# All-Cause Mortality and Cancer Risk Dependent on Blood Se Level and HRG rs10770 Genotypes on a Prospective Cohort of Women with Familial Breast Cancers

## TL;DR

This study found that blood selenium levels and HRG genotypes influence mortality and cancer risk in women with a family history of breast cancer.

## Contribution

The study reveals that HRG genotypes modify the effect of selenium on mortality and cancer risk in a high-risk cohort.

## Key findings

- Low selenium levels in Q1 were linked to higher mortality risk compared to Q4, regardless of HRG genotype.
- Women with HRG non-TT genotype and low selenium had a 7.68-fold higher mortality risk compared to higher quartiles.
- HRG TT genotype carriers under 50 had increased cancer risk in Q1 compared to Q2.

## Abstract

The aim of this study was to investigate whether genotypes of HRG may modify the effect of Se(selenium) on all-cause mortality and cancer risk. The study was conducted on 2782 initially unaffected women from families with familial breast cancers, all registered at the Hereditary Cancer Centre in Szczecin. Participants were aged 40 years or older and were recruited between September 2010 and March 2024. Women carrying a BRCA1 mutation and those with a diagnosed cancer were excluded from the study. Blood Se levels were measured using inductively coupled plasma mass spectrometry, and molecular analyses of HRG (Histidine-rich glycoprotein) genotypes were performed using real-time PCR with TaqMan probes. After an average follow-up period of 6 years and 2 months, 89 deaths and 210 cases of cancer were identified. The study showed significant differences in the reference range of blood selenium levels, as well as its impact on all-cause mortality and cancer risk, depending on HRG genotype. The most striking finding regarding all-cause mortality risk was observed among women over 50 years of age, effect estimates are presented as hazard ratios (HRs) with 95% confidence intervals (CIs). Regardless of genotype, women with blood selenium (Se) levels in the lowest quartile (Q1) had a significantly higher all-cause mortality risk compared with those in the highest quartile (Q4), (HR = 3.07; 95%CI: 1.53–6.16; p = 0.001). Among women with the HRG non-TT genotype, the risk was even more pronounced—those with Se levels in Q1 had a significantly increased mortality risk compared with women in the higher quartiles (Q2–Q4) (HR = 7.68; 95%CI: 2.31–25.47; p = 0.0008). In contrast, for carriers of the HRG TT genotype, increased all-cause mortality risk was observed only when blood Se levels were in Q1 compared with Q4 (HR = 2.40; 95%CI: 1.09–5.31; p = 0.029). Important findings for any cancer risk have emerged in women below 50 years of age. Among women with the HRG TT genotype, the cancer risk was significantly increased in Q1 compared with women in Q2 (HR = 4.15; 95%CI: 1.55–11.06; p = 0.004). In contrast, the results for HRG non-TT carriers, regardless of genotype, were statistically insignificant. In summary, mortality and cancer risk appeared to be dependent on HRG genotype and blood Se levels.