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

  • سال انتشار: 1400
  • محل انتشار: فصلنامه آسیب شناسی ایران، دوره: 16، شماره: 1
  • کد COI اختصاصی: JR_IJP-16-1_008
  • زبان مقاله: انگلیسی
  • تعداد مشاهده: 467
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نویسندگان

Zohreh Rahimi

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

Maryam Bozorgi Zarini Bozorgi Zarini

Department of Clinical Biochemistry, Kermanshah University of Medical Sciences

Ziba Rahimi

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

Ebrahim Shakiba

Department of Clinical Biochemistry, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran

Asad Vaisi-Raygani

Fertility and Infertility Research Center, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran

Mohammad Taher Moradi

Medical Biology Research Center, Kermanshah University of Medical Sciences

Kheirolah Yari

Medical Biology Research Center, Kermanshah University of Medical Sciences

چکیده

Background & Objective: Breast cancer (BC) is known to be the most prevalent cancer among women. One-carbon metabolism (OCM) 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 consisted of 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 tends to increase the BC metastasis.

کلیدواژه ها

Breast cancer, Thymidylate synthase, Methionine synthase, Methionine synthase reductase, Polymorphism, Metastasis

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