The Role of HMGA1 and Height in Breast Cancer Risk and Prognosis: Insights from UK Biobank Data

Background/Aim: Tall women are more likely to develop breast cancer (BC). High Mobility Group AT-Hook 1 (HMGA1), an oncofetal protein, plays a role in BC progression. Variants near HMGA1 have been associated with increased height. This study examines the relationship between HMGA1, height, and BC risk and prognosis using UK Biobank data. Patients and Methods: Data from 10,527 women with invasive BC were analyzed. Subjects were grouped by height: short (<155 cm), medium (155-175 cm), and tall (>175 cm). HMGA1 SNP rs41269028, a single nucleotide intron variant, was evaluated for its influence on height, BC risk, and survival. Statistical analysis included Fisher’s exact test, regression models, and survival analysis using the log-rank test. Results: HMGA1 SNP rs41269028 carriers (CT+TT) were taller (162.88 cm) compared to homozygotes for the major allele (162.29 cm, p=0.005). Tall women with BC showed poorer survival than short women (p=0.032). However, HMGA1 genotype did not significantly affect BC risk (p=0.602) or survival (p=0.439). Multivariate analysis confirmed an independent effect of age and HMGA1 genotype on height. Conclusion: While HMGA1 influences height, no direct association with increased BC risk or poor prognosis in tall women was demonstrated. Nevertheless, tall women with BC had worse survival, suggesting height might be considered in treatment decisions. Future studies should explore mechanisms linking height to BC outcomes.