Genetic Insights Into Hypertension and Breast Cancer Risk in African Women: A Mendelian Randomization and...

Area of Science:

• Genetics
• Epidemiology
• Public Health

Background:

• Breast cancer (BC) is a significant global health issue.
• Observational studies suggest a link between hypertension and BC risk, but causality is unproven.

Purpose of the Study:

• To investigate the causal effect of genetically predicted hypertension on overall BC risk and its molecular subtypes using Mendelian randomization (MR).
• To explore potential shared genetic determinants between hypertension and BC in a sub-Saharan African population.

Main Methods:

• A univariate two-sample MR analysis was conducted using summary-level genetic data for hypertension from the AWI-Gen study (n=10,775).
• Multiple MR methods (IVW, MR-Egger, weighted median, etc.) and sensitivity analyses were employed.
• Colocalization and reverse MR analyses were performed to assess shared causal signals and reverse causality.

Main Results:

• No statistically significant associations were found between genetically predicted hypertension and overall BC or its molecular subtypes after Bonferroni correction.
• A nominal association for estrogen receptor-negative BC did not withstand multiple testing correction.
• Colocalization analyses indicated low probabilities of shared causal variants across BC subtypes.

Conclusions:

• This MR and colocalization study in a sub-Saharan African population found no evidence of a direct genetic causal relationship between hypertension and BC risk.
• Reported associations between hypertension and BC may be attributed to non-genetic metabolic or vascular mechanisms.
• Further research in diverse populations is needed to confirm findings and elucidate biological pathways.