Gene Expression Profiling of Peripheral Blood and Endometrial Cancer Risk Factors: Systems Epidemiology Approach in...

Area of Science:

• Genomics
• Cancer Research
• Epidemiology

Background:

• Endometrial cancer (EC) incidence is rising, necessitating new preventive strategies.
• Understanding pre-diagnostic genetic changes is crucial for predictive modeling.
• Established EC risk factors include parity, menstruation, coffee, BMI, menopause age, and oral contraceptive use.

Purpose of the Study:

• To investigate if known endometrial cancer risk factors affect peripheral blood gene expression prospectively.
• To identify associations between EC risk factors and gene expression profiles in women.

Main Methods:

• Selected EC risk factors from a large prospective cohort (165,000 women).
• Employed BeadChip microarray technology in a nested case-control study (79 pairs) from the NOWAC postgenome cohort.
• Conducted gene set enrichment analysis (GSEA).

Main Results:

• No overall gene expression differences were found between EC cases and controls.
• Parity status changes were linked to 1,379 gene expressions in controls, but not in EC cases.
• BMI changes correlated with 27 gene expressions in controls, but not in EC cases.
• GSEA revealed 2407 significantly enriched gene sets associated with parity in cancer-free women.

Conclusions:

• Increased parity has a lifelong impact on peripheral blood gene expression in women who do not develop cancer.
• Neither multiparity nor elevated BMI altered gene expression in women later diagnosed with endometrial cancer.
• These findings highlight distinct gene expression patterns related to risk factors in cancer-free versus pre-cancerous individuals.