نوع مقاله : مقاله پژوهشی

نویسندگان

1 دانشگاه تبریز

2 عضو هیات علمی/ دانشگاه تبریز

3 دانشگاه شهید مدنی آذربایجان

چکیده

زمینه و هدف: سرطان سینه یکی از علل اصلی مرگ و میر در میان زنان ایرانی است. پروتئین RAD51 انسانی، نقشی مرکزی در ترمیم نوترکیبی همولوگ شکست‌های دو رشته‌ای DNA ایفا می‌کند و برای حفظ ثبات ژنوم ضروری است. اخیراً نشان داده شده است که یک چندشکلی تک نوکلئوتید (SNP) در منطقه ′5 غیر کدشونده‌ی ژن RAD51 (RAD51 135G˃C) خطر ابتلا به سرطان سینه را تغییر می‌دهد. هدف مطالعه حاضر، یافتن رابطه‌ی SNP مذکور با خطر ابتلا به سرطان سینه در میان زنان ترکی-آذری ایرانی است.
مواد و روش‌ها: این مطالعه بر روی 127 بیمار مبتلا به سرطان سینه و 125 نمونه‌ی شاهد انجام شد. DNA ژنومی با استفاده از روش استاندارد استخراج و چندشکلی RAD51 135G>C با استفاده از روش PCR مبتنی بر چند شکلی طولی قطعات برشی، مشخص گردید. ژنوتیپ‌ها با انجام توالی یابی تایید شدند و نهایتاً نتایج مورد بررسی آماری قرار گرفتند.
یافته‌ها: فراوانی ژنوتیپ‌های CC، CG و GGچندشکلی G>C 135 ژن RAD51 در گروه شاهد به ترتیب 1.61%، 20.16٪ و 78.22٪ و در افراد بیمار به ترتیب 2.36٪، 24.40٪ و 73.22٪ بودند. بررسی آماری نتایج نشان داد که بین گروه‌های بیمار و شاهد تفاوت معنی داری وجود ندارد.
نتیجه گیری: نتایج مطالعه حاضر حاکی از آن بود که بین چندشکلی G>C 135 ژن RAD51 با خطر ابتلا به سرطان سینه در جمعیت آذری ایرانی همراهی وجود ندارد.

کلیدواژه‌ها

موضوعات

عنوان مقاله [English]

RAD51 135G>C polymorphism and breast cancer risk in Northwest of Iran

نویسندگان [English]

  • Sonia Faridi 1
  • Narges Zeinal zadeh 2

چکیده [English]

Background and objective: Breast cancer is one of the main causes of death among Iranian women. Human RAD51 protein, play a central role in homologous recombination repair of double-stranded DNA breaks and is essential for maintaining genomic stability. A single nucleotide polymorphism in the 5′-untranslated region of RAD51 gene (RAD51 135G˃C) is reported to modulate breast cancer risk. The aim of this study was to find out the relationship of this SNP with breast cancer risk among Iranian Azeri Turkish women.
Materials and methods: This case-control study was performed on 127 breast cancer cases and 125 controls. Genomic DNA was extracted and the RAD51 135G > C genotype was determined using a PCR–Restriction Fragment Length Polymorphism (RFLP) based assay and confirmed by sequencing. The results were analyzed statistically.
Results: The frequencies of CC, CG and GG genotypes of RAD51 135G˃C were 1.613%, 20.161% and 78.225% in control group and 2.362%, 24.409% and 73.228% in patients, respectively. The results showed no significant differences among patients and controls groups.
Conclusion: The data presented here may suggest that the RAD51 135G > C polymorphism is not associated with breast cancer risk in Iranian Azeri population.

کلیدواژه‌ها [English]

  • Breast Cancer
  • RAD51 135G > C polymorphism
  • Azeri-Turkish
  • Iran
[1].    Ghoncheh M, Mohammadian-Hafshejani A, Salehiniya H. Incidence and mortality of breast cancer and their relationship to development in Asia. Asian Pac J Cancer Prev. 2015 Dec; 16(14): 6081-7.
[2].   Kim Y, Yoo KY, Goodman MT. Differences in Incidence, Mortality and Survival of Breast Cancer by Regions and Countries in Asia and Contributing Factors. Asian Pac J Cancer Prev. 2015 Apr; 16(7): 2857-70.
[3].   Almasi Z, Mohammadian-Hafshejani A, Salehiniya H. Incidence, mortality, and epidemiological aspects of cancers in Iran; differences with the world data. Journal of BU ON.: Official Journal of the Balkan Union of Oncology. 2016 Jul 1; 21(4): 994-1004.
[4].   Mousavi SM, Montazeri A, Mohagheghi MA, Jarrahi AM, Harirchi I, Najafi M, Ebrahimi M. Breast cancer in Iran: an epidemiological review. The Breast Journal. 2007 Jul 1; 13(4): 383-91.
[5].   Rudolph A, Chang-Claude J, Schmidt MK. Gene–environment interaction and risk of breast cancer. British Journal of Cancer. 2016 Jan 19; 114(2): 125-33.
[6].   BRCA SG. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science. 1994 Oct; 266: 7.
[7].   Wooster R, Bignell G, Lancaster J, Swift S. Identification of the breast cancer susceptibility gene BRCA2. Nature. 1995 Dec 21; 378(6559): 789.
[8].   Malkin D, Li FP, Strong LC, Nelson CE, Kim DH. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science. 1990 Nov 30; 250(4985): 1233.
[9].   Hirotsu Y, Nakagomi H, Sakamoto I, Amemiya K, Oyama T, Mochizuki H, Omata M. Multigene panel analysis identified germline mutations of DNA repair genes in breast and ovarian cancer. Molecular Genetics & Genomic Medicine. 2015 Sep 1; 3(5): 459-66.
[10].Tung N, Lin NU, Kidd J, Allen BA, Singh N, Wenstrup RJ, Hartman AR, Winer EP, Garber JE. Frequency of germline mutations in 25 cancer susceptibility genes in a sequential series of patients with breast cancer. Journal of Clinical Oncology. 2016 Mar 14; 34(13): 1460-8.
[11].Michailidou K, Hall P, Gonzalez-Neira A, Ghoussaini M, Dennis J, Milne RL, Schmidt MK, Chang-Claude J, Bojesen SE, Bolla MK, Wang Q. Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nature Genetics. 2013 Apr 1; 45(4): 353-61.
[12].Holthausen JT, Wyman C, Kanaar R. Regulation of DNA strand exchange in homologous recombination. DNA Repair. 2010 Dec 10; 9(12): 1264-72.
[13].Benson FE, Stasiak A, West SC. Purification and characterization of the human Rad51 protein, an analogue of E. coli RecA. The EMBO Journal. 1994 Dec 1; 13(23): 5764.
[14].Walsh T, King MC. Ten genes for inherited breast cancer. Cancer Cell. 2007 Feb 13; 11(2): 103-5.
[15].Hu J, Wang N, Wang YJ. XRCC3 and RAD51 expression are associated with clinical factors in breast cancer. PloS One. 2013 Aug 20; 8(8): e72104.
[16].Khanna KK, Jackson SP. DNA double-strand breaks: signaling, repair and the cancer connection. Nature Genetics. 2001 Mar 1; 27(3): 247-54.
[17].Wasson MK, Chauhan PS, Singh LC, Katara D, Sharma JD, Zomawia E, Kataki A, Kapur S, Saxena S. Association of DNA repair and cell cycle gene variations with breast cancer risk in Northeast Indian population: a multiple interaction analysis. Tumor Biology. 2014 Jun 1; 35(6): 5885.
[18].Tulbah S, Alabdulkarim H, Alanazi M, Parine NR, Shaik J, Pathan AA, Al-Amri A, Khan W, Warsy A. Polymorphisms in RAD51 and their relation with breast cancer in Saudi females. OncoTargets and Therapy. 2016; 9: 269.
[19].Hosseini M, Houshmand M, Ebrahimi A. RAD51 polymorphisms and breast cancer risk. Molecular Biology Reports. 2013 Jan; 1: 1-4.
[20].Howe JR, Klimstra DS, Cordon-Cardo C. DNA extraction from paraffin-embedded tissues using a salting-out procedure: a reliable method for PCR amplification of archival material. Histology and Histopathology. 1997 Jul; 12(3): 595-601.
[21].Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Research. 1988 Feb 11; 16(3): 1215.
[22].Smith TR, Levine EA, Freimanis RI, Akman SA, Allen GO, Hoang KN, Liu-Mares W, Hu JJ. Polygenic model of DNA repair genetic polymorphisms in human breast cancer risk. Carcinogenesis. 2008 Aug 13; 29(11): 2132-8.
[23].Shi S, Qin L, Tian M, Xie M, Li X, Qi C, Yi X. The effect of RAD51 135 G> C and XRCC2 G> A (rs3218536) polymorphisms on ovarian cancer risk among Caucasians: a meta-analysis. Tumor Biology. 2014 Jun 1; 35(6): 5797.
[24].Cheng D, Shi H, Zhang K, Yi L, Zhen G. RAD 51 Gene 135G/C polymorphism and the risk of four types of common cancers: a meta-analysis. Diagnostic Pathology. 2014 Jan 23; 9(1): 18.
[25].Sekhar D, Pooja S, Kumar S, Rajender S. RAD51 135G> C substitution increases breast cancer risk in an ethnic-specific manner: a meta-analysis on 21236 cases and 19407 controls. Scientific Reports. 2015 Jun 25; 5: srep11588.
[26].Aleskandarany M, Caracappa D, Nolan CC, Macmillan RD, Ellis IO, Rakha EA, Green AR. DNA damage response markers are differentially expressed in BRCA-mutated breast cancers. Breast Cancer Research and Treatment. 2015; 150(1): 81.
[27].Klopfleisch R, Schütze M, Gruber AD. RAD51 protein expression is increased in canine mammary carcinomas. Veterinary Pathology. 2010 Jan; 47(1): 98-101.
[28].Nowacka-Zawisza M, Bryś M, Romanowicz-Makowska H, Kulig A, Krajewska WM. Loss of heterozygosity in the RAD51 and BRCA2 regions in breast cancer. Cancer Detection and Prevention. 2008 Dec 31; 32(2): 144-8.
[29].Hasselbach L, Haase S, Fischer D, Kolberg HC, Sturzbecher HW. Characterisation of the promoter region of the human DNA-repair gene Rad51. Eur J Gynaecol Oncol. 2005 Feb; 26: 589-598.
[30].Thacker J. The RAD51 gene family, genetic instability and cancer. Cancer Lett. 2005 Mar; 219: 125-135.
[31].Wang WW, Spurdle AB, Kolachana P, Bove B, Modan B, Ebbers SM, Suthers G, Tucker MA, Kaufman DJ, Doody MM, Tarone RE. A single nucleotide polymorphism in the 5′ untranslated region of RAD51 and risk of cancer among BRCA1/2 mutation carriers. Cancer Epidemiology and Prevention Biomarkers. 2001 Sep 1; 10(9): 955-60.
[32].Krupa R, Synowiec E, Pawlowska E, Morawiec Z, Sobczuk A, Zadrozny M, Wozniak K, Blasiak J. Polymorphism of the homologous recombination repair genes RAD51 and XRCC3 in breast cancer. Experimental and Molecular Pathology. 2009 Aug 31; 87(1): 32-5.
.