Influence of the CYP19A1 rs10046 Variant on Hormonal Signatures in Breast Cancer: Evidence from an Iraqi Cohort

Abstract

Breast cancer is the leading cause of diagnosed cancer cases in Iraq, making it the leading cause of cancer-related death among Iraqi women. BCs are characterized by genetic heterogeneity and complexity because of the overlap of numerous genes. Therefore, it is important to study genetic variants that increase the risk of breast cancer. Polymorphisms in genes encoding regulatory hormones have been shown to increase the risk of breast cancer. In addition, the level of estrogen is associated with the expression of the aromatase enzyme-encoding gene CYP19A1, which is a risk factor for breast cancer development. This study included 40 women with breast cancer and 40 women as controls. BC patient samples were collected from Baghdad Medical City Hospital and Baghdad-Iraq, and control samples were collected after confirming that the patients were free of any disease. Estradiol E2, progesterone, and testosterone T levels were measured using electrochemical chemiluminescence (ECL) with an automated Cobas e411 analyzer. DNA was extracted, and the CYP19A1 rs10046 gene was subjected to a PCR-RFLP technique. The results of the current study revealed p values for comparisons between women with breast cancer and control women, with estrogen, progesterone, and testosterone levels being 0.291, 0.18, and 0.473, respectively. Additionally, the E2/T ratio in the two study groups was 0.866. A positive correlation was also found between E2 and progesterone (p=0.46 P<0.001) and between progesterone and T (p=0.25 P<0.01). The distribution of the CYP19A1 rs10046 polymorphism in the patient population was 52.5% TT, 25% TC, and 22.5% CC, whereas in the control population, 52.5% TT, 32.5% TC, and 15% CC were present, and the allelic frequency was T=0.65 and C=0.35. Estradiol was significantly associated with the TC genotype. Breast cancer is an age-related disease that is strongly associated with menopause (p=0.80, P<0.001). These findings suggest that malignant tumors require age-related changes in the tissue or cellular microenvironment of the tumor, leading to the selection of mutations that promote the proliferation and spread of transformed cells. Elevated E2 levels may be positively correlated with the prognosis of patients with breast cancer. The discrepancy in hormone levels between the two groups may be attributed to the exclusion of menstrual cycle data from the study sample. E2 levels were associated with genotypes TT, TC and CC, particularly TC. Therefore, the rs10046 polymorphism in the Iraqi population may have a predictive and diagnostic role. These findings contribute to understanding the genetic basis of breast cancer.