The curvilinear relationships between grand parity and incidence of hormone-dependent cancers; follow-up of postmenopausal women in the Norwegian 1960 Census


Breast, ovarian and endometrial cancers are named hormone dependent cancers (HDC) because of the effects of endogenous hormones, including parity, on the incidence rates. Here, we will test the hypothesis that each additional child has the same relative preventive effect on the risk of each of the three cancer sites and with similar shapes of the incidence curves over the extended exposure range, 1 - 18 children in postmenopausal women.

The study is based on parity information from the Norwegian 1960 Census for women aged 45-89 years. A total of 385 816 married women answered the question of number of children in present marriage to a civil servant. Follow-up continued until the first of any of the HDC diagnosis, death, or end of follow-up 2005 through linkages based on the unique Norwegian birth number. Included were 16 905 breast cancers, 3 827 ovarian cancers and 3 834 endometrial cancers. Based on person-years (PY), the percentage change in incidence rates of the three cancer sites for each additional child was calculated using a logit regression model including models with higher order terms. A new statistical method for analyses of collinearity between parity and age at first birth has been developed. Age at marriage was used as a proxy for age at first birth.
Parity had strong linear effects on the incidence rates for all three cancer sites (p<2e-16). The percentage decrease for each of the cancer diagnosis for an additional child were for breast cancer 10.5% (95% CI; 9.6-11.4), ovarian cancer 13.2% (11.2-15.3) and endometrial cancer 10.9% (8.9-12.8) with similar curvilinear relationship. Models with higher order terms gave slightly better fit to the data with a stronger protective effect for increasing parity on ovarian cancers, while for breast cancer age became more important. Combining the incidence of all three cancers gave a percentage decrease for each additional child of 11.0% (10.1-11.8). The risk for HDC cancer was reduced with earlier age at marriage (first birth) for women with 1-2 children for breast cancer and ovarian cancer and 1 child for endometrial cancer, but the effect was smaller than one additional child. Age of the women at marriage was not significant for the sum of the three cancers. The study demonstrated the strong, regular protective effect of each additional child or full-term pregnancy on the incidence rates of the hormone-dependent cancers throughout the exposure range and with similar curvilinear relations. Reduced fertility is a common, strong etiological factor for the three hormone-dependent cancers in postmenopausal women. These findings support a hypothesis that similar immunological changes during each pregnancy could be the biological explanation.