No impact of parity on global gene expression levels in breast cancer tissue and normal breast tissue – a nested case-control study in the Norwegian Women and Cancer study

Abstract Background We have previously demonstrated that the linear decrease in postmenopausal breast cancer incidence with increasing parity is linked to expression changes in hundreds of genes in the peripheral blood cells of healthy women. However, these changes are not observed in the blood cells of cancer patients. In this study, we conducted a comparative analysis of global gene expression profiles in normal breast tissue and breast cancer tissue, with a focus on parity as the explanatory variable. Methods The Norwegian Women and Cancer (NOWAC) study, a prospective cohort study conducted from 1991 to 2007 and comprising 172,000 participants, was utilized for this work. Women who were enrolled in NOWAC between 2006 and 2010 and had a diagnostic biopsy of breast cancer were requested to provide a second biopsy for research purposes. Furthermore, normal breast tissue was collected from NOWAC participants who were undergoing the national mammographic screening program. The study ultimately consisted of 279 age-matched case-control pairs, with the paired matched design being maintained throughout all laboratory analyses. Differences in tissue gene expression were identified using the Bioconductor R-package limma, utilizing Illumina microarray technology. The intrinsic subtypes were classified in both tissues using the PAM50 gene expression test. Results The findings revealed that nearly all genes displayed significant differential expression between cases and controls, with 10,013 out of 11,308 genes exhibiting statistical significance at an FDR q-value below 0.05. Among these, 5768 genes were upregulated while 4245 genes were downregulated. However, when parity (classified as 0, 1–3, 4–8 children) was incorporated into the model, only three genes in breast cancer tissue exhibited significant changes, while none were observed in normal tissue. Gene set enrichment analyses were non-informative. Furthermore, classification using PAM50 failed to establish any relationship between parity and the different intrinsic subtypes in either tissue. Conclusions Our study revealed no significant differences in gene expression between normal and breast cancer tissue in relation to the number of full-term pregnancies or parity.