The Relationship between Dietary Factors, Meat Consumption, Heterocyclic amines, Benzo[α]

463 Pages·2009·4.57 MB·English

The Relationship between Dietary Factors, Meat Consumption,
Heterocyclic amines, Benzo[α]pyrene, Meat-derived Mutagenic
activity and Colorectal Cancer in Western Australia

Seyed Mehdi Tabatabaei

MD, Zahedan University of Medical Sciences, Iran, 1997

This thesis is presented for the degree of Doctor of Philosophy
Of the University of Western Australia

School of Population Health

2009
Declaration for thesis containing published work and/or work prepared for
publication

II
Dedication

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III
Statement of Contribution
This thesis is the result of work completed by the candidate, Seyed Mehdi Tabatabaei,
who was responsible for development and testing of the WABOHS meat consumption
questionnaire, and modification of the CHARRED database for estimation of meat
compounds (i.e. HCAs, BaP, and meat-derived mutagenic activity). Mr Tabatabaei was
also responsible for the study design, recruitment of participants, data collection, entry
and analysis of all components of the reliability and the trend study and for the cleaning
and analysis of meat data from the WABOHS study, and preparation of draft
manuscripts for publication.
Contributions were made to this thesis by Associate Professor Jane Heyworth, Professor
Matthew Knuiman, and Associate Professor Lin Fritschi who provided guidance
regarding the design of the project, choice of statistical methods, interpretation of
results and writing of this thesis.

…………………………………… ………..………..
Associate Professor Jane Heyworth (principal supervisor) Date
…………………………………… ………..………..
Professor Matthew Knuiman (co-supervisor) Date

…………………………………… ………..………..
Associate Professor Lin Fritschi (co-supervisor) Date

…………………………………… ………..………..
Seyed Mehdi Tabatabaei (PhD candidate) Date

IV
Abstract

Introduction
The role of meat consumption in the development of cancer, including colorectal cancer
(CRC), has been subject of much investigation in recent years. The observation of
geographical variation in CRC incidence and increased CRC risks in populations
consuming high levels of meat prompted researchers to hypothesise a link between meat
and CRC.
An area of particular interest in CRC pathogenesis is the meat-derived compounds such
are heterocyclic amines (HCAs), polycyclic aromatic hydrocarbons (PAHs), and meat-
derived mutagenic activity. Australia is among the countries with high incidence of
CRC and also high levels of per capita meat consumption. Hence, clarifying the
possible link between meat consumption and the risk of CRC in order that this can be
translated into preventive dietary recommendations for the public is important.

Objectives and aims

The objective of this thesis was to examine whether meat consumption is related to risk
of CRC in an Australian population. The term meat consumption in this thesis means
meaures of consumption of red and white meat that incorporate frequency and cooking
method. The following hypotheses were investigated:

1. Increasing intake of meat prepared by methods that involve higher cooking
temperature and time is positively associated with the risk of CRC;
2. Increasing exposure to meat-derived heterocyclic amines (HCAs) is positively
associated with the risk of CRC;
3. Higher levels of exposure to polycyclic aromatic hydrocarbons (PAHs) from
meat consumption is a risk factor for CRC;
4. Exposure to meat-derived mutagens increases the risk of CRC.

The aims and objectives are addressed in this thesis by nine chapters, as well as
supplementary information on questionnaires used to elicit information on meat
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consumption and covariates data and additional information and statistical analyses
relevant to different chapters of the thesis.
Methods
This PhD project was linked to the Western Australian Bowel Health Study
(WABOHS), a population-based case-control study funded by the National Health and
Medical Research Council (NHMRC), which aimed to investigate the environmental
and genetic risk factors for colorectal cancer in the Western Australian population. As
part of the WABOHS study, which was conducted between 2005 and 2007, data
regarding participants’ meat consumption 10 years before recruitment were collected.
The WABOHS meat consumption questionnaire was adapted from a meat-cooking
module developed by the US National Cancer Institute. This module was linked to a
carcinogen database (i.e. CHARRED). The WABOHS meat consumption questionnaire
and accordingly the CHARRED database were modified to include all meat types
commonly eaten in Australia. Meat consumption data in terms of frequency of
consumption, cooking methods, serving size, and level of doneness were collected.
Meat consumption variables were created by taking into account all theses meat
consumption attributes. The modified CHARRED database was used to estimate
exposure to three individual HCAs (i.e. MeIQx, DiMeIQx, PhIP), BaP (as surrogate
exposure to PAHs), and meat derived mutagenic activity. Multiple logistic regression
models were used to investigate the risk of CRC associated with meat consumption and
meat-derived carcinogenic/mutagenic compounds. The fitted models were adjusted for
potential confounding factors identified in the literature.
The development of the WABOHS meat consumption questionnaire included a
reliability study among the target population; 120 healthy volunteers aged 40-79 and
residing in the Western Australia completed two meat consumption questionnaire three
weeks apart that assessed their consumption 10 years ago. Intraclass correlation
coefficients were used to test the reliability of the meat questionnaire. To further
investigate the reliability of the recalled meat consumption from 10 years ago, 100
healthy controls that had completed a meat questionnaire were asked to complete a
second questionnaire, which examined their meat consumption last year. Intrclass
correlation coefficients were calculated for reported meat consumption last year versus
10 years ago. The reliability coefficients from this study were compared to that from the
reliability study.
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Results and conclusions
This study has not found a relationship between meat consumption and colorectal
cancer. This was the case regardless of the meat-related exposure measured. No
relationship was found between CRC and amount of consumption, cooking methods,
HCAs, PAHs nor mutagenic activity. This study focussed upon improving the
measurement of exposure. The WABOHS meat consumption questionnaire was found
to be a reliable instrument for measuring meat consumption and estimating exposure to
meat carcinogens as determined by reliability analysis using interclass correlation
coefficients. However, the extrapolation from questionnaire data to actual exposure to
meat related carcinogens is still an area of concern.
People can distinguish between recalled past (i.e. 10 years ago) and recent (i.e. last year)
meat consumption. When investigating the role of meat in health outcomes, remote
dietary recall, which is more relevant to the study of chronic disease including cancer
than current diet, is more desirable.
There is a scope for more investigation into the role of meat in colorectal cancer
pathogenesis by improving the methods of past intake coupled with development of
biomarkers of long-terms exposure to meat compounds. In the epidemiological studies
of meat and CRC, taking into account polymorphism in genes coding for the enzymes,
which are thought to be involved in metabolic activation or detoxification of meat-
derived compounds, would further improve exposure measurement.

VII
Table of Contents
DECLARATION FOR THESIS CONTAINING PUBLISHED WORK AND/OR WORK
PREPARED FOR PUBLICATION.........................................................................................................II
STATEMENT OF CONTRIBUTION....................................................................................................IV
ABSTRACT...............................................................................................................................................V
TABLE OF TABLES............................................................................................................................XIII
TABLE OF FIGURES..........................................................................................................................XVI
LIST OF ABBREVIATIONS............................................................................................................XVIII
ACKNOWLEDGEMENTS..................................................................................................................XIX
CHAPTER 1 DIET AND COLORECTAL CANCER......................................................................1
1.1 INTRODUCTION..........................................................................................................................1
1.2 STATEMENT OF AIMS..................................................................................................................6
1.3 OUTLINE OF THE THESIS.............................................................................................................6
CHAPTER 2 LITERATURE REVIEW.............................................................................................8
2.1 MEAT CONSUMPTION.................................................................................................................8
2.1.1 Definition and sources..........................................................................................................8
2.1.2 Meat composition.................................................................................................................8
2.1.3 Meat consumption patterns..................................................................................................9
2.1.4 Epidemiology of meat consumption and cancer risk..........................................................12
2.1.5 Meat consumption measurements.......................................................................................12
2.1.6 Epidemiological studies of meat and CRC.........................................................................15
2.1.7 Conclusion..........................................................................................................................61
2.2 MECHANISMS FOR MEAT CARCINOGENICITY/MUTAGENICITY..................................................63
2.2.1 Oxidative damages due to meat components......................................................................63
2.2.2 Formation of carcinogens/mutagens in cooked meat.........................................................65
2.2.3 Induction of the formation of endogenous carcinogens (NOCs)........................................66
2.2.4 Measurement of mutagenic activity of potential carcinogens............................................68
2.2.5 Factors affecting the formation of mutagenic activity in cooked meat...............................68
2.2.6 Human exposure to mutagenic activity based on meat consumption.................................71
2.2.7 Mutagenic activity of meat-derived compounds (HCAs, PAHs, and NOCs)......................73
2.2.8 Meat-derived mutagenic activity and CRC........................................................................75
2.3 HETEROCYCLIC AMINES...........................................................................................................79
2.3.1 Classification, structural features, and chemical properties..............................................79
2.3.2 Human exposure to HCAs..................................................................................................81
2.3.3 Factors affecting HCA formation in meat..........................................................................85
2.3.4 Metabolism of HCAs..........................................................................................................90
2.3.5 Mutagenicity and genotoxicity of HCAs.............................................................................91
2.3.6 Modulation of the HCA-induced genotoxicity....................................................................92
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2.3.7 Studies of HCA-induced cancers in experimental animals.................................................93
2.3.8 Assessment of exposure to HCAs........................................................................................94
2.3.9 Human colorectal cancer studies.......................................................................................99
2.3.10 Sources of inconsistency in the epidemiological studies of HCAs and CRC...............108
2.3.11 Conclusion...................................................................................................................111
2.4 POLYCYCLIC AROMATIC HYDROCARBONS (PAHS)...............................................................112
2.4.1 Classification, structure and chemical properties............................................................112
2.4.2 Human exposure to PAHs................................................................................................113
2.4.3 Metabolism of PAHs.........................................................................................................126
2.4.4 Mutagenicity and genotoxicity of PAHs...........................................................................126
2.4.5 Assessment of exposure to PAHs......................................................................................129
2.4.6 Biomarkers of human exposure to PAHs..........................................................................130
2.4.7 Human colorectal cancer studies.....................................................................................131
2.5 AIMS & HYPOTHESES OF THESIS............................................................................................137
CHAPTER 3 METHODS.................................................................................................................138
3.1 INTRODUCTION......................................................................................................................138
3.2 WABOHS STUDY..................................................................................................................138
3.2.1 Study population...............................................................................................................138
3.2.2 Data collection overview..................................................................................................141
3.2.3 Data cleaning, processing and entry................................................................................145
3.3 PHD PROJECT STUDY SYNOPSIS..............................................................................................147
3.3.1 Study population...............................................................................................................147
3.3.2 Management of Meat data................................................................................................148
3.3.3 Investigation of relationship between meat exposures and CRC......................................149
CHAPTER 4 DEVELOPMENT OF WABOHS MEAT CONSUMPTION
QUESTIONNAIRE……………………………………………………………………………………..150
4.1 INTRODUCTION......................................................................................................................150
4.2 THE NCI MEAT-COOKING MODULE QUESTIONNAIRE..............................................................151
4.3 CHARRED CARCINOGEN DATABASE....................................................................................152
4.3.1 Database file....................................................................................................................152
4.3.2 Input data.........................................................................................................................153
4.4 MODIFICATION OF CHARRED DATABASE............................................................................155
4.4.1 Mutagen data for intermediate levels of doneness...........................................................155
4.4.2 Fish mutagen data............................................................................................................156
4.4.3 Lamb/mutton mutagen data..............................................................................................165
4.5 WABOHS MEAT QUESTIONNAIRE- PILOT STUDIES................................................................168
4.6 THE FINAL VERSION OF WABOHS MEAT QUESTIONNAIRE....................................................174
4.7 DATA MANAGEMENT FOR WABOHS MEAT QUESTIONNAIRE................................................175
4.8 TEST RE-TEST RELIABILITY STUDY.........................................................................................177
4.8.1 Introduction......................................................................................................................177
4.8.2 Materials and methods.....................................................................................................177
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4.8.3 Results..............................................................................................................................181
4.8.4 Discussion- Reliability Study............................................................................................189
4.9 THE TREND STUDY.................................................................................................................191
4.9.1 Introduction......................................................................................................................191
4.9.2 Subjects and methods.......................................................................................................192
4.9.3 Results..............................................................................................................................194
4.9.4 Discussion- Trend Study...................................................................................................205
CHAPTER 5 MEAT CONSUMPTION, COOKING PRACTICES, AND THE RISK OF
COLORECTAL CANCER...................................................................................................................207
5.1 INTRODUCTION......................................................................................................................207
5.2 SUBJECTS AND METHODS.......................................................................................................208
5.2.1 Study population...............................................................................................................208
5.2.2 Dietary assessment...........................................................................................................209
5.2.3 Statistical analysis............................................................................................................210
5.3 RESULTS................................................................................................................................212
5.4 DISCUSSION...........................................................................................................................220
CHAPTER 6 MEAT-DERIVED HETEROCYCLIC AMINES AND THE RISK OF
COLORECTAL CANCER...................................................................................................................224
6.1 INTRODUCTION......................................................................................................................224
6.2 SUBJECTS AND METHODS.......................................................................................................225
6.2.1 Study population...............................................................................................................225
6.2.2 Dietary assessment...........................................................................................................225
6.2.3 Statistical analysis............................................................................................................226
6.3 RESULTS................................................................................................................................228
6.4 DISCUSSION...........................................................................................................................237
CHAPTER 7 MEAT-DERIVED BENZO[A]PYRENE AND THE RISK OF COLORECTAL
CANCER …………................................................................................................................................242
7.1 INTRODUCTION......................................................................................................................242
7.2 SUBJECTS AND METHODS.......................................................................................................243
7.2.1 Study population...............................................................................................................243
7.2.2 Dietary assessment...........................................................................................................244
7.2.3 Statistical analysis............................................................................................................244
7.3 RESULTS................................................................................................................................246
7.4 DISCUSSION...........................................................................................................................250
CHAPTER 8 MEAT-DERIVED MUTAGENIC ACTIVITY, MUTAGEN INDICES, AND THE
RISK OF COLORECTAL CANCER..................................................................................................253
8.1 INTRODUCTION......................................................................................................................253
8.2 SUBJECTS AND METHODS.......................................................................................................255
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