Agricultural exposure and risk of ovarian cancer in the AGRIculture and CANcer (AGRICAN) cohort.

BACKGROUND: Ovarian cancer is rare with a poor prognosis and few established risk factors. Hormones and reproductive factors significantly impact its development, suggesting a potential link with endocrine disrupters. METHODS: In the AGRICAN cohort, 59 391 female farmers completed data on lifelong agricultural exposures and reproductive life. Cox models with attained age as timescale (HR and 95% CI) were used. The role of hormonal factors as potential confounders was considered along with specific time windows for exposure (childhood, puberty and menopause). Female farmers were the reference group (for the principal analyses). RESULTS: Between enrolment (2005-2007) and the end of follow-up (31 December 2017), 262 incident ovarian cancers were identified. An increased risk was observed for females involved in pigs (HR=2.12 (95% CI 1.27 to 3.52)) including during puberty (HR=1.83 (95% CI 1.13 to 2.94)), fruit-growing (HR=2.17 (95% CI 1.09 to 4.30)) and potato seed treatment (HR=2.81 (95% CI 1.29 to 6.09)). Conversely, females born on farms growing grain cereals (HR=0.64 (95% CI 0.46 to 0.90)) or pig-breeding (HR=0.78 (95% CI 0.55 to 1.12)) presented a reduced risk of ovarian cancer. Triazine herbicide exposure was not associated with ovarian cancer. The effect of agricultural exposures remained unchanged in multivariate models considering contraception, parity, puberty age, menopause age and body mass index. CONCLUSION: This study is the first to assess the association between specific agricultural exposures and ovarian cancer comprehensively. Some of the positive associations observed suggest that some pesticide exposure (especially during puberty) could play a role in the development of ovarian cancer. On the other hand, agricultural exposure during early life could have a protective effect, as observed for lung cancer among farmers. Finally, we did not confirm the previous putative effect of exposure to triazine herbicides.

Agricultural exposure and risk of soft tissue sarcomas and gastrointestinal stromal sarcoma in the AGRIculture and CANcer (AGRICAN) cohort.

Sarcomas are a heterogeneous group of tumors whose incidence is nearly 5 per 100 000 inhabitants in Europe. Their causes are poorly understood, although occupational exposures (especially farming and pesticides) are suspected. The AGRICAN cohort is a prospective study of 181 842 individuals enrolled in 2005 to 2007 who completed an enrolment questionnaire with data on lifelong agricultural exposure. Associations between agricultural exposure and sarcoma overall, gastrointestinal stromal tumors (GIST) and myomatous and fibrous sarcoma together, were analyzed with a Cox model. Until 2015, 188 incident cases of sarcoma were identified. Increased risks were observed (a) among cattle farmers working <10 years (HR<10years  = 2.45, 95% CI 1.36-4.43) and breeding ≥50 livestock (HR≥50animals  = 3.84, 95% CI 1.60-9.22), especially if involved in animal care and building disinfection, (b) in greenhouse production (HR = 1.82, 95% CI 1.01-3.30) and (c) in field-grown vegetable production (HR = 1.49, 95% CI 0.96-2.32). Concerning histological subtypes, GIST were positively associated with pesticide use in vineyards (HR = 2.24, 95% CI 0.95-5.30). For myomatous and fibrous sarcoma, the only increase was seen in field-grown vegetable production (HR = 2.37, 95% CI 1.16-4.85). In AGRICAN, the risk of sarcomas was increased in several farming activities with differences according to histological subtype.

Agriculture Exposure and Time to Pregnancy Among Women Enrolled in the French Prospective Cohort AGRICAN.

OBJECTIVES: In few retrospective studies, prolonged time-to-pregnancy (TTP) was observed for women exposed to pesticides especially in flower production. The present study investigated time-to-pregnancy in the AGRICAN cohort. METHODS: Analyses were performed on 616 women reporting a pregnancy (2005 to 2017), and data on agricultural activities performed before the last pregnancy was retrospectively collected. Fecundability odds ratios (fOR) were estimated using a discrete time analogue of Cox proportional hazard model adjusted on maternal and paternal age, body mass index (BMI), and alcohol consumption. RESULTS: A decrease in fecundability was non-significantly associated with farm work (adjusted fOR = 0.86; 95% confidence interval [CI]: 0.71 to 1.05). Decreases were also observed for nightwork (afOR = 0.75; 95% CI: 0.49 to 1.15) and exposure to vibrations (afOR = 0.68; 95% CI: 0.43 to 1.09). CONCLUSION: Women working on a farm before conception appeared to experience a longer TTP. Negative associations were suggested for some agricultural activities and working conditions.

Occupational exposure to pesticides and multiple myeloma in the AGRICAN cohort.

PURPOSE: Epidemiological studies have found an increased risk of multiple myeloma (MM) in farmers. Few studies have investigated the detailed circumstances of occupational pesticide exposure which could explain these increased risks (pesticide use on crops, seeds or on animals, contact with treated crops) and the role of other exposures. In the Agriculture and Cancer cohort (AGRICAN), we assessed the associations between MM and crop- or animal-related activities, with specific attention to pesticide exposure via use on animals and crops or contact with treated crops and to disinfectant exposure. METHODS: Analyses concerned 155,192 participants, including 269 incident MM identified by cancer registries from enrolment (2005-2007) to 2013. Cox models using attained age as time scale were run to calculate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: MM risk was increased in farmers (i) who started using pesticides on crops in the 1960s, especially among those applying pesticides on corn (≥ 20 years: HR 1.73, 95% CI 1.08, 2.78, p for trend < 0.01) and (ii) using insecticides on animals (HR 1.48, 95% CI 1.11, 1.98), especially among horse farmers (≥ 10 years: HR 2.77, 95% CI 1.22-6.27, p for trend = 0.01). We also observed significant elevated risks with disinfectant use in animal barns. CONCLUSIONS: Findings support the role of pesticide use on crops and animals in the occurrence of MM risk in farmers.

Agricultural exposures to carbamate herbicides and fungicides and central nervous system tumour incidence in the cohort AGRICAN.

BACKGROUND: Pesticides exposures could be implicated in the excess of Central Nervous System (CNS) tumors observed in farmers, but evidence concerning individual pesticides remains limited. Carbamate derivative pesticides, including herbicides and fungicides (i.e. (thio/dithio)-carbamates), have shown evidence of carcinogenicity in experimental studies in animals. In the French AGRICAN cohort, we assessed the associations between potential exposures to carbamate herbicides and fungicides and the incidence of CNS tumors, overall and by histological subtype. METHODS: AGRICAN enrolled 181,842 participants involved in agriculture. Incident CNS tumors were identified by linkage with cancer registries from enrollment (2005-2007) until 2013. Individual exposures were assessed by combining information on lifetime periods of pesticide use on crops and the French crop-exposure matrix PESTIMAT, for each of the 14 carbamate and thiocarbamate herbicides and the 16 carbamate and dithiocarbamate fungicides registered in France since 1950. Associations were estimated using proportional hazard models with age as the underlying timescale, adjusting for gender, educational level and smoking. RESULTS: During an average follow-up of 6.9 years, 381 incident cases of CNS tumors occurred, including 164 gliomas and 134 meningiomas. Analyses showed increased risks of CNS tumors with overall exposure to carbamate fungicides (Hazard Ratio, HR = 1.88; 95% CI: 1.27-2.79) and, to a lesser extent, to carbamate herbicides (HR = 1.44; 95% CI: 0.94-2.22). Positive associations were observed with specific carbamates, including some fungicides (mancozeb, maneb, metiram) and herbicides (chlorpropham, propham, diallate) already suspected of being carcinogens in humans. CONCLUSIONS: Although some associations need to be corroborate in further studies and should be interpreted cautiously, these findings provide additional carcinogenicity evidence for several carbamate fungicides and herbicides.

Digestive and genitourinary sequelae in rectal cancer survivors and their impact on health-related quality of life: Outcome of a high-resolution population-based study.

BACKGROUND: With the rising number of rectal cancer survivors, more patients with sphincter-preserving surgery are having to live with a potentially impaired quality of life. The survey aimed to assess bowel and genitourinary sequelae and their impact on quality of life in an unselected registry-based population of rectal cancer survivors. METHODS: This cross-sectional cohort survey (registered at ClinicalTrials.gov; ID: NCT03459235) included patients with rectal cancer who underwent curative surgery with sphincter-preserving surgery from January 1, 2007 to January 31, 2015. Patients with recurrent disease, intestinal stoma, or cognitive disorders were excluded. Validated scoring system included the Urinary Symptom Profile in women and the International Prostate Symptom Score in men for urinary function, International Index for Erectile Function 5 in men and Female Sexual Function Index in women for sexual function, and Core 30/ Colo Rectal 29 questionnaires for quality of life and Low Anterior Resection Syndrome score for bowel function. The impact of functional sequelae on global quality of life was evaluated by multiple linear regression. RESULTS: Responders (45.3%, 92/203 patients) and nonresponders were comparable according to sex, age, tumor stage, and neoadjuvant chemoradiation. With a mean follow-up of 6.5 years, 65.2% of the rectal cancer survivors had bowel dysfunction, of whom 41.3% experienced major Low Anterior Resection Syndrome and 80% of rectal cancer survivors experienced genitourinary dysfunction. In multiple linear regression, poor bowel function was a significant predictor of global quality of life in men (P = .04) and women (P = .0003). CONCLUSION: This survey highlights the importance of sexual and bowel dysfunction in rectal cancer survivors and the strong correlation between high Low Anterior Resection Syndrome score and inferior quality of life. Further studies are needed to improve knowledge on how to predict bowel dysfunction and how to best support patients with bowel dysfunction.