analysis of cancer bioassays	104	(10)
Long-term studies	104	(1)
Design and conduct	104	(3)
Statistical analysis	107	(1)
Medium-term studies	108	(1)
Mouse skin	109	(1)
Liver	110	(2)
Other organs	112	(2)
Transgenic animals	114	(2)
Use of biomarkers	116	(1)
Short-term tests	117	(1)
Conclusions	118	(13)
References	119	(12)
Empirical approaches to risk estimation and prediction	131	(48)
D. Krewski
E. Cardis
L. Zeise
V. Feron
Introduction	131	(1)
Modelling epidemiological data	132	(8)
Cohort studies	133	(3)
Case-control studies	136	(1)
Generalized linear models	137	(1)
Choice of model from	137	(2)
Other measures of risk	139	(1)
Modelling toxicological data	140	(5)
Quantal-response models	140	(2)
Models of time to response	142	(3)
Patterns of exposure and risk	145	(3)
Carcinogenic potency	148	(5)
The TD50	148	(2)
Variation in carcinogenic potency	150	(1)
Correlation between TD50 and other measures of toxicity	151	(1)
Numerical ranking systems	152	(1)
Joint exposures and carcinogenic mixtures	153	(5)
Modelling the risk of joint exposures	154	(1)
Theoretical predictions of the risks of joint exposures	155	(1)
Empirical studies of the risks of joint exposures	156	(1)
Modelling joint exposures	157	(1)
Risk prediction	158	(3)
Extrapolation from high to low doses	158	(1)
Interspecies extrapolation	159	(2)
Variability, uncertainty and sensitivity analyses	161	(3)
Sources and characterizations of variability	162	(1)
Sources and characterizations of uncertainty	163	(1)
Sensitivity analysis	164	(1)
Summary and conclusions	164	(15)
References	167	(12)
Mechanisms of carcinogenesis and biologically based models for estimation and prediction of risk	179	(60)
S. Moolgavkar
D. Krewski
M. Schwarz
Introduction	179	(1)
Mechanisms of carcinogenesis	180	(7)
Introduction	180	(1)
Oncogenes and tumour-suppressor genes	180	(2)
Proliferation and terminal differentiation of cells	182	(1)
Action of environmental agents	183	(1)
Metabolic factors	183	(1)
DNA binding	184	(1)
Mutations in critical genes	184	(1)
Cell proliferation	185	(1)
Classification of carcinogenic agents	186	(1)
Interindividual variation	187	(3)
Genetic predisposition	187	(1)
Interindividual and interspecies variation in carcinogen metabolism	187	(2)
Interindividual variation in DNA repair	189	(1)
Interspecies variation	190	(1)
Biologically based dose-response models	190	(17)
Introduction	190	(3)
The Armitage-Doll multistage model	193	(3)
The two-mutation model	196	(2)
The hazard function: analysis of incidence data	198	(1)
Radon and lung cancer in rats	199	(1)
Reanalysis of the Colorado Plateau uranium miners' data	200	(1)
Analysis of intermediate lesions	201	(1)
Rodent hepatocarcinogenesis	202	(2)
Initiation-promotion in mouse skin	204	(1)
Joint analyses of premalignant and malignant lesions	205	(1)
Limitations of biologically based models	205	(1)
Data requirements	206	(1)
Pharmacokinetic modelling	207	(6)
Development of a PBPK model	208	(1)
Mathematical description of a PBPK model	208	(1)
Selection of model compartments.	209	(1)
Determination of physiological, biochemical and metabolic parameters	210	(1)
Physiological parameters	210	(1)
Partition coefficients.	210	(1)
Metabolic parameters.	211	(1)
Tissue dosimetry	211	(1)
Applications	212	(1)
Uncertainty, variability and sensitivity analyses	212	(1)
Summary and conclusions	213	(1)
Receptor-binding models	213	(2)
Summary and conclusions	215	(2)
Appendix
A.1 The Armitage-Doll model	217	(1)
A.2 The two-mutation model	217	(22)
A.2.1 The hazard function	217	(2)
A.2.2 Number and size distribution of intermediate foci	219	(2)
References	221	(18)
Review of specific examples of QEP	239	(66)
E. Cardis
L. Zeise
M. Schwarz
S. Moolgavkar
Introduction	239	(1)
Radon and lung cancer	240	(17)
Introduction	240	(1)
Sources of data	240	(1)
Occupational epidemiological studies	240	(4)
Animal studies	244	(1)
Residential radon studies	244	(3)
Mechanistic studies	247	(1)
Cofactors and effect modifiers	248	(1)
Lung dosimetry	249	(1)
Empirical approach to QEP	249	(1)
BEIR IV	249	(1)
Joint analyses of 11 studies on miners	250	(2)
Mechanistic modelling	252	(4)
Comparison of QEP results	256	(1)
Remaining uncertainties, needs for the future	256	(1)
Aflatoxins and liver cancer	257	(19)
Introduction	257	(1)
Epidemiological studies	257	(1)
Correlation studies	257	(3)
Case-control studies	260	(1)
Cohort studies	260	(4)
Experimental data	264	(1)
Animal bioassay	264	(1)
Pharmacokinetics	264	(1)
DNA-adducts	265	(1)
Target gene	266	(1)
Animal models of aflatoxin and HBV interaction	267	(1)
Review of risk assessments	267	(2)
Assessments based on the correlation studies	269	(1)
Analyses based on the Guangxi, China cohort data	269	(4)
Discussion	273	(1)
Reliability of exposure estimates in epidemiological studies	273	(1)
Impact of hepatitis B virus on aflatoxin risk	273	(1)
Genetically determined differences in human susceptibility	274	(1)
Shape of the dose-response curve	275	(1)
Impact of background exposures	275	(1)
Research needs	275	(1)
2,3,7,8-Tetrachlorodibenzo-para-dioxin (TCDD)	276	(29)
Introduction	276	(1)
Experimental data	276	(1)
Animal bioassay	276	(2)
Pharmacokinetic data	278	(1)
Initiation-promotion studies	278	(1)
Short-term tests	279	(1)
Mechanistic aspects of TCDD action	279	(2)
Epidemiological studies	281	(2)
Risk assessment	283	(1)
Conclusions	284	(1)
References	284	(21)
Future perspectives, unresolved issues and research needs	305	(13)
S. Moolgavkar
A. Woodward
D. Krewski
E. Cardis
L. Zeise
Introduction	305	(1)
An example: the case of dioxin (TCDD)	305	(1)
Future perspective and research needs in epidemiology	306	(5)
Genetic and environmental factors in cancer epidemiology	306	(1)
Exposure/dose assessment	307	(1)
Biomarkers of exposure and surrogate end-points	308	(1)
Interindividual variation in susceptibility to carcinogen exposure	309	(2)
Future perspectives and research needs in toxicological studies	311	(2)
Intermediate lesions	311	(1)
Cell proliferation kinetics	311	(1)
Statistical considerations	312	(1)
Future perspectives and research needs for biologically based models of carcinogenesis	313	(4)
The bioassay	317	(1)
Conclusions	317	(1)
References	318