Abstract
For 50 years, the effect of age at first birth (AFB) has been thought to explain the strong association between breast cancer risk and age at first marriage (AFM), which was first reported in 1926. The independent effects of AFM, AFB and number of sexual partners adjusted for parity and other risk factors were estimated in reanalysis of a large international case-control study conducted in 1979 to 1982 (2274 breast cancers, 18209 controls) by unconditional logistic regression. Respective AFB and AFM breast cancer odds ratios (ORs) for ≥31 years relative to ≤18 years were 3.01 (95% CI 2.44-3.71; P(trend) < .0001) and 3.24 (95% CI 2.62-4.01; P(trend) < .0001) in univariate analyses. Among married parous women, these ORs fell to 1.38 (95% CI 0.98-1.95; P(trend) < .03) for AFB and 1.70 (95% CI 1.17-2.46; P(trend) < .002) for AFM when fitted together in multivariate analysis including other risk factors. A similar adjusted OR for AFM ≥ 31 years relative to ≤18 years was seen among married nulliparous women (OR 1.71, 95% CI 0.98-2.98; P(trend) < .001). AFM (a surrogate for age at starting prolonged cohabitation) is thus strongly associated with breast cancer risk. This suggests an effect of close contact. Identifying the (probably infective) mechanism might lead to effective prevention of breast cancer. The independent effect of AFB is smaller and could be due to residual confounding.
Highlights
Case-control studies by Lane-Claypon[1] and others[2, 3] reported a marked association of breast cancer risk with late age at first marriage (AFM), which at that time was a good surrogate for age at beginning cohabitation
The analyses in table 2, which are restricted to nulliparous women and adjusted for variables not related to childbirth, show a highly significant trend with increasing AFM in married nulliparous women (p(trend)
Effect estimates for each variable among unmarried parous women (29 cases, 262 controls) were consistent with the estimates unadjusted for AFM among married parous women but were very imprecise due to small numbers and are uninformative on the joint effects of AFM and at first birth (AFB)
Summary
Case-control studies by Lane-Claypon[1] and others[2, 3] reported a marked association of breast cancer risk with late age at first marriage (AFM), which at that time was a good surrogate for age at beginning cohabitation. This was investigated in 1970 in the Seven Country Study (SCS)[4] by MacMahon and colleagues, who concluded that the apparent effect of AFM was entirely due to its strong correlation with age at first birth (AFB).
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