Article Data

  • Views 418
  • Dowloads 127

Original Research

Open Access

The association between polymorphisms of the RAD51-G135C, XRCC2-Arg188His and XRCC3-Thr241Met genes and clinico-pathologic features in breast cancer in Poland

  • H. Romanowicz-Makowska1,*,
  • B. Smolarz1
  • M. Zadrożny2
  • B. Westfal2
  • J. Baszczyński2
  • G. Kokołaszwili3
  • M. Burzyński3
  • I. Połać4
  • S. Sporny5

1Laboratory of Molecular Genetics, Department of Pathology, Institute of Polish Mother’s Memorial Hospital, Lodz, Poland

2Department of Oncology, Institute of Polish Mother’s Memorial Hospital, Lodz, Poland

3Department of Obstetrics and Gynecology, Regional Hospital in Lowicz, Poland

4Department of Menopausal Diseases, Institute of Polish Mother’s Memorial Hospital, Lodz, Poland

5Department of Pathology, Medical University of Lodz, Poland

DOI: 10.12892/ejgo201202145 Vol.33,Issue 2,March 2012 pp.145-150

Published: 10 March 2012

*Corresponding Author(s): H. Romanowicz-Makowska E-mail: smolbea@wp.pl

Abstract

Background: XRCC2 and XRCC3 genes are structurally and functionally related to RAD51 which plays an important role in homologous recombination, the process frequently involved in cancer transformation. Material and Methods: In the present work the distribution of genotypes and frequency of alleles of the RAD51 G135C polymorphism, XRCC2 Arg188His and XRCC3 Thr241Met polymorphism in 790 cases of breast cancer were investigated. The control group consisted of 798 cancer-free blood donors (age 5 years) who were sex and ethnicity-matched. The polymorphisms were determined by PCR-RFLP methods. We also correlated genotypes with the clinical characteristics of breast cancer patients. Results: Our results obtained for the 135G>C polymorphism of the RAD51 gene indicated that both the C/C genotype and the C allele are strongly associated with breast cancer. The Arg/His genotype of XRCC2 (OR = 2.16, 95% CI = 1.48-3.16) and Thr/Met of XRCC3 increased the risk of type 1 breast cancer occurrence (OR = 2.33,95% CI = 1.60-3.41). We did not find any association with the RAD51. XRCC2/3 gene polymorphism and estrogen and progesterone receptor status. Conclusion: The results support the hypothesis that the polymorphism of RAD51 and XRCC2/3 gene may be associated with the incidence of sporadic breast cancer in Polish women.

Keywords

RAD51; XRCC2; XRCC3; Breast cancer; Gene polymorphism

Cite and Share

H. Romanowicz-Makowska,B. Smolarz,M. Zadrożny,B. Westfal,J. Baszczyński,G. Kokołaszwili,M. Burzyński,I. Połać,S. Sporny. The association between polymorphisms of the RAD51-G135C, XRCC2-Arg188His and XRCC3-Thr241Met genes and clinico-pathologic features in breast cancer in Poland. European Journal of Gynaecological Oncology. 2012. 33(2);145-150.

References

[1] Davidson J.M., Gorringe K.L., Chin S.F., Orsetti B., Besret C., Courtay-Cahen C. et al.: “Molecular cytogenetic analysis of breast cancer cell lines”. Br. J. Cancer, 2000, 83, 1309.

[2] Loveday R.L., Greenman J., Simcox D.L., Speirs V., Drew P.J., Monson J.R., Kerin M.J.: “Genetic changes in breast cancer detected by comparative genomic hybridisation”. Int. J. Cancer, 2000, 86, 494.

[3] Khanna K.K., Jackson S.P.: “DNA double-strand breaks: signaling, repair and the cancer connection”. Nat. Genet., 2001, 27, 247.

[4] Bahar R., Hartmann C.H., Rodriguez K.A., Denny A.D., Busuttil R.A., Dolle M.E. et al.: “Increased cell-to-cell variation in gene expression in ageing mouse heart”. Nature, 2006, 441, 1011.

[5] Vijg J., Dolle M.E.T.: “Large genome rearrangements as a primary cause of aging”. Mech. Ageing Dev., 2002, 123, 907.

[6] Jackson S.P.: “Sensing and repairing DNA double-strand breaks”. Carcinogenesis, 2002, 23, 687.

[7] Helleday T.: “Pathways for mitotic homologous recombination in mammalian cells”. Mutat. Res., 2003, 532, 103.

[8] Lieber M.R., Ma Y., Pannicke U., Schwarz K.: “Mechanisms and regulation of human non-homologous DNA end-joining”. Mol. Cell. Biol., 2003, 4, 712.

[9] Karagiannis A. El-Osta: “Double-strand breaks: signalling pathways and repair mechanisms”. Cell. Mol. Life Sci., 2004, 61, 2137.

[10] Benhamou S., Tuimala J., Bouchardy C., Dayer P., Sarasin A., Hirvonen A.: “DNA repair gene XRCC2 and XRCC3 polymorphisms and susceptibility to cancers of the upper aerodigestive tract”. Int. J. Cancer, 2004, 112, 901.

[11] Jacobsen N.R., Nexo B.A., Olsen A., Overvad K., Wallin H., Tjonneland A., Vogel U.: “No association between the DNA repair gene XRCC3 T241M polymorphism and risk of skin cancer and breast cancer”. Cancer Epidemiol. Biomark. Prev., 2003, 12, 584.

[12] Webb P.M., Hopper J.L., Newman B., Chen X., Kelemen L., Giles G.G. et al.: “Double-strand break repair gene polymorphisms and risk of breast or ovarian cancer”. Cancer Epidemiol. Biomark Prev., 2005, 14, 319.

[13] Huang W.Y., Olshan A.F., Schwartz S.M., Berndt S.I., Chen C., Llaca V. et al.: “Selected genetic polymorphisms in MGMT, XRCC1, XPD, and XRCC3 and risk of head and neck cancer: a pooled analysis”. Cancer Epidemiol. Biomark Prev., 2005, 14, 1747.

[14] Matullo G., Guarrera S., Sacerdote C., Polidoro S., Davico L., Gamberini S. et al.: “Polymorphisms/haplotypes in DNA repair genes and smoking: a bladder cancer case-control study”. Cancer Epidemiol. Biomark Prev., 2005, 14, 2569.

[15] Garcia-Closas M., Egan K.M., Newcomb P.A., Brinton L.A., Titus-Ernstoff L., Chanock S. et al.: “Polymorphisms in DNA double-strand break repair genes and risk of breast cancer: two population-based studies in USA and Poland, and metaanalyses”. Hum. Genet., 2006, 119, 376.

[16] Zienolddiny S., Campa D., Lind H., Ryberg D., Skaug V., Stangeland L.: “Polymorphisms of DNA repair genes and risk of nonsmall cell lung cancer”. Carcinogenesis, 2006, 27, 560.

[17] Hasselbach S., Haase D., Fischer H.C., Kolberg, Stürzbecher H.W.: “Characterisation of the promoter region of the human DNA-repair gene RAD51”. Eur. J. Gynaecol. Oncol., 2005, 26, 589.

[18] Sliwinski T., Krupa R., Majsterek I., Rykala J., Kolacinska A., Morawiec Z. et al.: “Polymorphisms of the BRCA2 and RAD51 genes in breast cancer”. Breast Cancer Res. Treat., 2005, 94, 105.

[19] Blasiak J., Przybylowska K., Czechowska A., Zadrozny M., Pertynski T., Rykala J. et al.: “Analysis of the G/C polymorphism in the 5 -untranslated region of the RAD51 gene in breast cancer”. Acta Biochim. Pol., 2003, 50, 249.

[20] Levy-Lahad E., Lahad A., Eisenberg S., Dagan E., Paperna T., Kasinetz L. et al.: “A single nucleotide polymorphism in the RAD51 gene modifies cancer risk in BRCA2 but not BRCA1 carriers”. Proc. Natl. Acad. Sci. USA, 2001, 98, 3232.

[21] Wang W.W., Spurdle A.B., Kolachana P., Bove B., Modan B., Ebbers S.M. et al.: “A single nucleotide polymorphism in the 5’ untranslated region of RAD51 and risk of cancer among BRCA1/2 mutation carriers”. Cancer Epidemiol. Biomark. Prev., 2001, 10, 955.

[22] Kuschel B., Auranen A., McBride S., Novik K.L., Antoniou A., Lipscombe J.M. et al.: “Variants in DNA double-strand break repair genes and breast cancer susceptibility”. Hum. Mol. Genet., 2002, 11, 1399.

[23] Matullo G., Guarrera S., Sacerdote C., Polidoro S., Davico L., Gamberini S. et al.: “Polymorphisms/haplotypes in DNA repair genes and smoking: A bladder cancer case-control study”. Cancer Epidemiol. Biomarkers Prev., 2005, 14, 2569.

[24] Tranah G.J., Giovannucci E., Ma J., Fuchs C., Hankinson S.E., Hunter D.J.: “XRCC2 and XRCC3 polymorphisms are not associated with risk of colorectal adenoma”. Cancer Epidemiol. Biomarkers Prev., 2004, 13, 1090.

[25] Han J., Colditz G.A., Samson L.D., Hunter D.J.: “Polymorphisms in DNA double-strand break repair genes and skin cancer risk”. Cancer Res., 2004, 64, 3009.

[26] Han J., Hankinson S.E., Hunter D.J., De Vivo I.: “Genetic variations in XRCC2 and XRCC3 are not associated with endometrial cancer risk”. Cancer Epidemiol. Biomarkers Prev., 2004, 13, 330.

[27] Economopoulos K.P., Sergentanis T.N.: “XRCC3 Thr241Met polymorphism and breast cancer risk: a meta-analysis”. Breast Cancer Res. Treat., 2010, 121, 439.

[28] Jiang Z., Li C., Xu Y., Cai S.: “A meta-analysis on XRCC1 and XRCC3 polymorphisms and colorectal cancer risk”. Int. J. Colorectal Dis., 2010, 25, 169.

[29] Sun H., Qiao Y., Zhang X., Xu L., Jia X., Sun D. et al.: “XRCC3 Thr241Met polymorphism with lung cancer and bladder cancer: a meta-analysis”. Cancer Sci., 2010, 101, 1777.

[30] Sliwinski T., Walczak A., Przybylowska K., Rusin P., Pietruszewska W., Zielinska-Blizniewska H. et al.: “Polymorphisms of the XRCC3 C722T and the RAD51 G135C genes and the risk of head and neck cancer in a Polish population”. Exp. Mol. Pathol., 2010, 89, 358.

[31] Sannino P., Shousha S.: “Demonstration of estrogen receptors in paraffin wax sections of breast carcinoma using the monoclonal antibody 1D5 and microwave oven processing”. J. Clin. Pathol., 1994, 47, 90.

[32] Blasiak J., Przybylowska K., Czechowska A., Zadrozny M., Pertynski T., Rykala J. et al.: “Analysis of the G/C polymorphism in the 5’-untranslated region of the RAD51 gene in breast cancer”. Acta Biochim. Pol., 2003, 50, 249.

[33] Sliwinski T., Krupa R., Majsterek I., Rykala J., Kolacinska A., Morawiec Z. et al.: “Polymorphisms of the BRCA2 and RAD51 genes in breast cancer”. Breast Cancer Res. Treat., 2005, 94, 105.

[34] Krupa R., Synowiec E., Pawlowska E., Morawiec Z., Sobczuk A., Zadrozny M. et al.: “Polymorphism of the homologous recombination repair genes RAD51 and XRCC3 in breast cancer”. Exp. Mol. Pathol., 2009, 87, 32.

[35] Jara L., Dubois K., Gaete D., de Mayo T., Ratkevicius N., Bravo T., Margarit S. et al.: “Variants in DNA double-strand break repair genes and risk of familial breast cancer in a South American population”. Breast Cancer Res. Treat., 2010, 122, 813.

[36] Gao L.B., Pan X.M., Li L.J., Liang W.B., Zhu Y., Zhang L.S. et al.: “RAD51 135G/C polymorphism and breast cancer risk: a meta-analysis from 21 studies”. Breast Cancer Res. Treat., 2011, 125, 827.

[37] Wang Z., Dong H., Fu Y., Ding H.: “RAD51 135G>C polymorphism contributes to breast cancer susceptibility: a meta-analysis involving 26,444 subjects”. Breast Cancer Res. Treat., 2010, 124, 765.

[38] Synowiec E., Stefanska J., Morawiec Z., Blasiak J., Wozniak K.: “Association between DNA damage, DNA repair genes variability and clinical characteristics in breast cancer patients”. Mutat. Res., 2008, 648, 65.

[39] Romanowicz H., Smolarz B., Baszczyn´ski J., Zadroz·ny M., Kulig A.: “Genetics polymorphism in DNA repair genes by base excision repair pathway (XRCC1) and homologous recombination (XRCC2 and RAD51) and the risk of breast carcinoma in the Polish population”. Pol. J. Pathol., 2010, 61, 206.

[40] Loizidou M.A., Michael T., Neuhausen S.L., Newbold R.F., Marcou Y., Kakouri E. et al.: “Genetic polymorphisms in the DNA repair genes XRCC1, XRCC2 and XRCC3 and risk of breast cancer in Cyprus”. Breast Cancer Res. Treat., 2008, 112, 575.

[41] Krupa R., Synowiec E., Pawlowska E., Morawiec Z., Sobczuk A., Zadrozny M. et al.: “Polymorphism of the homologous recombination repair genes RAD51 and XRCC3 in breast cancer”. Exp. Mol. Pathol., 2009, 87, 32.

[42] Sobczuk A., Romanowicz-Makowska H., Fiks T., Baszczyn´ski J., Smolarz B.: “XRCC1 and XRCC3 DNA repair gene polymorphisms in breast cancer women from the Lodz region of Poland”. Pol. J. Pathol., 2009, 60, 76.

[43] Economopoulos K.P., Sergentanis T.N.: “XRCC3 Thr241Met polymorphism and breast cancer risk: a meta-analysis”. Breast Cancer Res. Treat., 2010, 121, 439.

[44] Rafii S., O’Regan P., Xinarianos G., Azmy I., Stephenson T., Reed M. et al.: “A potential role for the XRCC2 R188H polymorphic site inDNA-damage repair and breast cancer”. Hum. Mol. Genet., 2002, 11, 1433.

[45] Yu K.D., Chen A.X., Qiu L.X., Fan L., Yang C., Shao Z.M.: “XRCC2 Arg188His polymorphism is not directly associated with breast cancer risk: evidence from 37,369 subjects”. Breast Cancer Res. Treat., 2010, 123, 219.

Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.

Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.

JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.

Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.

BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Submission Turnaround Time

Conferences

Top