Reduced breast cancer risk after remarriage: evidence of genetic-immune protection

Several reproductive factors have been found to be associated with breast cancer. Based on an immunologic rather than strictly hormonal interpretation of these observations, we hypothesized that, beyond the observed associations relating to pregnancy per se, multiple marriages would be found to protect women against breast cancer. We obtained cases and controls from linked records from the Utah Cancer Registry and genealogic records. A total of 2,414 women with newly diagnosed breast cancer and 9,138 individually matched controls were included. The unadjusted odds ratio for each marriage after the first was 0.81 [95% confidence interval (CI) = 0.68-0.97]. After adjustment for major reproductive factors, multiple marriages were still found to reduce the risk of breast cancer (odds ratio = 0.86; 95% CI = 0.72-1.03). The findings are consistent with the operation of an immunologic mechanism in the etiology of breast cancer and suggest that the gene/antigen responsible for this effect is quite common in males. Further empirical evaluation of the fetal antigen hypothesis seems warranted.