GRACE CHEN
18TH OCTOBER, 2014
OCCUPATIONAL AND ENVIRONMENTAL
RISK FACTORS FOR MOTOR NEURONE
DISEASE IN NZ
Case - Control Study
Very little is known about the causes of Motor
Neurone Disease. Our study is to investigate the
relationship between MND in New Zealand and a
range of known or suspected occupational and
environmental exposures.
OCCUPATIONAL AND ENVIRONMENTAL RISK
FACTORS FOR MOTOR NEURON DISEASE
This will be the first New Zealand study to
investigate these potential risk factors, and it
will allow comparisons to be made with MND
in other developed countries.
OCCUPATIONAL AND ENVIRONMENTAL RISK
FACTORS FOR MOTOR NEURON DISEASE
WHAT IS MOTOR NEURON DISEASE
The motor neuron diseases (MNDs) are a group
of progressive neurological disorders that
destroy motor neurons, the cells that control
essential voluntary muscle activity such as
upper and lower limb activities, speaking,
breathing, and swallowing.
OCCUPATIONAL AND ENVIRONMENTAL RISK
FACTORS FOR MOTOR NEURON DISEASE
BACKGROUND AND EPIDEMIOLOGY OF MND
• MND is uncommon but not rare and there is no
cure or standard treatment for MND.
• Death usually results from respiratory failure and
other lung complications, on average about 3
years after the first symptoms of weakness
appear.
• Most MND cases are sporadic, familial
( inherited ) forms of MND account for less than
10% of cases.
OCCUPATIONAL AND ENVIRONMENTAL RISK
FACTORS FOR MOTOR NEURON DISEASE
BACKGROUND AND EPIDEMIOLOGY OF MND
• Highest incidence at age 70 years
• MND is more common in males than females
with a ratio of 3:2.
• There has been some evidence of increasing
incidence and mortality rates in developed
countries in the last two decades.
OCCUPATIONAL AND ENVIRONMENTAL RISK
FACTORS FOR MOTOR NEURON DISEASE
BACKGROUND AND EPIDEMIOLOGY OF MND
In New Zealand
• 300 cases in NZ at any one time (7/100,000 pa)
• 100 new cases each year (2/100,000 pa)
• Some evidence of increasing incidence in New Zealand
• Ageing population in NZ
(New Zealand has an ageing population, with the proportion aged 65
years or older increasing from 11.8% to 13.1% during 2000- 2010)
The ageing population and increasing incidence mean that the number of
MND cases in New Zealand is expected to rise.
OCCUPATIONAL AND ENVIRONMENTAL RISK
FACTORS FOR MOTOR NEURON DISEASE
POTENTIAL OCCUPATIONAL AND
ENVIRONMENTAL RISK FACTORS FOR MND
Occupational risk factors:
• Agricultural chemicals
• Electrical occupations/Electromagnetic fields (EMF)/ Electric shock
• Neurotoxic agents : solvents，lead, mercury or other heavy metals
• Welding
• Fumigants : methyl bromide
• A range of chemicals in occupations: textile workers, veterinarians,
hairdressers
• Military service
OCCUPATIONAL AND ENVIRONMENTAL RISK
FACTORS FOR MOTOR NEURON DISEASE
POTENTIAL OCCUPATIONAL AND
ENVIRONMENTAL RISK FACTORS FOR MND
Environmental and other risk factors:
• Rural vs. urban residence
• Smoking
• Head trauma (history of head injury including
sporting injuries)
OCCUPATIONAL AND ENVIRONMENTAL RISK
FACTORS FOR MOTOR NEURON DISEASE
INTERNATIONAL STUDY - 1
- Pesticide exposure and MND
A meta-analysis of epidemiological studies. Malek et al, 2012.
• A meta-analysis of 6 epidemiological studies
published to 2011.
• Total 592 cases from 6 studies
Result:
exposure to pesticides had a risk of develop MND
Summary OR=1.88, (95% CI 1.36 – 2.61)
OCCUPATIONAL AND ENVIRONMENTAL RISK
FACTORS FOR MOTOR NEURON DISEASE
INTERNATIONAL STUDY - 2
- Chemical exposures and ALS
American Cohort study: Weisskopf et al, 2009
•
•
•
•
over 1 million participants from American Cancer Society's Cancer Prevention Study II.
Follow-up from 1989 through 2004
Individuals exposed to pesticides/herbicides compared to the unexposed
identified 617 male and 539 female deaths from ALS
Result
Exposures
RR
Pesticides/herbicides
(excluding those with missing
duration of pesticides exposure )
1.44 ( 95% CI: 0.89-2.31)
Formaldehyde
1.34 ( 95% CI: 0.93-1.92)
*There was a strongly dose-response relation with increasing years of exposure .
OCCUPATIONAL AND ENVIRONMENTAL RISK
FACTORS FOR MOTOR NEURON DISEASE
INTERNATIONAL STUDY - 3
Workplace exposure and ALS
American case control study, Fang, et al ,2009
• 109 cases and 253 control (3 years)
• Compare detailed occupation and workplace exposure
Result:
Occupation
Precision metal workers
OR (95% CI)
3.5 (1.2-10.5)
Construction workers
2.9 (1.2-7.2)
OCCUPATIONAL AND ENVIRONMENTAL RISK
FACTORS FOR MOTOR NEURON DISEASE
INTERNATIONAL STUDY - 3
Workplace exposure and ALS continue…
Self-reported exposures to :
• paint strippers;
• cooling, lubricating oils;
• antifreeze or coolants;
• mineral or white spirits;
• dry cleaning agents
each exposure appeared to be associated with a
60–90% higher risk.
OCCUPATIONAL AND ENVIRONMENTAL RISK
FACTORS FOR MOTOR NEURON DISEASE
INTERNATIONAL STUDY – 4
Head injury and ALS
Oxford Record Linkage Study Turner et al, 2010.
• hospital records 1963 - 1999.
• Follow up all in-patients for head injury.
ALS rate after head injury RR=1.5 (95% CI 1.1 – 2.1).
Swedish Case and control study, Peters et al, 2013.
4004 Swedish cases and 20,020 controls.
Conclusions: Similar finding of elevated ALS risk with
severe head injury.
OCCUPATIONAL AND ENVIRONMENTAL RISK
FACTORS FOR MOTOR NEURON DISEASE
INTERNATIONAL STUDY – 5
Smoking, alcohol consumption, and the risk of MND
Dutch Case-Control study. De Jong et al, 2012
494 cases, 1,599 controls.
Results:
Current smokers OR = 1.38, 95% CI 1.02 – 1.88.
Current smoking also associated with shorter survival
HR = 1.51, 95% CI 1.07 – 2.15.
(HR= hazard risk)
Current alcohol consumption is a protected factor.
OR = 0.52, 95% CI 0.40 – 0.75.
Conclusions:
- Current smoking increases risk.
- Alcohol consumption reduces risk
OCCUPATIONAL AND ENVIRONMENTAL RISK
FACTORS FOR MOTOR NEURON DISEASE
“If MND had just one cause, researchers would have found it a
long time ago”.
Dr Brian Dickie
Director of Research Development
UK MND Association
OCCUPATIONAL AND ENVIRONMENTAL RISK
FACTORS FOR MOTOR NEURON DISEASE
NEW ZEALAND POPULATION BASED CASECONTROL STUDY
The study will recruit 400 cases and 800 controls.
Cases will be diagnosed for MND by neurologists and will be recruited
directly from the Motor Neuron Disease Association New Zealand
(MNDANZ) and/or neurologists throughout the country.
Controls will be selected from the New Zealand Electoral Roll, with two
controls for each case, matched for age and gender. The controls will
thus be representative of the general population that generated the
cases.
OCCUPATIONAL AND ENVIRONMENTAL RISK
FACTORS FOR MOTOR NEURON DISEASE
NEW ZEALAND POPULATION BASED CASECONTROL STUDY
The methods used to collect the data will be the
same for both cases and controls
• face-to-face interviews
• telephone interviews
• postal questionnaires
(depending on the preference of the participant).
OCCUPATIONAL AND ENVIRONMENTAL RISK
FACTORS FOR MOTOR NEURON DISEASE
NEW ZEALAND POPULATION BASED CASECONTROL STUDY
Standard questionnaire (16 parts) to obtain information
on:
– demographic details
– residential history
– lifestyle factors
– complete occupational history
– Agriculture questions
OCCUPATIONAL AND ENVIRONMENTAL RISK
FACTORS FOR MOTOR NEURON DISEASE
NEW ZEALAND POPULATION BASED CASECONTROL STUDY
Occupational exposure determined through use of Job
Exposure Matrices
Environmental exposure determined through EPA data
on location of use of specific chemicals - linked to
information on residence.
OCCUPATIONAL AND ENVIRONMENTAL RISK
FACTORS FOR MOTOR NEURON DISEASE
NEW ZEALAND POPULATION BASED CASECONTROL STUDY
Result to date
For cases:
• 217 invitation letters have been sent.
• 199 replied (92%).
• Of those 199, 176 agreed to take part in the study
• 164 have been interviewed, 12 cases are in progress
For Controls:
• 1600 invitation letters have been sent out,
• 814 replied (51%).
• Of those 814, 392 participated in the study.
• 245 have been interviewed, 147 are in progress.
OCCUPATIONAL AND ENVIRONMENTAL RISK
FACTORS FOR MOTOR NEURON DISEASE
DETAILS OF CASES
Total cases :176
112 Males
64 Females
Male/Female ratio  3:2
Age group:
• 107 cases (61%) are in the age 60 -74
 30 cases (17%) are in the age 60-64
 44 cases (25%) are in the age 65-69
 33 cases ( 19%) are in the age 70-74
• 11 cases are over 80
• 3 cases are under 40
OCCUPATIONAL AND ENVIRONMENTAL RISK
FACTORS FOR MOTOR NEURON DISEASE
25%
20%
15%
10%
5%
0%
Age
<40
41-49 50-54 55-59 60-64 65-69 70-74 75-79
CASES AGE GROUPS
Age
>80
CASES ACCORDING TO DHB
CASES ACCORDING TO DHB
Completed
interviewed
Interviews are in
progress
Northland
Auckland
9
12
1
3
Waikato
Bay of Plenty
Taranaki
Wanganui
Hutt Valley
Wairarapa
West Coast
South Canterbury
Southland
DHB
DHB
Completed
interviewed
Waitemata
Counties Manukau
8
4
21
Lakes
3
10
2
1
4
2
3
6
4
74
Tairawhiti
Hawke’s Bay
MidCentral
Capital and Coast
Nelson Marlborough
Canterbury
Otago
Southern
1
3
6
19
11
20
5
10
90
1
5
Total
OCCUPATIONAL AND ENVIRONMENTAL RISK
FACTORS FOR MOTOR NEURON DISEASE
164
Interviews are in
progress
2
1
4
7
12
OCCUPATIONAL AND ENVIRONMENTAL RISK
FACTORS FOR MOTOR NEURON DISEASE
OCCUPATIONAL AND ENVIRONMENTAL RISK
FACTORS FOR MOTOR NEURON DISEASE
Thank you for all your support
OCCUPATIONAL AND ENVIRONMENTAL RISK
FACTORS FOR MOTOR NEURON DISEASE