In a study conducted in Gironde, France, no significant increase in the risk of brain cancer was seen when no versus any occupational exposure to pesticides was considered. However, a significant increase was observed among the most exposed subjects (OR
2.16, 95% CI 1.10 to 4.23). A 47% non‐statistically significant increase in risk was observed when gliomas were considered separately, becoming significant in the most exposed subjects (OR
3.21, 95% CI 1.13 to 9.11). We also found an increased risk of brain tumour for subjects treating house plants (OR
2.24, 95% CI 1.16 to 4.30).
Our population‐based case–control study is one of the largest specifically exploring the role of occupational and environmental pesticides. The participation rate in the study was high, but non‐participating cases were older and more frequently presented gliomas or lymphomas than the participating cases. Elderly people might have been more frequently exposed to pesticides as the part played by agriculture was greater in previous decades in France. Their underparticipation would decrease our risk estimates. The lower participation of subjects with gliomas and lymphomas would have the same impact if we consider that the higher risks were observed for these histological types.
Our study design enabled accurate data on pesticide use to be obtained but did not provide information about the specific pesticides responsible. Unfortunately, because of trade interests, information on the use of specific pesticides in a given area is not available in France. The reliability of farmers' pesticide use report is debatable as the number of pesticides used in vineyards is large, approaching 20 in a single treatment period, and an even larger number during a farmer's whole life Moreover, the brain injury and memory impairment of some of the subjects precluded asking for accurate details of pesticide names. This is why pesticide assessment relied on expertise. However, because interviewers were not blinded to the disease status, it might be argued that they probed more deeply into the exposure of cases than of controls. This bias was minimised by using well‐trained interviewers, a standardised questionnaire and by the fact that the distribution of subjects among interviewers was not dependent on the case–control status.
However the index exposure we used has some limitations: it is a generic index, not taking into account differences between classes of pesticides (formulation, volatility, dermal penetration, etc) specificities of use like the type of equipment, the duration of the treatment days, the use of protective equipment, etc. Our approach only enables us to differentiate between users and non‐users, and to rank users according to their frequency and duration of use to different gradients of pesticide exposure.
- This case–control study demonstrates an increase in the risk of brain tumour in farmers, especially for gliomas and for the highest occupational exposures.
- A trend was also seen for treatment of home plants, but this result requires replication.
More than 70% of exposed cases in the highest quartile were exposed in the years 1965 to 1985 and half of them or fewer were exposed before 1950 or after 1985. Therefore, if the association we observed is genuine, it might be suggested that the exposure leading to the occurrence of brain tumour may be the pesticides used in the 1965–85 period. In vineyards, pests controlled by the majority of pesticide applications are fungi such as mildew, black‐rot and oidium. In this time period, inorganic substances (copper, sulphur), dithiocarbamates (mancozeb, mancopper, maneb, propineb, zineb) and phthalimides (captafol, folpet, captan) were recommended for use on these fungi.
After 5.3 years of follow‐up, no increase in the brain cancer incidence and mortality was observed in the Agricultural Health Study cohort (private applicators, commercial applicators, spouses of private applicators) in comparison with those of the general population of Iowa and North Carolina.16,17
But the numbers of brain cancer cases may increase with the follow‐up. Further analysis will be possible taking into account exposures and confounders. Our results are in accordance with the ecological study by Viel et al
, who found that mortality from brain cancer was significantly higher in areas planted with vines.18
Our results are also consistent with the study by Musicco et al
in Italy, who found an increase in the risk of glioma for farmers, especially for those using chemicals (RR
1.6, 95% CI 1.06 to 2.42).19
This study could not dissociate the role of specific families of pesticides, but the use of “insecticides and fungicides” considered together was associated with a significant increase in risk (RR
2.0, 95% CI 1.22 to 3.23). No consistent trend was found with duration of exposure, but the level of exposure was not assessed. The consistency between Musicco's results and our own study is of particular interest, because both regions are predominantly involved in viniculture.
- Better understanding of pesticide exposures in farmers is needed to improve prevention.
- Additional studies in other agricultural settings and on pesticide home exposure are needed to confirm these results.
Consumption of aspartame was associated with a decrease in risk. The role of aspartame in brain tumour was suggested from equivocal experimental studies dealing with its carcinogen effects on rodent brain and from the observation that aspartame might be metabolised in nitrosurea‐like molecule. From an epidemiological perspective, only one ecological study examined the question,20
but could not reach definitive conclusions. Treatment of house plants was also associated with an increase in risk of brain tumour. The question about such exposure was rather limited in our study and recall bias cannot be ruled out. This is why this subject warrants further research, because exposure to pesticides for such purposes is acknowledged to be far lower than in agricultural settings, and because similar results have never been reported in previous studies. None of the other measures collected in our study appeared to be related to this variable or could signify a confounding effect. It is not completely clear what types of pesticide are being, and have been, sold in the past for use on house plants, but as the general population does not easily identify specific pests, “total treatment” (insecticides and fungicides) are commonly purchased. It is a matter of concern that they are sprayed in closed dwellings and that they are recommended for use every week. As in our study, treatment of house plants was mainly by women in urban surroundings, we cannot rule out the role of certain characteristics of this population, which were not explored in our study, such as lifestyle including diet, or domestic exposure to other chemicals.
Living in a rural area tended to be associated with a decrease in risk. Even if not significant, this result could appear inconsistent with the close relationship between “agriculture” and “rural setting”. However, 60.7% of subjects in rural settings were not classified as being occupationally exposed to pesticides in our study. The lower risk in rural areas, together with the slight decrease for subjects living in a district planted with vineyards, does not favour a role of environmental exposure to pesticides near treated areas in the occurrence of brain tumours. This is not consistent with the study by Aschengrau et al
, who found an association between residence near cranberry bog fields and the risk of astrocytomas (OR
6.7; 95% CI 1.6 to 27.8).21
Ahlbom et al
also found that having lived in the vicinity of a farm increased the risk of astrocytoma (OR
1.7, 95%CI 1.0 to 2.8), but no detail was given on what was meant by “vicinity” and on the type of agricultural setting.22
In conclusion, our study supports the role of pesticides in brain tumours but only for high levels of occupational exposure, in treatment tasks and also in re‐entry conditions, in an agricultural setting where fungicides are predominantly used. Further studies on larger samples are needed to determine if the risk is more specifically associated with gliomas, and to investigate a possible association with specific families of pesticides. A higher risk for gliomas, the histological subtype consistently more common in men than in women, would suggest that differences in occupational exposure between men and women could contribute to the differences in rates between them. In addition, the treatment of house plants seemed to be associated with the risk of brain tumours, although it was not possible to determine the role of other factors in the domestic setting.