Germline APOE ε2 homozygosity and reduced risk of breast cancer: a population-based cohort study

초록

We evaluated whether Apolipoprotein E (APOE) epsilon 2 homozygosity, a germline variant associated with lower LDL cholesterol, is linked to reduced risk of breast cancer. We analyzed data from 234,857 cancer-free and dementia-free women in the UK Biobank. APOE genotypes were classified as epsilon 2 homozygotes, epsilon 2 heterozygotes, and non-epsilon 2 carriers. Incident breast cancer was assessed via national registry linkage. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs). Subgroup analyses were conducted by lifestyle, metabolic, and female-specific factors. Over a median follow-up of 12.3 years, 7,961 first primary breast cancers occurred. Compared to non-epsilon 2 carriers, epsilon 2 homozygotes had significantly lower breast cancer risk (HR, 0.64; 95% CI 0.45-0.90). The protective association of epsilon 2/epsilon 2 was stronger in participants with smoking history. APOE epsilon 2 homozygosity was associated with reduced risk of breast cancer, particularly under inflammatory stress. These findings suggest that genetically determined lipid and inflammatory regulation may influence breast cancer susceptibility.

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