Increasing parity is associated with a reduction in the risk of ovaria
n cancer, but it is not clear whether this association applies to diff
erent histopathological types and to borderline tumours. Moreover, the
temporal relations are poorly understood, and the possible role of ag
e at first birth remains unequivocal. We have investigated these issue
s in a case-control study nested in a nationwide cohort of women born
between 1925 and 1960 in Sweden. During follow-up until 1984, 3486 inv
asive ovarian cancers (2992 epithelial, 330 stromal, 149 germ-cell, 15
not classifiable) and 510 tumours of borderline malignant were diagno
sed. 5 individually age-matched (total 19 980) were selected for each
case woman. After simultaneous adjustment for parity and age at first
birth, increasing parity was associated with a pronounced consistent d
ecrease in relative risk of all invasive cancers (odds ratio for each
additional birth 0.81 [95% Cl 0.77-0.85]), epithelial cancer (0.81 [0.
77-0.86]), stromal cancer (0.84 [0.72-0.98]), and germ-cell cancer (0.
71 [0.48-1.05]), but a less consistent decrease for borderline tumours
(0.92 [0.81-1.04]). The risk of ovarian cancer decreased by about 10%
for each 5-year increment in age at first childbirth (odds ratios 0.8
9 [0.84-0.94] epithelial cancer, 0.92 [0.77-1.10] stromal cancer, 0.92
[0.65-1.32] germ-cell cancer, 0.93 [0.80-1.09] borderline tumours). B
ecause our findings cannot be readily explained by theories invoking i
ncessant ovulation or high serum concentrations of gonadotropins, new
aetiological hypotheses are needed. Pregnancy-dependent clearance from
the ovaries of cells that have undergone malignant transformation cou
ld explain the reproductive risk factors for ovarian cancer.