PGL-EXPO feasibility study of exposure to SDHi fungicides and risk of hereditary SDHx paraganglioma or pheochromocytoma.

Paraganglioma and pheochromocytoma (PPGL) are rare neuroendocrine tumors with a strong genetic component. SDHx genes are well-known PPGL susceptibility genes. A role of environmental factors, such as succinate dehydrogenase inhibitor (SDHi) fungicides, is suspected in PPGL tumorigenesis. We evaluated the feasibility of a case-control study investigating the association between pesticides, focusing on SDHi fungicides, and the risk of SDHx-related PPGL. The study was conducted in a single referral center between March and June 2022. Cases were patients with PPGL and an SDHx germline mutation diagnosed between 2000 and 2021. Controls, were selected among relatives of cases, diagnosed as SDHx mutation carriers by a presymptomatic genetic test and without PPGL after tumor screening tests. A matching process was formulated to prioritize cases and controls that could be matched according to date of birth, type of gene mutated and distinct family. Phone interviews were used to collect data on general characteristics, PPGL risk factors, the domestic use of pesticides, residential history, occupational history. Addresses were geocoded. The presence of crops within a buffer of 1,500 m was estimated for residential addresses at diagnosis. The probability of occupational exposures to SDHi fungicides was assessed based on the French crop-exposure matrix PESTIMAT. An information letter was sent to 138 subjects out of the 193 followed-up by the center. The prioritization of recruitment was defined by the matching potential of each subject. Overall, 110 subjects were reached by phone, 101 accepted to be included, and 42 cases and 40 controls were interviewed (response rate: 81%). Missing data on domestic exposure to pesticides were more frequent for the households most back-in-time. Even for the oldest residential addresses, at least 81% of the addresses had a precise geocoding. In a buffer with a radius of 1500 m, arable land was present for 55% of subjects' addresses, vineyards and orchards for 5% and 3.8% respectively. Two subjects might have been exposed to SDHi fungicides in the occupational context. Our study showed high participation and response rates. Exposure to pesticides could be assessed with moderate to good precision, even for exposures far back in time.