Aryl hydrocarbon receptor-interacting protein and pituitary adenomas: a population-based study on subjects exposed to dioxin after the Seveso, Italy, accident.
OBJECTIVE
The pathogenesis of sporadic pituitary tumors is unknown. Loss-of-function mutations of aryl hydrocarbon receptor-interacting protein (AIP) have been identified in patients with familial pituitary tumors. AIP is a chaperone protein with multifunction properties, including modulation of the transcriptional activity of the aryl hydrocarbon receptor, which mediates toxicological and carcinogenic dioxin effects.


METHODS
We investigated the incidence of pituitary tumors in the Seveso population exposed to 2,3,7,8-tetrachlorodibenzo-para-dioxin following an industrial accident in 1976.


METHODS
Through the hospital discharge registration system of Lombardy Region, we identified incident cases of pituitary adenomas between 1976 and 1996 in the Seveso population, subdivided in zone A (n=804), B (n=5.941), and R (n=38.624) according to high, intermediate, and low exposure to dioxin respectively, and in the surrounding non-contaminated area, as reference (n=232 745).


RESULTS
We identified 42 pituitary adenomas in the reference area, 1 prolactinoma in zone A (rate ratio (RR) 6.2; 95% CI 0.9-45.5, P=0.07), 2 nonfuctioning pituitary tumors (NFPAs) in zone B (RR 1.9; 95% CI 0.5-7.7, P=0.39), and 3 prolactinomas and 2 NFPAs in zone R (RR 0.7; 95% CI 0.3-1.8, P=0.48).


CONCLUSIONS
The study is unique with regard to the availability of epidemiological and clinical data in an area of relatively pure dioxin exposure. The study indicates no statistically significant increase of incident pituitary tumors in this area, although the tendency toward a higher risk (three cases in zones A and B) of pituitary tumors in subjects exposed to high-intermediate dioxin concentrations in comparison with nonexposed population suggests the need for extended follow-up.
Pesatori
Angela Cecilia
AC
Department of Occupational and Environmental Health, EPOCA Research Center, Clinica L Devoto, University of Milan, Via San Barnaba 8, 20122 Milano, Italy. angela.pesatori@uninimi.it
Baccarelli
Andrea
A
Consonni
Dario
D
Lania
Andrea
A
Beck-Peccoz
Paolo
P
Bertazzi
Pier Alberto
PA
Spada
Anna
A
D000062:Accidents, Occupational; D000236:Adenoma / Q000139:chemically induced / Q000453:epidemiology* / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D004147:Dioxins / Q000506:poisoning*; D004781:Environmental Exposure / Q000009:adverse effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D007558:Italy / Q000453:epidemiology; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000139:chemically induced / Q000453:epidemiology* / Q000235:genetics; D011159:Population Surveillance / Q000379:methods; D012989:Soil Pollutants / Q000506:poisoning; D055815:Young Adult
D004147:Dioxins; D047908:Intracellular Signaling Peptides and Proteins; D012989:Soil Pollutants; C103265:aryl hydrocarbon receptor-interacting protein