Variants of Genes Involved in Metabolism of Folate Among Patients with Breast Cancer: Association of TYMS 3R Allele with Susceptibility to Breast Cancer and Metastasis.

Kheirolah Yari,Ziba Rahimi,Mohammad Taher Moradi,Maryam Bozorgi Zarini Bozorgi Zarini,Zohreh Rahimi,Ebrahim Shakiba,Asad Vaisi-Raygani

doi:10.30699/ijp.2020.117676.2283

Kheirolah Yari, Ziba Rahimi + Show 5 more

Open Access

https://doi.org/10.30699/ijp.2020.117676.2283

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Abstract

Background & Objective:Breast cancer (BC) is known to be the most prevalent cancer among women. One-carbon metabolism disturbance might play an important role in the etiology of BC. The present study aimed to investigate the thymidylate synthase (TYMS), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), and methionine synthase reductase (MTRR) variants as good candidates for studying the role of genetic variants of folate metabolizing enzymes in the risk of BC.Methods:The present case-control study includes 100 BC patients and 141 healthy females. The TYMS 2R/3R (rs34743033), MTR c.2756A>G (rs1805087), and MTRR c.66A>G (rs1801394) variants were detected by polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism (RFLP), and a designed amplification-refractory mutation system (ARMS) method, respectively.Results:The 3R allele of TYMS enhanced the risk of BC by 2.84-fold (P<0.001). In the presence of TYMS 3R/3R, compared to TYMS 2R/3R, there was a trend toward enhancing the risk of metastasis by 4.15-fold (95% CI: 0.96-17.85, P=0.055). The frequencies of MTR c.2756A>G and MTRR c.66A>G variants were not significantly different among patients and controls.Conclusion:We observed that the TYMS 3R is a risk allele for susceptibility to BC and this allele may increase the risk of metastasis in BC patients. .

Highlights

Background & ObjectiveBreast cancer (BC) is known to be the most prevalent cancer among women
Breast cancer (BC) is the most prevalent cancer among women accounting for 16% of all cancers in females [1]
Diagnosis of BC is critical for treatment of the disease and reducing the mortality rates [3]

Summary

Methods

The present case-control study includes 100 BC patients and 141 healthy females. The TYMS 2R/3R (rs34743033), MTR c.2756A>G (rs1805087), and MTRR c.66A>G (rs1801394) variants were detected by polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism (RFLP), and a designed amplification-refractory mutation system (ARMS) method, respectively. We studied 100 BC patients (99 females and 1 male) aged 49.5±10.2 years (29–79 years) and 141 healthy females aged 38.7±9.4 years (range 28–70 years). All patients had been admitted to a university hospital affiliated to the Kermanshah University of Medical Sciences (KUMS), Iran. The ethnic background of both patients and controls was Kurdish. The Ethics Committee of KUMS approved the study. All patients and healthy controls agreed to participate in the study and a written informed consent was obtained from all participants prior to conducting the study. The study was in accordance with the principles of the Helsinki II declaration

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Conclusion