Between June 1981 and March 1983, data were collected to assess risk factors for gestational trophoblastic disease in a case-control study of 100 women with trophoblastic tumors (17 partial hydatidiform moles, 63 complete moles, and 20 choriocarcinomas) and 200 age-matched controls admitted for normal deliveries to university or general hospitals in Lombardy, Northern Italy. Questions were asked about each patient's general life-style, and medical, obstetric, menstrual, contraceptive, and social history. The risk of trophoblastic disease increased with increasing paternal age: women whose husbands were aged 40-44 years and 45 years or more had a relative risk of 2.4 and 4.2, respectively, compared to women married to men aged under 40 years. This association was independent of maternal age. Cigarette smoking was associated with trophoblastic tumors (relative risk estimate for smokers vs. never smokers = 2.0, 95% confidence interval = 1.2-3.2), the risk being greater for women who smoked more cigarettes and for longer. The effect of cigarette smoking was not explained by any other identified potential distorting factor. A positive history of fertility problems or difficulties in conception and a personal or family history of gestational trophoblastic disease were more common among the cases. Past use of oral contraceptives was not related to the risk of trophoblastic tumors, but use of an intrauterine device was significantly more common among the cases. The findings give epidemiologic support to the evidence of an androgenetic role in the origin of hydatidiform mole; moreover, they provide new hypotheses on the risk factors for gestational trophoblastic disease in developed countries. Further exploration of these factors may lead to a more coherent body of evidence on the etiology of these diseases.
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