Coste Astrid, Buffet Alexandre, Duboeuf Margaux, Boudif Sabrina, Grassot Lény, Ouelaa Boutheina, Sueur Annabelle, Lounis Timgad, Pérol Olivia, Fervers Béatrice, Roqueplo Anne-Paule Gimenez
Department of Prevention Cancer Environment, Centre Léon Bérard, Lyon, France.
Inserm U1296 Radiation: Defense, Health, Environment, Lyon, France.
Sci Rep. 2025 Jul 2;15(1):22716. doi: 10.1038/s41598-025-09166-w.
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.
副神经节瘤和嗜铬细胞瘤（PPGL）是罕见的神经内分泌肿瘤，具有很强的遗传成分。SDHx基因是众所周知的PPGL易感基因。人们怀疑环境因素，如琥珀酸脱氢酶抑制剂（SDHi）杀菌剂，在PPGL肿瘤发生中起作用。我们评估了一项病例对照研究的可行性，该研究调查了以SDHi杀菌剂为重点的农药与SDHx相关PPGL风险之间的关联。该研究于2022年3月至6月在一个单一的转诊中心进行。病例为2000年至2021年间诊断出患有PPGL且携带SDHx种系突变的患者。对照是从病例的亲属中挑选出来的，通过症状前基因检测被诊断为SDHx突变携带者，且在肿瘤筛查检测后未患PPGL。制定了一个匹配程序，以优先选择可根据出生日期、突变基因类型和不同家族进行匹配的病例和对照。通过电话访谈收集一般特征、PPGL危险因素、家庭农药使用情况、居住史、职业史等数据。对地址进行了地理编码。估计了诊断时居住地址周围1500米缓冲区内的作物情况。根据法国作物接触矩阵PESTIMAT评估职业接触SDHi杀菌剂的可能性。该中心对193名随访对象中的138名发送了信息信。招募的优先级由每个对象的匹配潜力决定。总体而言，通过电话联系到了110名对象，101名同意纳入，42例病例和40名对照接受了访谈（回复率：81%）。家庭农药接触的缺失数据在时间上最久远的家庭中更为常见。即使是最古老的居住地址，至少81%的地址有精确的地理编码。在半径为1500米的缓冲区内，55%的对象地址有耕地，葡萄园和果园分别占5%和3.8%。两名对象可能在职业环境中接触过SDHi杀菌剂。我们的研究显示出较高的参与率和回复率。即使是对时间久远的接触，也能以中等至良好的精度评估农药接触情况。
