MCR, C Samanic, M Dosemecil, J Lubin, R Tarone, CF Lynch, C Knott,
K Thomas, JA Hoppin, J Barker, J Coble, DP Sandler and A Blair.
2003. Use of Agricultural Pesticides and Prostate Cancer
Risk in the Agricultural Health Study Cohort. American
Journal of Epidemiology 157:800–814.
a series of previous studies, farming has been the single most consistent
occupational risk factor for development of prostate
cancer. In this study, Alavanja et al. strengthen that
link by documenting a small but significant increase in
prostate cancer risk for pesticide applicators, including farmers.
Their research found that use of organochlorine pesticides and methyl
bromide elevated prostate cancer risk for the entire cohort, and
that several other pesticides elevated risk for men with a family
history of prostate cancer.
did they do? Alavanja et al. examined the relationship
between exposure and response for 45 important agricultural chemicals
and prostate cancer. Their data came from the Agriculture
Health Study cohort: 55,332 pesticide applicators (commercial
and private) recruited in Iowa and North Carolina 1993-1997.
in the Agriculture Health Study were surveyed to determine uses
of 50 different pesticides, methods of application, crops grown,
nonfarm occupational exposure, family medical history, plus status
of a series of potential confounding variables, such as smoking,
alcohol consumption and involvement in engine repair (which results
in solvent exposure).
et al. used a variety of approaches to characterize each
study participant's history of pesticide exposure, ranging from
assessment of the frequency and intensity of exposure to each compound
one-by-one, to a statistical characterization, called "factor
analysis," that identified groups
that tended to be used together and allowed each study subject to
be ranked on the intensity of exposure to these co-occurring groups
prostate cancer diagnoses prior to enrollment in the study were
excluded from the analysis.
condition through 1999 was then determined by examining medical
records. Over 98% of the cohort was included in the analysis.
a baseline for comparison, Alavanja et al. used the overall
rate of prostate cancer in men living in Iowa and North Carolina,
adjusted for race, age and the period of observation (1994-1998).
did they find? Not surprisingly, prostate cancer risk was
higher in older men and in men from families with a history of prostate
pesticide applicators to baselines in North Carolina and Iowa, Alavanja
et al. noted a small but significant excess in prostate
cancer cases in the pesticide applicators: During the period of
observation (1994-1998), 566 new prostate cancer cases were detected
within the study population. This is 14% more than would have been
expected based on the average overall incidence of prostate cancer
(495 cases), or an odds ratio of 1.14. The incidence rate was higher
compared to baseline in commercial
(41% greater) than among private
clearest pattern linking pesticide exposure to prostate cancer risk
was for the fumigant methyl bromide. Applicators with the
highest levels of exposure to methyl bromide were more likely to
develop prostate cancer. For those applicators in the most heavily
exposed group (the top 20%), the odds ratio was 3.47.
association with methyl bromide was observed in an analysis of the
total sample, as well in separate analyses of North Carolina and
Iowa pesticide applicators and within private and commercial applicators.
the analysis of groups of co-occurring pesticides (see above), the
only significant pattern to emerge was that men who had used an
older suite of chlorinated
were at greater risk to prostate cancer.
also suggested that men from families with a history of prostate
cancer were at greater risk following exposure to certain pesticides,
including chlorpyrifos, coumaphos, permethrin and butylate. According
to the authors, this suggests that familial genes or a shared familial
environmental background may increase susceptibility to the effects
of pesticides on prostate cancer risk.
does it mean? Alavanja et al. find a small but
significant increase in prostate cancer risk among pesticide applicators
in Iowa and North Carolina. This finding is consistent with prior
studies on prostate cancer in farmers.
of the principal strengths of the study was its very large sample
size, which allowed confirmation of relatively small effects.
an unavoidable weakness was using subject recall of exposures, some
of which, in the oldest members of the cohort, would have been based
on decades-old memories. In this regard, it is important to note
that failures and error in recall would almost certainly hide associations
rather than create them, i.e., bias the results toward false
negatives and lead to a lowering of the estimate of the odds
from analysis those with diagnosed cases of prostate cancer prior
to enrollment may also have shifted the odds ratio downward. That
would be the case, for example, if one effect of pesticide exposure
was to hurry development of the disease in a subset of the population.