Page 112 - EJMO-9-1

Eurasian Journal of Medicine and
Oncology
Genomics of breast cancer in Western Kazakhstan

the codominant model for the T/C genotype (OR = 53.58, Regarding the AR gene polymorphism, no studies were
95% CI: 22.72 – 126.32, P = 0); in the dominant model for found in the available literature linking it to BC.
the T/C-T/T genotypes (OR = 39.56, 95% CI: 18.61 – 84.1, In univariate analysis for BC risk prediction, 32
P = 0); and in the overdominant model for the T/C genotype statistically significant factors were identified, with risk
(OR = 24.41, 95% CI: 12.3 – 48.46, P = 0). However, no studies levels ranging from 69.7% to 90.6%. Among these, the most
in the available literature have investigated the association of important factors were Rs137852985 (TC, TT), Rs2229774
RARG missense variants with BC development. It is known (AG, AA), and Rs2981582 (AG, AA). When constructing
that the first published GWAS catalog for anthracycline- the predictive model (decision tree), the primary high-
induced heart failure identified a significant missense
variant in RARG (Ser427Leu, TCG>TTG, and Rs2229774). risk classes for BC development, with a risk level of 95.8%,
15
A prospective cohort study further evaluated the potential were identified as age <54.0 years, Rs2229774 (AG),
for combined testing of RARG Rs2229774, SLC28A3 and Rs889312 (AA, CC). The predictive quality of the
Rs7853758, and UGT1A6*4 Rs17863783 polymorphisms to constructed model was found to be high.
predict doxorubicin-related cardiotoxicity in a large cohort 5. Conclusion
of patients with identical diagnoses. 16
Seven statistically significant risk polymorphisms
Our results revealed that the Rs889312 polymorphism
in the MAP3K1 gene (a common variation) increased the associated with the risk of developing BC have been
identified and are included in the GWAS catalog: RARG
risk of BC in the dominant inheritance model for the A/C- (Rs2229774), FGFR2 (Rs2981582), ATM (Rs1800057),
C/C genotypes (OR = 1.78, 95% CI: 1.04 – 3.06, P = 0.003)
and the recessive model for the C/C genotype (OR = 2.17, MAP3K1 (Rs889312), BRCA2 (Rs11571833), FGFR2
95% CI: 1.19 – 3.95). These findings are consistent with (Rs7895676), and FGFR2 (Rs1219648). A strong genotype-
Abbasi et al.’s study, which reported that the Rs889312 phenotype association has been found between five SNPs
17
polymorphism in the MAP3K1 gene is associated with BC in and the risk of developing BC across five genetic models:
Pakistani women. In that study, the OR was 0.55 (95% CI: 0.31 Rs2981582 of the FGFR2 gene, Rs2229774 of the RARG
– 0.96) for the wild-type AA homozygote, OR = 1.30 (95% gene, Rs889312 of the MAP3K1 gene, Rs137852985 of
CI: 0.74 – 2.26) for the heterozygote AC, and OR = 7.06 (95% the BRIP1 gene, and Rs137852576 of the AR gene. Thirty-
CI: 1.23 – 40.34) for the rare allele CC homozygote. two prognostic factors for the risk of developing BC have
been identified, with risk levels ranging from 69.7% to
The association between the Rs889312 polymorphism 90.6%. The most important factors are Rs137852985
and BC incidence has been well-documented in (BRIP1), Rs2229774 (RARG), and Rs2981582 (FGFR2).
populations from East Asia, North Africa, and the A predictive model for BC risk has been developed with
Northern Hemisphere. These studies, conducted in BC a high-quality score (0.88) and a risk assessment of 95%
patients, aimed to determine the likelihood of SNPs being when combining polymorphisms included in the GWAS
associated with disease development and/or progression. catalog: Rs2229774 (RARG), Rs889312 (MAP3K1), and
Strong associations were observed in the GWAS study the factor age <54.0 years.
conducted by Easton et al., which included 3,882 BC
18
patients from the European Network of Excellence for Acknowledgments
Cancer using population-based registries and biobank data
(CCPRB). A previous meta-analysis, designed to verify the None.
association of Rs889312 with BC risk, demonstrated that Funding
this polymorphism was associated with an increased risk of
BC in both small and large population models. Studies by This research was funded by the Ministry of Education and
19
Jara et al. also indicated an association between Rs889312 Science of the Republic of Kazakhstan as part of the project
20
and BC risk in Latin America. Furthermore, the MAP3K1 “New Molecular-Genetic Methods for Pre-Symptomatic
Rs889312 genotype was found to be associated with larger Diagnosis and Treatment of Several Significant Diseases”
breast tumors in Asians, but not in Europeans. 21 (State Registration Number 0117RK00036; Project Leader:
Meta-analysis data by Zheng et al. 19,p.8 showed that “the Ramazanova B.A., Asfendiyarov Kazakh National Medical
MAP3K1 gene polymorphism (Rs889312) is associated University), 2019.
with BC risk in Europeans and Asians (as in our study), Conflict of interest
whereas Rs16886165 is a risk factor for BC in Asian and
African women, and both may serve as markers of BC The authors declare that they have no competing
predisposition.” interests.

Volume 9 Issue 1 (2025) 104 doi: 10.36922/ejmo.5385