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Published in: Breast Cancer Research and Treatment 3/2010

01-12-2010 | Epidemiology

RAD51 135G>C polymorphism contributes to breast cancer susceptibility: a meta-analysis involving 26,444 subjects

Authors: Zhanwei Wang, Hairong Dong, Yuanyuan Fu, Haixia Ding

Published in: Breast Cancer Research and Treatment | Issue 3/2010

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Abstract

RAD51 plays a key role in homologous recombination repair of double-stranded DNA breaks which may cause chromosomal breaks and genomic instability. We performed a meta-analysis of 9 epidemiological studies involving 13,241 cases and 13,203 controls that examined the association between RAD51 135G>C polymorphism and breast cancer. No significant association of RAD51 135G>C polymorphism with breast cancer was found in overall and European populations. However, after the studies which did not fulfill Hardy–Weinberg equilibrium were excluded, we observed an overall significant increased breast cancer risk (for the recessive model CC vs. GG/CG: OR = 1.35, 95% CI = 1.05–1.74, P heterogeneity = 0.06). In summary, our meta-analysis suggested the RAD51 135G>C polymorphism may contribute to breast cancer susceptibility.
Literature
1.
go back to reference Henning W, Sturzbecher HW (2003) Homologous recombination and cell cycle checkpoints: Rad51 in tumour progression and therapy resistance. Toxicology 193:91–109CrossRefPubMed Henning W, Sturzbecher HW (2003) Homologous recombination and cell cycle checkpoints: Rad51 in tumour progression and therapy resistance. Toxicology 193:91–109CrossRefPubMed
2.
go back to reference Tsuzuki T, Fujii Y, Sakumi K, Tominaga Y, Nakao K, Sekiguchi M, Matsushiro A, Yoshimura Y, Morita T (1996) Targeted disruption of the Rad51 gene leads to lethality in embryonic mice. Proc Natl Acad Sci USA 93:6236–6240CrossRefPubMed Tsuzuki T, Fujii Y, Sakumi K, Tominaga Y, Nakao K, Sekiguchi M, Matsushiro A, Yoshimura Y, Morita T (1996) Targeted disruption of the Rad51 gene leads to lethality in embryonic mice. Proc Natl Acad Sci USA 93:6236–6240CrossRefPubMed
3.
4.
5.
go back to reference Lose F, Lovelock P, Chenevix-Trench G, Mann GJ, Pupo GM, Spurdle AB (2006) Variation in the RAD51 gene and familial breast cancer. Breast Cancer Res 8:R26CrossRefPubMed Lose F, Lovelock P, Chenevix-Trench G, Mann GJ, Pupo GM, Spurdle AB (2006) Variation in the RAD51 gene and familial breast cancer. Breast Cancer Res 8:R26CrossRefPubMed
6.
go back to reference Levy-Lahad E, Lahad A, Eisenberg S, Dagan E, Paperna T, Kasinetz L, Catane R, Kaufman B, Beller U, Renbaum P, Gershoni-Baruch R (2001) A single nucleotide polymorphism in the RAD51 gene modifies cancer risk in BRCA2 but not BRCA1 carriers. Proc Natl Acad Sci USA 98:3232–3236CrossRefPubMed Levy-Lahad E, Lahad A, Eisenberg S, Dagan E, Paperna T, Kasinetz L, Catane R, Kaufman B, Beller U, Renbaum P, Gershoni-Baruch R (2001) A single nucleotide polymorphism in the RAD51 gene modifies cancer risk in BRCA2 but not BRCA1 carriers. Proc Natl Acad Sci USA 98:3232–3236CrossRefPubMed
7.
go back to reference Wang WW, Spurdle AB, Kolachana P, Bove B, Modan B, Ebbers SM, Suthers G, Tucker MA, Kaufman DJ, Doody MM, Tarone RE, Daly M, Levavi H, Pierce H, Chetrit A, Yechezkel GH, Chenevix-Trench G, Offit K, Godwin AK, Struewing JP (2001) A single nucleotide polymorphism in the 5′ untranslated region of RAD51 and risk of cancer among BRCA1/2 mutation carriers. Cancer Epidemiol Biomark Prev 10:955–960 Wang WW, Spurdle AB, Kolachana P, Bove B, Modan B, Ebbers SM, Suthers G, Tucker MA, Kaufman DJ, Doody MM, Tarone RE, Daly M, Levavi H, Pierce H, Chetrit A, Yechezkel GH, Chenevix-Trench G, Offit K, Godwin AK, Struewing JP (2001) A single nucleotide polymorphism in the 5′ untranslated region of RAD51 and risk of cancer among BRCA1/2 mutation carriers. Cancer Epidemiol Biomark Prev 10:955–960
8.
go back to reference Hasselbach L, Haase S, Fischer D, Kolberg HC, Sturzbecher HW (2005) Characterisation of the promoter region of the human DNA-repair gene Rad51. Eur J Gynaecol Oncol 26:589–598PubMed Hasselbach L, Haase S, Fischer D, Kolberg HC, Sturzbecher HW (2005) Characterisation of the promoter region of the human DNA-repair gene Rad51. Eur J Gynaecol Oncol 26:589–598PubMed
9.
go back to reference Kuschel B, Auranen A, McBride S, Novik KL, Antoniou A, Lipscombe JM, Day NE, Easton DF, Ponder BA, Pharoah PD, Dunning A (2002) Variants in DNA double-strand break repair genes and breast cancer susceptibility. Hum Mol Genet 11:1399–1407CrossRefPubMed Kuschel B, Auranen A, McBride S, Novik KL, Antoniou A, Lipscombe JM, Day NE, Easton DF, Ponder BA, Pharoah PD, Dunning A (2002) Variants in DNA double-strand break repair genes and breast cancer susceptibility. Hum Mol Genet 11:1399–1407CrossRefPubMed
10.
go back to reference Dufloth RM, Costa S, Schmitt F, Zeferino LC (2005) DNA repair gene polymorphisms and susceptibility to familial breast cancer in a group of patients from Campinas, Brazil. Genet Mol Res 4:771–782PubMed Dufloth RM, Costa S, Schmitt F, Zeferino LC (2005) DNA repair gene polymorphisms and susceptibility to familial breast cancer in a group of patients from Campinas, Brazil. Genet Mol Res 4:771–782PubMed
11.
go back to reference Lee KM, Choi JY, Kang C, Kang CP, Park SK, Cho H, Cho DY, Yoo KY, Noh DY, Ahn SH, Park CG, Wei Q, Kang D (2005) Genetic polymorphisms of selected DNA repair genes, estrogen and progesterone receptor status, and breast cancer risk. Clin Cancer Res 11:4620–4626CrossRefPubMed Lee KM, Choi JY, Kang C, Kang CP, Park SK, Cho H, Cho DY, Yoo KY, Noh DY, Ahn SH, Park CG, Wei Q, Kang D (2005) Genetic polymorphisms of selected DNA repair genes, estrogen and progesterone receptor status, and breast cancer risk. Clin Cancer Res 11:4620–4626CrossRefPubMed
12.
go back to reference Webb PM, Hopper JL, Newman B, Chen X, Kelemen L, Giles GG, Southey MC, Chenevix-Trench G, Spurdle AB (2005) Double-strand break repair gene polymorphisms and risk of breast or ovarian cancer. Cancer Epidemiol Biomark Prev 14:319–323CrossRef Webb PM, Hopper JL, Newman B, Chen X, Kelemen L, Giles GG, Southey MC, Chenevix-Trench G, Spurdle AB (2005) Double-strand break repair gene polymorphisms and risk of breast or ovarian cancer. Cancer Epidemiol Biomark Prev 14:319–323CrossRef
13.
go back to reference Romanowicz-Makowska H, Smolarz B, Zadrozny M, Kulig A (2006) Analysis of RAD51 polymorphism and BRCA1 mutations in Polish women with breast cancer. Exp Oncol 28:156–159PubMed Romanowicz-Makowska H, Smolarz B, Zadrozny M, Kulig A (2006) Analysis of RAD51 polymorphism and BRCA1 mutations in Polish women with breast cancer. Exp Oncol 28:156–159PubMed
14.
go back to reference Brooks J, Shore RE, Zeleniuch-Jacquotte A, Currie D, Afanasyeva Y, Koenig KL, Arslan AA, Toniolo P, Wirgin I (2008) Polymorphisms in RAD51, XRCC2, and XRCC3 are not related to breast cancer risk. Cancer Epidemiol Biomark Prev 17:1016–1019CrossRef Brooks J, Shore RE, Zeleniuch-Jacquotte A, Currie D, Afanasyeva Y, Koenig KL, Arslan AA, Toniolo P, Wirgin I (2008) Polymorphisms in RAD51, XRCC2, and XRCC3 are not related to breast cancer risk. Cancer Epidemiol Biomark Prev 17:1016–1019CrossRef
15.
go back to reference Krupa R, Synowiec E, Pawlowska E, Morawiec Z, Sobczuk A, Zadrozny M, Wozniak K, Blasiak J (2009) Polymorphism of the homologous recombination repair genes RAD51 and XRCC3 in breast cancer. Exp Mol Pathol 87:32–35CrossRefPubMed Krupa R, Synowiec E, Pawlowska E, Morawiec Z, Sobczuk A, Zadrozny M, Wozniak K, Blasiak J (2009) Polymorphism of the homologous recombination repair genes RAD51 and XRCC3 in breast cancer. Exp Mol Pathol 87:32–35CrossRefPubMed
16.
go back to reference Jara L, Dubois K, Gaete D, de Mayo T, Ratkevicius N, Bravo T, Margarit S, Blanco R, Gomez F, Waugh E, Peralta O, Reyes JM, Ibanez G, Gonzalez-Hormazabal P (2010) Variants in DNA double-strand break repair genes and risk of familial breast cancer in a South American population. Breast Cancer Res Treat Jara L, Dubois K, Gaete D, de Mayo T, Ratkevicius N, Bravo T, Margarit S, Blanco R, Gomez F, Waugh E, Peralta O, Reyes JM, Ibanez G, Gonzalez-Hormazabal P (2010) Variants in DNA double-strand break repair genes and risk of familial breast cancer in a South American population. Breast Cancer Res Treat
17.
go back to reference Antoniou AC, Sinilnikova OM, Simard J, Leone M, Dumont M, Neuhausen SL, Struewing JP, Stoppa-Lyonnet D, Barjhoux L, Hughes DJ, Coupier I, Belotti M, Lasset C, Bonadona V, Bignon YJ, Rebbeck TR, Wagner T, Lynch HT, Domchek SM, Nathanson KL, Garber JE, Weitzel J, Narod SA, Tomlinson G, Olopade OI, Godwin A, Isaacs C, Jakubowska A, Lubinski J, Gronwald J, Gorski B, Byrski T, Huzarski T, Peock S, Cook M, Baynes C, Murray A, Rogers M, Daly PA, Dorkins H, Schmutzler RK, Versmold B, Engel C, Meindl A, Arnold N, Niederacher D, Deissler H, Spurdle AB, Chen X, Waddell N, Cloonan N, Kirchhoff T, Offit K, Friedman E, Kaufmann B, Laitman Y, Galore G, Rennert G, Lejbkowicz F, Raskin L, Andrulis IL, Ilyushik E, Ozcelik H, Devilee P, Vreeswijk MP, Greene MH, Prindiville SA, Osorio A, Benitez J, Zikan M, Szabo CI, Kilpivaara O, Nevanlinna H, Hamann U, Durocher F, Arason A, Couch FJ, Easton DF, Chenevix-Trench G (2007) RAD51 135G–>C modifies breast cancer risk among BRCA2 mutation carriers: results from a combined analysis of 19 studies. Am J Hum Genet 81:1186–1200 Antoniou AC, Sinilnikova OM, Simard J, Leone M, Dumont M, Neuhausen SL, Struewing JP, Stoppa-Lyonnet D, Barjhoux L, Hughes DJ, Coupier I, Belotti M, Lasset C, Bonadona V, Bignon YJ, Rebbeck TR, Wagner T, Lynch HT, Domchek SM, Nathanson KL, Garber JE, Weitzel J, Narod SA, Tomlinson G, Olopade OI, Godwin A, Isaacs C, Jakubowska A, Lubinski J, Gronwald J, Gorski B, Byrski T, Huzarski T, Peock S, Cook M, Baynes C, Murray A, Rogers M, Daly PA, Dorkins H, Schmutzler RK, Versmold B, Engel C, Meindl A, Arnold N, Niederacher D, Deissler H, Spurdle AB, Chen X, Waddell N, Cloonan N, Kirchhoff T, Offit K, Friedman E, Kaufmann B, Laitman Y, Galore G, Rennert G, Lejbkowicz F, Raskin L, Andrulis IL, Ilyushik E, Ozcelik H, Devilee P, Vreeswijk MP, Greene MH, Prindiville SA, Osorio A, Benitez J, Zikan M, Szabo CI, Kilpivaara O, Nevanlinna H, Hamann U, Durocher F, Arason A, Couch FJ, Easton DF, Chenevix-Trench G (2007) RAD51 135G–>C modifies breast cancer risk among BRCA2 mutation carriers: results from a combined analysis of 19 studies. Am J Hum Genet 81:1186–1200
18.
go back to reference Blasiak J, Przybylowska K, Czechowska A, Zadrozny M, Pertynski T, Rykala J, Kolacinska A, Morawiec Z, Drzewoski J (2003) Analysis of the G/C polymorphism in the 5′-untranslated region of the RAD51 gene in breast cancer. Acta Biochim Pol 50:249–253PubMed Blasiak J, Przybylowska K, Czechowska A, Zadrozny M, Pertynski T, Rykala J, Kolacinska A, Morawiec Z, Drzewoski J (2003) Analysis of the G/C polymorphism in the 5′-untranslated region of the RAD51 gene in breast cancer. Acta Biochim Pol 50:249–253PubMed
19.
go back to reference Sliwinski T, Krupa R, Majsterek I, Rykala J, Kolacinska A, Morawiec Z, Drzewoski J, Zadrozny M, Blasiak J (2005) Polymorphisms of the BRCA2 and RAD51 genes in breast cancer. Breast Cancer Res Treat 94:105–109CrossRefPubMed Sliwinski T, Krupa R, Majsterek I, Rykala J, Kolacinska A, Morawiec Z, Drzewoski J, Zadrozny M, Blasiak J (2005) Polymorphisms of the BRCA2 and RAD51 genes in breast cancer. Breast Cancer Res Treat 94:105–109CrossRefPubMed
20.
go back to reference Wang Z, Fu Y, Tang C, Lu S, Chu WM (2009) SULT1A1 R213H polymorphism and breast cancer risk: a meta-analysis based on 8,454 cases and 11,800 controls. Breast Cancer Res Treat Wang Z, Fu Y, Tang C, Lu S, Chu WM (2009) SULT1A1 R213H polymorphism and breast cancer risk: a meta-analysis based on 8,454 cases and 11,800 controls. Breast Cancer Res Treat
21.
go back to reference Wang Z, Cui D, Lu W NBS1 8360G > C polymorphism is associated with breast cancer risk: a meta-analysis. (2010) Breast Cancer Res Treat Wang Z, Cui D, Lu W NBS1 8360G > C polymorphism is associated with breast cancer risk: a meta-analysis. (2010) Breast Cancer Res Treat
22.
go back to reference Lau J, Ioannidis JP, Schmid CH (1997) Quantitative synthesis in systematic reviews. Ann Intern Med 127:820–826PubMed Lau J, Ioannidis JP, Schmid CH (1997) Quantitative synthesis in systematic reviews. Ann Intern Med 127:820–826PubMed
23.
go back to reference Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748PubMed Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748PubMed
24.
25.
go back to reference Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634PubMed Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634PubMed
26.
go back to reference Thompson LH, Schild D (2001) Homologous recombinational repair of DNA ensures mammalian chromosome stability. Mutat Res 477:131–153PubMed Thompson LH, Schild D (2001) Homologous recombinational repair of DNA ensures mammalian chromosome stability. Mutat Res 477:131–153PubMed
27.
go back to reference Rodrigue A, Lafrance M, Gauthier MC, McDonald D, Hendzel M, West SC, Jasin M, Masson JY (2006) Interplay between human DNA repair proteins at a unique double-strand break in vivo. EMBO J 25:222–231CrossRefPubMed Rodrigue A, Lafrance M, Gauthier MC, McDonald D, Hendzel M, West SC, Jasin M, Masson JY (2006) Interplay between human DNA repair proteins at a unique double-strand break in vivo. EMBO J 25:222–231CrossRefPubMed
28.
go back to reference Jakubowska A, Gronwald J, Menkiszak J, Gorski B, Huzarski T, Byrski T, Edler L, Lubinski J, Scott RJ, Hamann U (2007) The RAD51 135 G>C polymorphism modifies breast cancer and ovarian cancer risk in Polish BRCA1 mutation carriers. Cancer Epidemiol Biomark Prev 16:270–275CrossRef Jakubowska A, Gronwald J, Menkiszak J, Gorski B, Huzarski T, Byrski T, Edler L, Lubinski J, Scott RJ, Hamann U (2007) The RAD51 135 G>C polymorphism modifies breast cancer and ovarian cancer risk in Polish BRCA1 mutation carriers. Cancer Epidemiol Biomark Prev 16:270–275CrossRef
29.
go back to reference Gray NK (1998) Translational control by repressor proteins binding to the 5′UTR of mRNAs. Methods Mol Biol 77:379–397PubMed Gray NK (1998) Translational control by repressor proteins binding to the 5′UTR of mRNAs. Methods Mol Biol 77:379–397PubMed
Metadata
Title
RAD51 135G>C polymorphism contributes to breast cancer susceptibility: a meta-analysis involving 26,444 subjects
Authors
Zhanwei Wang
Hairong Dong
Yuanyuan Fu
Haixia Ding
Publication date
01-12-2010
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2010
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-010-0885-0

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