The relationship of gestational trophoblastic disease (GTD) to parental age was evaluated in a case-control study of 132 women with hydatidiform mole (108) or choriocarcinoma (24) and 304 control subjects hospitalized for normal deliveries. Cases and controls were recruited in Lombardy (Northern Italy), and all were white and Italian. Compared to the risk of developing trophoblastic tumors in women 21-35 years old, the risk of developing trophoblastic tumors was elevated both in younger [less than or equal to 20 yr old, relative risk (RR) = 1.4, with 95% confidence interval (Cl) of 0.7-2.8] and in older subjects, RR being 1.2 (95% Cl 0.7-2.8) and 5.2 (95% Cl 2.2-12.3) for women 36-40 years old and over 40, respectively. The risk estimates for the last two categories were reduced to 0.7 (with 95% Cl of 0.3-1.9) and 2.5 (with 95% Cl of 0.7-8.9) when adjustment was made for paternal age by means of the Mantel-Haenszel procedure. Higher paternal age also was associated with GTD: Women whose husbands were 41-45 years old and over 45 had RR of 1.6 (with 95% Cl = 0.7-3.7) and 4.9 (with 95% Cl = 2.2-11.1), respectively, compared to women married to men less than 40 years old. These risk estimates were practically unchanged when adjustment was made for the woman's age. Examination of the effects of parental and maternal ages suggests that the highest risk estimate was observed when both parents were older. The findings of the present study were consistent with increased risk in the youngest maternal age group and confirm that older maternal age is associated with increased risk of GTD. Furthermore, showing a strong, independent effect of paternal age, they give epidemiologic support to the cytogenetic evidence of an androgenetic role in the origin of GTD.
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