Selected Research Projects
Air Pollution: Short-Term Effects
Particulate air
pollution and daily mortality in Montreal, Quebec, 1984-1993
Granting agency: Health Effects Institute,
PI: Mark Goldberg
Collaborators: JC Bailar III, Robyn Tamblyn, Richard Burnett, Jeffrey Brook, Yvette Bonvalot, Hélène Riberdy.
Abstract: This
submission is in response to the Health Effects Institute’s RFA94-2, Objective
1, that requested applications to develop epidemiologic studies that would
identify populations at higher than average risk from dying because of ambient
exposure to particulates. The present
proposal is designed to investigate cause-specific mortality in relation to
sub-groups of the general population with varying levels of preexisting medical
conditions. Thus, the principal
objectives of the present investigation are 1) to determine whether
concentrations of particulates in the ambient air of Montreal, Quebec were
associated with daily all-cause and cause-specific mortality in the period 1984
to 1993, inclusive and 2) to determine whether there are sub-groups of the
population (individuals with specific health conditions prior to death or those
who were hospitalized at the time of death) with higher than average risks from
particulates.
This study will cover
the Island of Montreal, Quebec (hereafter referred to as
This study will use 10
years of mortality, air pollution, and meteorologic data (1984-93). The ambient air of
Publications:
Goldberg MS. Particulate air pollution and daily mortality. Who is at risk? J
Aerosol Medicine, 1996;9:43-53.
Goldberg
MS, Bailar JC III, Burnett R, Brook J, Tamblyn R,
Bonvalot Y, Ernst P, Flegel KM, Singh R, Valois M-F. Identifying subgroups
of the general population that may be susceptible to short-term increases in
particulate air pollution: A time series
study in
Goldberg
MS, Burnett R, Brook J, Tamblyn R, Bonvalot Y, Singh
R, Valois M-F, Bailar III JC. Cause-specific mortality and exposure to
particulates in
Goldberg
MS, Burnett R, Brook J, Tamblyn R, Flegel K, Ernst
P, Bonvalot Y, Singh R, Valois M-F, Bailar III JC. The
Goldberg
MS, Burnett R, Bailar JC III, Brook J, Bonvalot Y,
Tamblyn R, Singh R, Valois M-F. The association between daily mortality and
short-term effects of ambient air particle pollution in
Goldberg
MS, Burnett R, Bailar JC III, Brook J, Bonvalot Y,
Tamblyn R, Singh R, Valois M-F, Vincent R. The association between daily
mortality and short-term effects of ambient air particle pollution in
Goldberg
MS, Burnett R, Bailar JC III, Tamblyn R, Ernst P,
Flegel K, Brook J, Bonvalot Y, Singh R, Valois M-F, Vincent R. The
identification of persons with cardio-respiratory conditions who are at risk of
dying from the acute effects of ambient air particles. Env Health Perspect 109(Suppl 4):487-494, 2001.
Mark S. Goldberg, Richard T. Burnett, Jeffrey Brook,
John C. Bailar III, Marie-France Valois, Renaud Vincent. Associations between
Daily Cause-specific Mortality and Concentrations of Ground-level Ozone in
Goldberg MS, Burnett RT, Valois M-F*, Flegel K, Bailar III JC, Brook
J, Vincent R, Radon K. Associations between Ambient Air Pollution and Daily
Mortality among Persons with Congestive Heart Failure. Environmental Research, In press.
Kolb
S*, Radon K, Goldberg MS. The
short-term influence of weather on daily mortality in congestive heart failure.
Arch Environ and Occup Health 2007;62(4):169-76.
Goldberg MS, Burnett RT,
Yale J-F,
A longitudinal study
to identify factors that trigger ventricular tachyarrhythmias among persons
with implanted cardioverter defibrillators
Granting agency: CIHR
PI: M S Goldberg and Paul Khairy
Collaborators: J. BROPHY, R. BURNETT, V. ESSEBAG, T. HADJIS, N. MAYO, S. MILLER, M.
TALAJIC
Sudden cardiac death
from heart rhythm disorders (arrhythmias) is one of the leading causes of death in
Unfortunately, there is scant
information regarding the association between triggering factors and the
frequency of tachyarrhythmias in ICD patients, with a handful of studies
suggesting that increases in air pollution and changing weather conditions
(e.g., high temperatures) may affect event rates. It is important to identify transient
factors, especially those that are modifiable, so that potentially fatal
arrhythmias and mortality can be reduced, especially amongst those who are
being treated aggressively. Widespread
use of ICDs provide an opportunity for investigating these triggering factors,
and is the only way that arrhythmias can be investigated. Thus, the primary purpose of this study is to
identify personal, pharmaceutical, and environmental factors that may increase
the occurrence of from ICDs to treat ventricular tachycardia, including pacing,
as well triggering factors for “inappropriate treatment”.
This is a longitudinal,
prospective, inception cohort study of about 500 persons, age 50-75 years,
living in
We will record data at
baseline and a questionnaire will be self-administered periodically and at the
time of a perceived therapeutic intervention (shock) to describe potential
personal triggering factors (e.g., physical activity, psychological stress,
physical activity). Subjects will be trained as to how to fill in the
questionnaires and follow the protocol. We will institute a series of active
procedures to follow subjects closely through time, thereby maximizing response
rates. We will also obtain data on medical procedures, drugs, hospitalization,
mortality, etc. from provincial medicare files and environmental data (air
pollution, weather) from fixed-site monitors.
Our principal health endpoint
will be ventricular tachyarrhythmias, which is a recurrent, non-absorbing
binary outcome. Analyses will be based on case-crossover as well as random
effects binary logistic models. The
case-crossover design is analogous to a matched case-control study, in which
exposure during a case-period is compared with exposure during one or more
control periods sampled from that same individual at different time points.
Thus, within-subject comparisons are made across time and then “averaged”
across subjects. We will thus be able to
investigate a variety of personal and environmental triggers. This study will
therefore provide valuable data on aetiology, it will provide insights into
mechanisms through a longitudinal follow-up of a cohort of high risk subjects,
and it may provide data to suggest strategies to reduce these potentially fatal
events and, consequently, to reduce sudden cardiac death.
longitudinal study of Acute effects OF ambient air pollution in
susceptible populations
Granting agency: CIHR
PI: M S Goldberg
Collaborators: Richard Burnett, Kenneth Flegel, Nadia Giannetti, Michal Abrahamowicz, Robert Platt
Abstract: Despite the general
reduction in pollution levels, short-term exposures to ambient air pollutants generated
from the combustion of fossil fuels have been found to be associated with
increased hospitalizations and deaths. The evidence derives mostly from
parallel time series studies, which are used to answer the question “are there increases in numbers of
hospitalizations or deaths on the day or
the next few days following an increase in the level of air pollution?”. Studies have been carried out in countries
with varied levels of industrialization and air pollution, and the results have
been extremely consistent regardless of the extent of pollution or the mix of
pollutants. It has been hypothesized
that only persons in poor health should be affected by the relatively low
levels of air pollution present today. The hypotheses focus on persons with
cardiopulmonary disease and those in poor and failing health who because of
their illness are susceptible to the adverse effects of air pollution. The
identification of mechanisms is essential and, although the toxicology is
progressing, epidemiological studies are required to uncover which subgroups of
the population are susceptible to the effects of air pollution. This protocol addresses this issue through a
longitudinal study of selected subgroups to identify whether the incidence of
certain health outcomes are correlated with short-term changes in air
pollution.
The principal objective of this
longitudinal study is to determine among multiple cohorts of persons with
specific health conditions whether short-term changes in air pollution, on the
order of days, are associated with the incidence of critical indicators of
health, including death, hospitalizations, emergency room visits, and selected
“intermediate health events”. Specific objectives are: 1) for selected
conditions (e.g., congestive heart failure), to define intermediate health
events (e.g., changes in medication signaling an adverse health event) and
develop algorithms to identify these from administrative health data and 2) to
conduct a series of statistical analyses using a Poisson point process model
developed by Dewanji and Moolgakavkar that will provide estimates of
associations between short-term changes in air pollution and the
above-mentioned indicators of health.
The study is designed as a longitudinal
cohort of men and women who are residents of
Publications:
Goldberg MS, Burnett RT.
A new longitudinal design for identifying subgroups of the population
who are susceptible to the short-term effects of ambient air pollution. J Toxicol. Environ Health A 2005;68(13-14),
1111-1125.
The short-term effects of ambient air pollution on clinical signs
and symptoms for congestive heart failure: A pilot study
Granting agency: Canadian
Institutes of Health Research
PI: Mark Goldberg
Collaborators: BURNETT, Richard; FLEGEL, Kenneth; GIANNETTI, Nadia; MAYO, Nancy E; TAMBLYN, Robyn; VINCENT, Renaud
Abstract: Although ambient levels of pollution have
declined in the past 40 years, recent studies have shown that short-term
exposures to ambient air pollutants generated from the combustion of fossil
fuels cause exacerbations of cardio-respiratory disease that result in
hospitalization and death. An important unanswered question is "which
subgroups of the population may be susceptible to the effects of ambient air
pollution?". One of the most susceptible subgroups may be individuals with
congestive heart failure (CHF): much higher rates of hospitalization and death
are found in this group when air pollution increases. There is no information
regarding the time course of changes in health status of these individuals nor
how these changes are linked to variations in ambient air pollution. We thus
seek to determine whether changes in key indicators of health status in
subjects with CHF are associated with variations in levels of air pollution.
Because of the complexities involved in such a study, we need to first test the
feasibility of various aspects of conducting such a study as well as to pilot
various aspects of the study.
Publications:
Goldberg
MS, Giannetti
N, Burnett RT, Mayo NE,
Goldberg
MS, Giannetti,
N, Burnett RT, Mayo NE,
A panel study of the effects of changing lifestyle and environmental
conditions on signs and symptoms in heart failure
Granting agency: Health
PI: Mark Goldberg
Collaborators: Amanda Wheeler, Nadia Giannetti, Eileen O'Meara, Nancy E. Mayo, James Brophy, Richard T. Burnett
Heart failure
(HF) is a complex clinical syndrome resulting from any cardiac condition that
impairs the ability of the heart to pump blood from the ventricles. It causes
serious fatigue, dyspnea on exertion and then at rest and, thus, reduces the ability
to conduct activities of daily living. It
is a chronic and progressive disease resulting in frequent visits to outpatient
clinics and emergency departments, frequent admissions to hospital, and is
often fatal. Incidence rates are very high and increase by age: for example, in
the
The purpose of
the present study is to determine among patients with HF whether daily changes
in selected signs, symptoms, and physiologic indicators are associated with
daily changes in selected personal characteristics/lifestyle and with daily
variations in environmental conditions. This is a study of acute effects. A motivation
for the study is the lack of identified modifiable personal risk factors for
decompensated HF and little understanding of the causal pathways from
sub-clinical to adverse states of health. A second motivation derives from
findings of environmental studies of acute effects that showed that daily hospitalizations
and daily mortality among persons with HF increase when ambient temperature and
when levels of ambient air pollution increases.
Identification of modifiable factors can be used in clinical practice to
improve outcomes and these data will also assist in more fully understanding
mechanisms by which patients experience decompensated HF. Through the support
of CIHR (MOP-49397), Goldberg and colleagues conducted a feasibility study to
determine whether potential subjects i) would agree to participate in a study,
ii) whether participants and non-participants would be comparable, and iii)
whether participating subjects would be able to record data on a daily
basis. We have concluded that the main
study is feasible: the participation rate was 86%; subjects were able to
complete the study protocol (e.g., only 3.2% of data were missing); and we have
data to improve the design (e.g., the daily diary) and estimate sample size.
We propose a daily
diary panel study and 200 subjects will participate over a two month,
consecutive period. They will comprise a
consecutive series of outpatients who receive health care at HF clinics in two
major teaching hospitals in
Air Pollution: Long-Term Effects
Reanalysis of the Harvard Six-Cities Study and the American Cancer
Society Study of Air Pollution and Mortality
Granting agency: Health Effects Institute,
PI: Daniel Krewski (
Collaborators: Richard Burnett, Mark Goldberg, Jack Siemiatycki.
Abstract: The
overall objective of the project is to conduct a rigorous and independent
assessment of the findings of the Six-Cities and ACS studies of air pollution
and mortality. The project has two main
tasks: 1) Attempt to validate and replicate the published results by: conducting a quality assurance audit on a
sample of the original data; attempting to reproduce the original numerical
results. 2) Conduct sensitivity analyses to test the robustness of the original
findings and interpretations to alternative analytic approaches.
Publications:
Krewski D, Burnett R, Goldberg MS, Siemiatycki J, et al.. Re-analysis
of the Harvard Six-cities and American Cancer Society Cohort Studies of
Particulate Air Pollution and Mortality, Phase II: Sensitivity Analysis.
Health Effects Institute,
Richard Burnett,
Renjun Ma, Michael Jerrett, Mark S.
Goldberg, Sabit Cakmak, C. Arden Pope III, Daniel Krewski. The Spatial
Association Between Community Air Pollution and Mortality: A New Method of
Analyzing Correlated Geographical Cohort Data. Env Health Perspect 109(Suppl 3):375-80, 2001.
Richard Burnett,
Renjun Ma, Michael Jerrett, Mark S.
Goldberg, Sabit Cakmak, C. Arden Pope III, Daniel Krewski. The
Space-time Association Between Community Air Pollution and Mortality: A New
Method of Analyzing Correlated Geographical Cohort Data. Statistical Society of
Paul
J. Villeneuve, Dan Krewski, Richard T. Burnett, Mark S. Goldberg, Yue Chen, Jack Siemiatycki. Fine particulate air
pollution and all-cause mortality within the Harvard Six-Cities study:
variations in risk by period of exposure. Annals
of Epidemiol, 2002;12(8):568-576.
Krewski,
D; Burnett, R; Goldberg, M; Hoover,
K; Siemiatycki, J; Abrahamowicz, M; White, W. Reanalysis of
Harvard Six Cities Study, Part I.
Validation and Replication. Inhalation Toxicology,
2005;17(7):343-352
Krewski,
D; Burnett, R; Goldberg, M; Hoover,
K; Siemiatycki, J; Abrahamowicz, M; Villeneuve, P; White, W. Reanalysis of
Harvard Six Cities Study, Part II. Sensitivity Analysis. Inhalation
Toxicology, 2005;17(7):335-42
Sabit Cakmak, Richard T. Burnett, Michael Jerrett, Mark S. Goldberg,
C. Arden Pope III, Renjun Ma, Timur Gultekin, Michael
J. Thun, Daniel Krewski. Spatial Regression Models for Large Cohort Studies
Linking Community Air Pollution and Health.
Journal of Toxicology and Environmental Health, 2003;66 (Numbers
16-19), 1811-1824.
Jerrett M, Burnett RT, Goldberg
MS, Sears M, Krewski D, Catalan R et al. Spatial analysis for environmental
health research: concepts, methods, and examples. J Toxicol Environ Health A 2003; 66(16-19):1783-1810.
Jerrett, M., R. Burnett, A. Willis, D. Krewski, M.S. Goldberg, P.
DeLuca, N. Finkelstein. Spatial analysis of the air pollution-mortality
relationship in the context of ecologic confounders. Journal of Toxicology
and Environmental Health, 66 (Numbers 16-19), 1735-1778, 2003.
Daniel Krewski, Richard T. Burnett, Mark
S. Goldberg, Michal Abrahamowicz, Jack Siemiatycki, Michael Jerrett, B.
Kristen Hoover. Rejoinder: Reanalysis of
the Harvard Six Cities Study and American Cancer Society Study of Particulate
Air Pollution and Mortality. The Journal
of Toxicology and Environmental Health, 66 (Numbers 16-19), 1715-1722, 2003.
Jack Siemiatycki, Daniel Krewski, Mark
Goldberg, Yuanli Shi, Louise Nadon, Ramzan Lakhani. Control of Occupational Confounding in the
Harvard Six Cities Study and American Cancer Society Study. The Journal of Toxicology and Environmental
Health, 66 (Numbers 16-19), 1591-1604, 2003.
Alette Willis, Daniel Krewski, Michael Jerrett, Mark Goldberg, RT Burnett. Selection of Ecologic Covariates in the
American Cancer Society Study. The Journal of Toxicology and Environmental
Health, 66 (Numbers 16-19), 1563-1590, 2003.
B. Kristin Hoover, Donna E. Foliart, Warren H. White, Aaron J. Cohen,
Linda J. Calisti, Daniel Krewski, Mark
S. Goldberg. Retrospective Data
Quality Audits of the
Krewski D, Burnett RT, Goldberg
MS, Hoover K, Siemiatycki J, Jerrett M, Abrahamowicz M, Warren H. Overview of the reanalysis of the Harvard six
cities study and American Cancer Society study of particulate air pollution and
mortality. The Journal of Toxicology and
Environmental Health, 66 (Numbers 16-19), 1507-52, 2003.
Cancer
incidence and mortality among adults in relation to long-term exposure to
outdoor air pollution: A general population cohort study of
Granting agency: CIHR
PI: Paul Villeneuve
Collaborators: JR. BURNETT, M S Goldberg,
R Ma
The purpose of this study is to determine whether
long-term exposure to air pollution is associated with the occurrence of cancer
and other causes of death in a cohort of adults who were resident in one of 10
urban centres in
The cohort will be constructed by identifying
individuals, 40 years of age and older, from the T1-Family File (T1FF)
database. This database contains information from annual income tax T1 forms
and includes all persons who filed Federal tax returns as well as any family
members identified on the tax returns from 1982 onwards. To be included in the
cohort, individuals had to be resident in one of 10 urban centres for at least
one tax filing between 1982 and 1986. Internal linkage within the T1FF will
allow for the residential mobility of these individuals to be tracked each year
from 1982 until 2001. Mortality and cancer incidence within the cohort will be
ascertained by linking personal identifying information in the T1FF database to
the Canadian Cancer Registry and
Vital Statistics Death databases.
Air pollution exposures will be assigned to each
individual using data from fixed-site monitoring stations from the National Air
Pollution Surveillance network. Annual air pollution indices will be created
for O3, SO2, and total suspended particulates. An ?extended?
Cox regression model will examine
associations between air pollution and health outcomes, including: all cancers,
lung cancer, and cardiovascular and respiratory mortality. The extent by which
socioeconomic status modifies the air pollution risk estimates will be
evaluated using reported income from the T1FF.
While individual-level income data are available for
our cohort on an annual basis, information for other covariate information is
missing (e.g., smoking). Not adjusting
for key risk factors may lead to biased estimates if there are large
discrepancies in prevalence between the different the cities included in the
present study. Using data from the
Ontario Health Survey, we will use an indirect method to account for smoking,
alcohol consumption, and physical activity on the risk estimates for air
pollution.
In summary, the
large number of persons exposed to higher levels of air pollution in Ontario,
the capability of assembling a general-population based cohort with individual
level indicators of socioeconomic status, the ability to trace the residential
mobility of this population, and the availability of retrospective air
monitoring data, together, provide a unique opportunity to investigate the
relationship between long-term exposure to air pollution and chronic health
effects.
Publications:
Hong Chen*, Mark S. Goldberg, Paul J. Villeneuve. A
Systematic Review of Relation between Long-term Exposure to Ambient Air
Pollution and Chronic Diseases. Submitted to Reviews of Environmental Health, Rev
Environ Health, 2008.
Traffic-related air pollution and socioeconomic gradients in the incidence of cancer
Granting agency: CIHR
PI: M S Goldberg
Collaborators: Michael Jerrett, Nancy Ross, Nicolas Gilbert, Jeffrey Brook, Renjun
Ma, Richard Burnett, Claire
Infante-Rivard, Jack Siemiatycki
Abstract: It has been found that
short-term exposures to ambient air pollutants generated from the combustion of
fossil fuels are associated with increased hospitalizations and deaths. It has
been hypothesized that only persons in poor health should be affected by the
relatively low levels of air pollution present today. The hypotheses focus on
persons with cardiopulmonary disease and those in poor and failing health who
because of their illness are susceptible to the adverse effects of air
pollution. In addition, it has also been
observed from cohort and case-control studies that there may be associations between
long-term exposures to air pollution and lung cancer and childhood
leukemia. Results from three cohort
studies have indicated that the chronic effects may be mediated by
socio-economic status; this implies that
either local levels of air pollution in socio-economically disadvantaged areas
are higher than implied by average city-wide levels or that individuals living
in these areas are at higher risk, or both.
We are proposing to determine in Montreal
whether 1) chronic health effects are associated with long-term effects of
local levels of ambient air pollution, respectively, and are associated with
indicators of socio-economic status and 2) whether socio-economic status
modifies the effects of air pollution (and vice versa). (
Publications:
Dan Crouse*, Nancy Ross, Mark S. Goldberg. Neighbourhood-scale Socioeconomic and Environmental Risks in
Dan Crouse*, Mark S. Goldberg
Nancy Ross, Michael Jerrett Modelling Temporal and Spatial Variability of Ambient Air Pollution in
Breast Cancer Research
Gene-environment interactions in postmenopausal breast cancer: A
case-control study
Granting agency: CIHR
PI: M S Goldberg
Collaborators: Jacques Simard,
Francine Durocher, France Labrèche, Marie-Élise Parent, Bryan Langholz
Abstract: Female breast cancer is
a major public health concern in the industrialised world. It is the most commonly diagnosed malignancy
among Canadian women, and it accounts for about 30 percent of all new cases of
cancer. About one in nine Canadian women
is expected to develop breast cancer in her lifetime and one in 25 women is
expected to die from the disease. It is
the second most common cause of death from cancer, accounting in 1999 for an
estimated 18% of all cancer deaths among Canadian women.
We and others have postulated that
exposures to certain chemical and physical agents may increase the risk of
developing breast cancer, including pesticides, polycyclic aromatic
hydrocarbons (PAH), organic solvents, and magnetic fields (EMF) and
light-at-night. Common genetic polymorphisms of low penetrance such as those
that code for the cytochrome P450 Phase I oxidizing enzymes (the family of CYP
genes) and Phase II detoxifying or conjugating enzymes (e.g., glutathione
s-transferase (GST) and n-acetyl transferase (NAT)) are only recently drawing
researchers’ interest. Cytochrome P450 enzymes are important factors in
steroidogenesis and in detoxifying environmental chemicals such as PAHs and
benzo(a)pyrene. Research in
gene-environment interactions in breast cancer is in its infancy, with only a
handful of high quality studies that have been completed.
The objective of the present proposal is
to determine whether common polymorphisms for selected genes (e.g., CYP1A1,
GSTs, NATs, COMT, HRAS1) combined with lifestyle/demographic characteristics
(e.g., alcohol, physical activity, reproductive
factors, body size,
hormonal replacement therapy, exposure to light-at-night and shift work) are
associated with the incidence of postmenopausal breast cancer. A population-based case-control design will
be used to enrol 1,800 incident, histologically-confirmed cases of
postmenopausal breast cancer from all major hospitals in
Breast cancer in women and exposure to occupational and
environmental substances
Granting agency: Canadian Breast Cancer Research Initiative
PI: Mark Goldberg
Collaborators:
Abstract: Although
progress has been made in limiting the progression of female breast cancer
through surgical and chemical adjuvant treatments, we are unfortunately left
with the grim picture that breast cancer incidence continues to increase
unabated. In
The case-control study
that we describe herein is the first major investigation of invasive breast
cancer and its relationship with occupation.
Our underlying hypothesis is that there are chemical and physical agents
present in the workplace that may induce breast cancer. In particular, we have developed an
hypothesis that exposure to organic solvents is associated with the incidence
of breast cancer. The study uses
cutting-edge methodology to assess past occupational exposures. Coupled with this and other design features
of the study, we will test the hypothesis that organic solvents are associated
with postmenopausal female breast cancer.
As well, we will assess risk for a wide range of occupational risk
factors that have not been hitherto investigated. From a public health point of view,
identification of new agents whose exposures are amenable to modification will
allow new public health initiatives to reduce risk.
The present study is
meant as a first step to investigating occupation and, to a lesser extent, the
general environment. We hypothesize that
there are chemical and physical agents present in the workplace that may induce
breast cancer. In particular, we have
developed an hypothesis that exposure to organic solvents is associated with
the incidence of breast cancer. The
present investigation is the first major study of invasive breast cancer and
its relationship with occupation. The
objective of the study is to determine whether exposure to organic solvents and
exposure to selected chemical and physical agents are associated with the
incidence of post-menopausal malignant breast cancer in women. Subjects will be incident,
histologically-confirmed cases of breast cancer aged 51-70 years diagnosed in
Publications:
Goldberg
MS, Labrèche F. Occupational risk factors for
female breast cancer: A review. Occupational
and Environmental Medicine, 1996; 53:145-56.
Labrèche F, Goldberg MS. Exposure to organic solvents cause breast cancer in
women: A hypothesis. Am J Indust Med, 1997; 32:1-14.
Lenz
SK, Goldberg MS, Labrèche F, Parent
M-É, Valois M-F. The association between alcohol consumption and
postmenopausal breast cancer: Results of A case-control study in
Labrèche F, Goldberg MS, Valois M-F, Nadon
L, Richardson L, Lakhani R, Latreille B. Occupational Exposures to Extremely
Low Frequency Magnetic Fields and Postmenopausal Breast Cancer. Am J Indust Med, 2003, 44:643-52.
Waiting time for breast cancer surgery: An analysis of
Granting agency: Canadian Breast Cancer Research Initiative
PI: Nancy E Mayo (
Collaborators: Mark Goldberg, Richard Margolese, John Sampalis, Jeannie Haggerty, Jim Hanley
Abstract: The purpose of this study is to determine
the amount of time that women in
Publications:
Mayo N, Scott S,
Shen
N,
Fortin Bernard, Goldberg MS, Mayo NE, Valois M-F,
Scott SC, Hanley J. Waiting Time for Radiation Therapy in Breast Cancer
Patients in Quebec from 1992 to 1998. A study of
surgically treated breast cancer patients in
The Occurrence of Arm Dysfunction and Lymphedema After Treatment for
Stage I or II Breast Cancer
Granting agency: CIHR, CBCRI
PI: M S Goldberg
Collaborators: Nancy Mayo, Sarkis Meterissian
Abstract: Breast carcinoma is the
most frequently occurring cancer in women.
Survival rates after breast cancer have been increasing and this is due
partly to improved diagnostic and therapeutic techniques. One frequent source of morbidity post-surgery
is lymphedema and arm dysfunction, which may entail weakness, stiffness, pain,
edema, loss or change in sensation, decreased fine motor coordination, and
restricted range of motion. These arm
problems may be associated with axillary dissection, a procedure performed on
the majority of women undergoing breast cancer surgery. Research on arm morbidity has focused on the
problem of lymphedema, which is the result of a functional overload of the
lymphatic system in which lymphatic volume exceeds transport capabilities. Chronic lymphedema (present for at least 3
months) has noticeable changes in skin colour and texture and can cause chronic
arm dysfunction. Treatment includes elevation, massage and exercise, and
application of external pressure with compression garments or compression
pumps. These methods give a wide range
of results, depending on the subject and timing of treatment, but may only lead
to partial improvement. Lymphedema
persisting over a long period results in hypertrophy of the subcutaneous fat
tissue and development of fibrosis, both of which make compression therapy less
effective. Thus, it is thought that
early identification of patients with lymphedema is important since compression
therapy seems to be more effective the shorter the time the edema has
persisted.
The literature on lymphedema is rather
sketchy and its interpretation is plagued by difficulties in its
definition. There are very little data
on arm dysfunction. The objective of the
present study is to increase our limited understanding regarding the
relationships between lymphedema, arm dysfunction, and quality of life among
women treated for stage I or II breast cancer and to identify important risk
factors for lymphedema and arm dysfunction.
Specifically, we will 1) estimate the prevalence, extent, and impact on
quality of life of lymphedema and arm dysfunction after treatment for stage I
or II breast cancer: 2) define the
association between the presence and degree of lymphedema and arm dysfunction;
and 3) identify risk factors for the development of lymphedema and arm
dysfunction post-treatment.
The study is designed as a follow-up of
patients treated at the McGill University Hospital Centre (MUHC) between 1992
and 2002. We will make use of the MUHC
Cancer Registry to identify patients, obtain relevant clinical data, and
address information. We will trace
subjects and they will fill out a “screening” questionnaire about signs and
symptoms of lymphedema and a set of questionnaires on arm dysfunction and
quality of life. Women who are
positive on the screening questionnaire will be invited for a clinical
evaluation as well as a random sample of persons who are negative (to estimate
sensitivity and specificity). These data
will allow us to answer the three objectives of the study. In identifying those patients at greatest
risk of developing these complications, we may be able to determine which ones
may benefit from sentinel lymph node mapping.
This study may eventually make the long-term follow-up of breast cancer
survivors routine and may lead eventually to randomized studies to determine
optimal treatment regimens.
Publications:
Diana
J. Dawes, Sarkis Meterissian, Mark
Goldberg, Nancy E. Mayo. Impact of
Lymphoedema on Arm Function and Health-Related Quality of Life in Women
following Breast Cancer Surgery. J
Rehabil Med, 2008; 40: 651–658.
Prostate Cancer Research
Occupational and lifestyle factors in the etiology of prostate
cancer, and establishing a platform for studying susceptibility biomarkers
Granting agency: National Cancer
Institute of
PI: M-E Parent
Collaborators: J Siemiatycki, K Aronson, Mark Goldberg
Abstract: The present study will explore, using
expert-based exposure assessment, the role of some 100 occupational substances
which appear the most promising based on the evidence from studies of
occupational groups or based on their suspected biological role. Moreover, we
will assess the role of selected lifestyle factors which have received
relatively little attention to date, i.e., physical activity (occupational,
household, recreational), sexual habits, lifetime body size and abdominal
obesity, smoking, and alcohol. Finally, we will collect biological specimen in
order to be able to assess the role of relevant genetic polymorphisms
(carcinogen metabolizing and hormone-related genes) which may influence the degree
of susceptibility of developing prostate cancer either alone, or in combination
with occupational or lifestyle risk factors. We propose to carry out a
population-based case-control study of prostate cancer. Eligible subjects will
be males, aged under 76, resident in the
Epidemiological Methods and Biostatistics
Regression modelling of continuous covariates in epidemiology: A simulation study of nonparametric smoothers
Granting agency: Canadian
Institutes of Health Research
PI: Michal Abrahamowicz
Collaborators: Mark Goldberg, Karen Leffondre
Abstract: Modern statistical analysis of data arising
from investigations in epidemiology, clinical medicine, and the social sciences
make extensive use of multiple regression techniques to estimate associations
between outcome and explanatory variables. For continuously measured
covariates, parametric representations of the response function are generally
used. Current methods for estimating the shape of the response function are
inadequate, possibly resulting in incorrect specification of the model and
possible residual confounding effects. Nonparametric regression methods relax
the strict assumptions imposed by the parametric representations thereby
allowing the data to dictate the appropriate functional form. Although these
flexible methods are well-developed and are available in some software
packages, there are a number of outstanding problems that need to be tackled.
Thus, the objectives of this simulation study are to evaluate different
nonparametric smoothers to determine which methods and what amount of smoothing
more accurately represent the true response functions, and to identify the most
accurate model selection criteria. The simulations studies will cover a wide
class of GLMs, the Cox model, different response functions for the main
exposure variable, and different response functions for the covariates. in
addition, we will develop some new computational routines to facilitate
inference about nonparametric estimates.
Publications:
Jiguo
Cao, Marie-France Valois, Mark S.
Goldberg. An
S-Plus Function to Calculate Relative Risks for Regression Models Using Natural
Splines. Computer Methods and Programs in
Biomedicine. 2006;84(1):58-62.
A Benedetti, M Abrahamowicz, Goldberg, MS. Accounting for
data-dependent degrees of freedom selection when testing the effect of a
continuous covariate in generalized additive models, In press, Communications
in Statistics - Simulation and Computation.