Memorandum submitted by Professor David
Forman
PROGRESS ON PESTICIDES
BACKGROUND
1. I am currently Professor of Cancer Epidemiology
at the University of Leeds. I have been a member of the COC, as
an independent epidemiologist, for almost 10 years.
2. The COC is comprised of 12 independent
members (including two lay members) and an independent chair (Professor
P G Blain, Professor of Environmental Medicine, University of
Newcastle, Consultant Physician, Newcastle Hospitals NHS Trust
and Director, Chemical Hazards and Poisons Division (North), Health
Protection Agency). The secretariat is jointly provided by DH
and the Food Standards Agency. DH lead for the COC.
3. Members of COC are appointed using procedures
set out by the Office of the Commissioner for Public Appointments.
All members have to fill in an annual declaration of interests
and also declare any interests in items discussed by COC. I have
no interests in the pesticide or agricultural industry.
4. The COC reports to the CMO for England
(Sir Liam Donaldson) and the chair of the Food Standards Agency
(Sir John Krebs). The COC's remit is to provide the best quality
scientific advice on carcinogens and approaches to risk assessment
of carcinogens. It has no regulatory function with regard to chemicals.
THE COC REVIEW
OF PROSTATE
CANCER
[Details of COC meetings, submitted papers and
minutes of meetings can be found on the COC internet site; http://www.advisorybodies.doh.gov.uk/coc/]
5. The COC first considered prostate cancer
during its horizon scanning exercise for 2003. Members were aware
of the evidence for an increase incidence of prostate cancer in
the UK and agreed to review the available published scientific
literature to evaluate the cause(s) for the observed increase.
6. Papers were prepared by the DH Toxicology
unit in consultation with the secretariat. Discussions were held
at the 6 November 2003, 1 April 2004, 24 June 2004, and 18 November
2004 meetings. The review papers were thorough and in my view
adequately covered the subject under discussion. A statement from
the Committee was agreed at the 18 November 2004 meeting subject
to chairman's action regarding a number of editorial changes identified
by members. The statement was finalised on 13 December 2004 and
placed on the COC internet site in early January 2005. As far
as I am aware this corresponded to the normal timescales for COC
work.
CONCLUSIONS REACHED
BY COC
7. I have listed the conclusions reached
by COC in full below:
(i) The increase in incidence of Prostate
Cancer reported over the past 2-3 decades is largely accounted
for by improved identification of cases due to increased numbers
of individuals undergoing surgery for benign prostatic conditions
and the use of prostate specific antigen.
(ii) The Committee concluded that there was
limited evidence to suggest an association between farmers/farm
workers, exposure to pesticides and increased risk of Prostate
Cancer. The possibility of such an association being causal could
not be discounted and the published literature should continue
to be monitored for further studies. Members commented on the
need for improved measures of exposure to pesticides and, in particular,
herbicides. It was considered that the potential association between
herbicide use by farmers and farm workers should be kept under
review.
(iii) The information from the available
epidemiological studies are consistent with the view that overall,
there is no convincing evidence of an increased risk of Prostate
Cancer in rubber workers as a whole.
(iv) There is no convincing evidence to associate
other occupations with Prostate Cancer.
(v) There is no convincing evidence to associate
occupational exposure to cadmium with cancer of the prostate.
The possibility that cadmium might induce androgen imbalance and
thus might potentially be associated with Prostate Cancer should
be monitored and relevant new information considered in the future.
(vi) The one available epidemiological study
on dietary zinc supplementation and risk of Prostate Cancer dose
found increased risk of Prostate Cancer at high levels of supplementation
(>100 mg/day). Further epidemiology studies are unlikely to
provide sufficient numbers of individuals regularly consuming
high doses of supplements for a study to be undertaken in the
UK. The Committee agreed that it could not identify a biologically
plausible rationale as to why zinc should be associated with Prostate
Cancer.
INTERPRETATION OF
CONCLUSION ON
FARMERS/FARM
WORKERS AND
PESTICIDES
8. The main conclusion reached by COC is
that the trend of increased incidence in prostate cancer is largely
due to changes/improvements in the diagnosis of prostate cancer
and treatment of benign prostatic conditions. This suggests that
no new environmental causes are required to account for the increased
incidence.
9. The committee did conclude, however,
that there was some evidence to suggest an association between
farming, farm workers exposure to pesticides and prostate cancer.
The overall magnitude of any association with pesticides is likely
to be small (see para 11 below) and it remains possible that factors
other than exposure to pesticides could be responsible for the
observed increased risk of prostate cancer in farmers and farm
workers Paragraphs 8 and 9 of the COC statement list a range of
risk factors which have been suggested for prostate cancer, (these
are reproduced at the end of this document for ease of reference).
There was insufficient evidence to reach a definite conclusion
on the epidemiological research regarding the cause(s) of the
reported association and there was no conclusive evidence to suggest
any particular occupational exposure of farmers and farm workers
to chemicals (including pesticides) which could be implicated.
There was some specific evidence implicating pesticide use but
this was insufficient to draw any definitive conclusions. In particular
the COC considered the meta-analysis* (systematic review by Van
Maele-Fabry and Willems (Occupational and Environmental Medicine,
60, 634-642., 2003) and the Canadian retrospective cohort study
by Morrison H, et al (American Journal of Epidemiology, 137, 270-280,
1993) in detail. These two studies provided considerable weight
of evidence for the conclusions reached by COC. Members felt that
the epidemiological literature on farmers and farm workers needed
to be kept under scrutiny.
[*A meta-analysis (or systematic review) is
a statistical analysis which combines the information from selected
studies. The quality of such an analysis is dependent on the quality
of the studies used.]
10. The Committee was aware that most of
the epidemiological approaches used required farmers/ farm workers
to recall their use of pesticides possibly several decades before
the onset of prostate cancer. Such approaches can be biased and
yield results that can be difficult to evaluate. Members therefore
felt that when further epidemiological research was undertaken,
it would be important to provide more accurate information on
the potential chemical exposures of farmers/farm workers than
in the studies completed to date. In this respect, I note that
there has been one reported novel approach for biological monitoring
of pesticides in epidemiological studies of prostate cancer (which
is cited in the COC statement in paragraph 17). Essentially the
authors found that serum organochlorine estimated exposure and
recall of exposure did not correlate. It is possible that biomonitoring
approaches could be developed but it would be important in the
first instance to develop appropriate hypotheses for study. It
is possible that the proposal from the ACP for a systematic review
of data from studies involving pesticide manufacturers could help
in this regard.
11. Thus the Committee felt there was some
evidence to associate employment as a farmer or farm worker and
use of pesticides with prostate cancer but the increased risk
of prostate cancer above the background incidence of prostate
cancer was likely to be small. The overall estimate of increased
risk from the meta-analysis (excluding proportional mortality
studies) for pesticide related occupations was 9% (95% confidence
interval 0-19%). Expressed another way this would increase the
likelihood of being diagnosed with prostate cancer from the current
UK figure of approximately 77 per 1,000 in the general population
to 84 per 1,000 among exposed men ie an additional seven cases
per 1,000 exposed. However, the uncertainty in this figure is
such that the number of additional cases per 1,000 exposed could
be between 0 and 14.
12. It was not possible to draw any conclusions
on which pesticides or groups of pesticides (eg herbicides or
fungicides) might be possibly implicated, although some limited
information from the Canadian study suggested an association with
exposure to herbicides. The Committee noted this observation was
based on an analysis of younger farmers in the Canadian study
(where mortality was followed from June 1971 up to the end of
1987) who were considered to have most likely applied the herbicides
themselves although the estimates of usage based on the Canadian
Agriculture census for 1971 would not provide accurate data on
cumulative exposure to herbicides. No conclusions could be reached
on the duration of any particular exposure which might be associated
with the increased risk of prostate cancer in farmers/farm workers.
13. The Committee reviewed a number of possible
mechanisms by which chemicals might induce prostate cancer but
did not reach any clear conclusions. For pesticides, this is most
likely due to the fact that the evidence for endocrine disrupting
effects of pesticides in-vivo was minimal and not convincing.
14. It is anticipated that any risks in
those living near to farms would be exceedingly small and not
measurable by any epidemiological techniques as exposures would
be predicted to be much lower than in individuals with occupational
exposure to pesticides.
15. The COC does not have any remit for
providing advice on the use of pesticides. This falls to the Independent
Advisory Committee on Pesticides (ACP). The ACP is the principle
source of advice to Government on the use of pesticides. I understand
that the ACP agreed some advice on possible research at its meeting
of the 13 January 2005 and recommended a meta-analysis of prostate
cancer among pesticide manufacturers. I am informed that Defra
have agreed to fund this work.
Professor David Forman
Centre for Epidemiology and Health Services Research,
University of Leeds
February 2005
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