| Summary: | Eiliv Lund,1,2 Aurelie Nakamura,3,4 Igor Snapkov,1 Jean-Christophe Thalabard,5 Karina Standahl Olsen,1 Lars Holden,6 Marit Holden6 1Department of Community Medicine, UiT The Arctic University of Norway, Tromso, Norway; 2The Cancer Registry of Norway, Oslo, Norway; 3Department of Social Epidemiology, Pierre Louis Institute of Epidemiology and Public Health, Sorbonne University, INSERM, Paris, France; 4French School of Public Health (EHESP), Doctoral Network, Rennes, France; 5MAP5, UMR CNRS 8145, Université Paris Descartes, Sorbonne Paris Cite, Paris, France; 6Norwegian Computing Center, Oslo, Norway Background: There is a large body of evidence demonstrating long-lasting protective effect of each full-term pregnancy (FTP) on the development of breast cancer (BC) later in life, a phenomenon that could be related to both hormonal and immunological changes during pregnancies. In this work, we studied the pregnancy-associated differences in peripheral blood gene expression profiles between healthy women and women diagnosed with BC in a prospective design. Methods: Using an integrated system epidemiology approach, we modeled BC incidence as a function of parity in the Norwegian Women and Cancer (NOWAC) cohort (165,000 women) and then tested the resulting mathematical model using gene expression profiles in blood in a nested case–control study (460 invasive case–control pairs) of women from the NOWAC postgenome cohort. Lastly, we undertook a gene set enrichment analysis for immunological gene sets. Results: A linear trend fitted the dataset precisely showing an 8% decrease in risk of BC for each FTP, independent of stratification on other risk factors and lasting for decades after a woman’s last FTP. Women with six children demonstrated 48% reduction in the incidence of BC compared to nulliparous. When we looked at gene expression, we found that 756 genes showed linear trends in cancer-free controls (false discovery rate [FDR] 5%), but this was not the case for any of the genes in BC cases. Gene set enrichment analysis ...
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