Skip to main content
Top
Published in: Breast Cancer Research and Treatment 1/2010

01-02-2010 | Epidemiology

Differential effects of MDM2 SNP309 polymorphism on breast cancer risk along with race: a meta-analysis

Authors: Konstantinos P. Economopoulos, Theodoros N. Sergentanis

Published in: Breast Cancer Research and Treatment | Issue 1/2010

Login to get access

Abstract

MDM2 SNP309 is a single nucleotide T > G polymorphism present in intron 1 of the MDM2 gene. A variety of case–control studies have been published evaluating the association between MDM2 SNP309 and breast cancer risk. However, the published studies, as well as the subsequent meta-analyses, have yielded contradictory results. This meta-analysis aims to examine whether MDM SNP309 polymorphism may exert a differential effect on breast cancer risk along with race. Eligible articles were identified by a search of MEDLINE, Cochrane and EMBASE bibliographical databases for the period July 1993 to June 2009; 16 case–control studies were eligible (12,986 breast cancer cases, 12,993 controls). Subanalyses in case–control studies conducted on Chinese (3 studies, 892 cases, 1,435 controls) and non-Chinese populations (13 studies, 12,094 cases, 11,558 controls) were performed. All pooled odds ratios (ORs) were derived from fixed-effects models given that the between-study heterogeneity was not statistically significant. Subanalysis on Chinese subjects demonstrated that GT and GG genotype were associated with increased breast cancer risk (pooled OR = 1.272, 95% CI 1.025–1.578 and pooled OR = 1.323, 95% CI 1.034–1.694, respectively); as a result the overall effect of the G allele was statistically significant (pooled OR = 1.287, 95% CI 1.048–1.579). On the contrary, no significant associations between MDM2 SNP309 status and breast cancer risk were demonstrated in non-Chinese populations. In conclusion, the association between MDM2 SNP309 and breast cancer is modified by race. MDM2 SNP309 represents a risk factor for breast cancer in Chinese women but not in non-Chinese women. This phenomenon is analogous to that described in the context of lung cancer.
Literature
2.
go back to reference Bouska A, Eischen CM (2009) Mdm2 affects genome stability independent of p53. Cancer Res 69:1697–1701CrossRefPubMed Bouska A, Eischen CM (2009) Mdm2 affects genome stability independent of p53. Cancer Res 69:1697–1701CrossRefPubMed
3.
go back to reference Agrawal A, Yang J, Murphy RF, Agrawal DK (2006) Regulation of the p14ARF-Mdm2-p53 pathway: an overview in breast cancer. Exp Mol Pathol 81:115–122CrossRefPubMed Agrawal A, Yang J, Murphy RF, Agrawal DK (2006) Regulation of the p14ARF-Mdm2-p53 pathway: an overview in breast cancer. Exp Mol Pathol 81:115–122CrossRefPubMed
4.
go back to reference Bond GL, Hu W, Bond EE, Robins H, Lutzker SG, Arva NC, Bargonetti J, Bartel F, Taubert H, Wuerl P, Onel K, Yip L, Hwang SJ, Strong LC, Lozano G, Levine AJ (2004) A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. Cell 119:591–602CrossRefPubMed Bond GL, Hu W, Bond EE, Robins H, Lutzker SG, Arva NC, Bargonetti J, Bartel F, Taubert H, Wuerl P, Onel K, Yip L, Hwang SJ, Strong LC, Lozano G, Levine AJ (2004) A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. Cell 119:591–602CrossRefPubMed
5.
go back to reference Boersma BJ, Howe TM, Goodman JE, Yfantis HG, Lee DH, Chanock SJ, Ambs S (2006) Association of breast cancer outcome with status of p53 and MDM2 SNP309. J Natl Cancer Inst 98:911–919PubMedCrossRef Boersma BJ, Howe TM, Goodman JE, Yfantis HG, Lee DH, Chanock SJ, Ambs S (2006) Association of breast cancer outcome with status of p53 and MDM2 SNP309. J Natl Cancer Inst 98:911–919PubMedCrossRef
6.
go back to reference Campbell IG, Eccles DM, Choong DY (2006) No association of the MDM2 SNP309 polymorphism with risk of breast or ovarian cancer. Cancer Lett 240:195–197CrossRefPubMed Campbell IG, Eccles DM, Choong DY (2006) No association of the MDM2 SNP309 polymorphism with risk of breast or ovarian cancer. Cancer Lett 240:195–197CrossRefPubMed
7.
go back to reference Millikan RC, Heard K, Winkel S, Hill EJ, Massa B, Mayes L, Williams P, Holston R, Conway K, Edmiston S, de Cotret AR (2006) No association between the MDM2-309 T/G promoter polymorphism and breast cancer in African-Americans or Whites. Cancer Epidemiol Biomarkers Prev 15:175–177CrossRefPubMed Millikan RC, Heard K, Winkel S, Hill EJ, Massa B, Mayes L, Williams P, Holston R, Conway K, Edmiston S, de Cotret AR (2006) No association between the MDM2-309 T/G promoter polymorphism and breast cancer in African-Americans or Whites. Cancer Epidemiol Biomarkers Prev 15:175–177CrossRefPubMed
8.
go back to reference Ma H, Hu Z, Zhai X, Wang S, Wang X, Qin J, Jin G, Liu J, Wei Q, Shen H (2006) Polymorphisms in the MDM2 promoter and risk of breast cancer: a case–control analysis in a Chinese population. Cancer Lett 240:261–267CrossRefPubMed Ma H, Hu Z, Zhai X, Wang S, Wang X, Qin J, Jin G, Liu J, Wei Q, Shen H (2006) Polymorphisms in the MDM2 promoter and risk of breast cancer: a case–control analysis in a Chinese population. Cancer Lett 240:261–267CrossRefPubMed
9.
go back to reference Copson ER, White HE, Blaydes JP, Robinson DO, Johnson PW, Eccles DM (2006) Influence of the MDM2 single nucleotide polymorphism SNP309 on tumour development in BRCA1 mutation carriers. BMC Cancer 6:80CrossRefPubMed Copson ER, White HE, Blaydes JP, Robinson DO, Johnson PW, Eccles DM (2006) Influence of the MDM2 single nucleotide polymorphism SNP309 on tumour development in BRCA1 mutation carriers. BMC Cancer 6:80CrossRefPubMed
10.
go back to reference Petenkaya A, Bozkurt B, Akilli-Ozturk O, Kaya HS, Gur-Dedeoglu B, Yulug IG (2006) Lack of association between the MDM2-SNP309 polymorphism and breast cancer risk. Anticancer Res 26:4975–4977PubMed Petenkaya A, Bozkurt B, Akilli-Ozturk O, Kaya HS, Gur-Dedeoglu B, Yulug IG (2006) Lack of association between the MDM2-SNP309 polymorphism and breast cancer risk. Anticancer Res 26:4975–4977PubMed
11.
go back to reference Wilkening S, Bermejo JL, Burwinkel B, Klaes R, Bartram CR, Meindl A, Bugert P, Schmutzler RK, Wappenschmidt B, Untch M, Hemminki K, Forsti A (2006) The single nucleotide polymorphism IVS1 + 309 in mouse double minute 2 does not affect risk of familial breast cancer. Cancer Res 66:646–648CrossRefPubMed Wilkening S, Bermejo JL, Burwinkel B, Klaes R, Bartram CR, Meindl A, Bugert P, Schmutzler RK, Wappenschmidt B, Untch M, Hemminki K, Forsti A (2006) The single nucleotide polymorphism IVS1 + 309 in mouse double minute 2 does not affect risk of familial breast cancer. Cancer Res 66:646–648CrossRefPubMed
12.
go back to reference Cox DG, Deer D, Guo Q, Tworoger SS, Hankinson SE, Hunter DJ, De Vivo I (2007) The p53 Arg72Pro and MDM2-309 polymorphisms and risk of breast cancer in the nurses’ health studies. Cancer Causes Control 18:621–625CrossRefPubMed Cox DG, Deer D, Guo Q, Tworoger SS, Hankinson SE, Hunter DJ, De Vivo I (2007) The p53 Arg72Pro and MDM2-309 polymorphisms and risk of breast cancer in the nurses’ health studies. Cancer Causes Control 18:621–625CrossRefPubMed
13.
go back to reference Wasielewski M, Nagel JH, Brekelmans C, Klijn JG, van den Ouweland A, Meijers-Heijboer H, Schutte M (2007) MDM2 SNP309 accelerates familial breast carcinogenesis independently of estrogen signaling. Breast Cancer Res Treat 104:153–157CrossRefPubMed Wasielewski M, Nagel JH, Brekelmans C, Klijn JG, van den Ouweland A, Meijers-Heijboer H, Schutte M (2007) MDM2 SNP309 accelerates familial breast carcinogenesis independently of estrogen signaling. Breast Cancer Res Treat 104:153–157CrossRefPubMed
14.
go back to reference Schmidt MK, Reincke S, Broeks A, Braaf LM, Hogervorst FB, Tollenaar RA, Johnson N, Fletcher O, Peto J, Tommiska J, Blomqvist C, Nevanlinna HA, Healey CS, Dunning AM, Pharoah PD, Easton DF, Dork T, Van’t Veer LJ (2007) Do MDM2 SNP309 and TP53 R72P interact in breast cancer susceptibility? A large pooled series from the breast cancer association consortium. Cancer Res 67:9584–9590CrossRefPubMed Schmidt MK, Reincke S, Broeks A, Braaf LM, Hogervorst FB, Tollenaar RA, Johnson N, Fletcher O, Peto J, Tommiska J, Blomqvist C, Nevanlinna HA, Healey CS, Dunning AM, Pharoah PD, Easton DF, Dork T, Van’t Veer LJ (2007) Do MDM2 SNP309 and TP53 R72P interact in breast cancer susceptibility? A large pooled series from the breast cancer association consortium. Cancer Res 67:9584–9590CrossRefPubMed
15.
go back to reference Yarden RI, Friedman E, Metsuyanim S, Olender T, Ben-Asher E, Papa MZ (2008) MDM2 SNP309 accelerates breast and ovarian carcinogenesis in BRCA1 and BRCA2 carriers of Jewish-Ashkenazi descent. Breast Cancer Res Treat 111:497–504CrossRefPubMed Yarden RI, Friedman E, Metsuyanim S, Olender T, Ben-Asher E, Papa MZ (2008) MDM2 SNP309 accelerates breast and ovarian carcinogenesis in BRCA1 and BRCA2 carriers of Jewish-Ashkenazi descent. Breast Cancer Res Treat 111:497–504CrossRefPubMed
16.
go back to reference Lum SS, Chua HW, Li H, Li WF, Rao N, Wei J, Shao Z, Sabapathy K (2008) MDM2 SNP309 G allele increases risk but the T allele is associated with earlier onset age of sporadic breast cancers in the Chinese population. Carcinogenesis 29:754–761CrossRefPubMed Lum SS, Chua HW, Li H, Li WF, Rao N, Wei J, Shao Z, Sabapathy K (2008) MDM2 SNP309 G allele increases risk but the T allele is associated with earlier onset age of sporadic breast cancers in the Chinese population. Carcinogenesis 29:754–761CrossRefPubMed
17.
go back to reference Krekac D, Brozkova K, Knoflickova D, Hrstka R, Muller P, Nenutil R, Vojtesek B (2008) MDM2SNP309 does not associate with elevated MDM2 protein expression or breast cancer risk. Oncology 74:84–87CrossRefPubMed Krekac D, Brozkova K, Knoflickova D, Hrstka R, Muller P, Nenutil R, Vojtesek B (2008) MDM2SNP309 does not associate with elevated MDM2 protein expression or breast cancer risk. Oncology 74:84–87CrossRefPubMed
18.
go back to reference Paulin FE, O’Neill M, McGregor G, Cassidy A, Ashfield A, Ali CW, Munro AJ, Baker L, Purdie CA, Lane DP, Thompson AM (2008) MDM2 SNP309 is associated with high grade node positive breast tumours and is in linkage disequilibrium with a novel MDM2 intron 1 polymorphism. BMC Cancer 8:281CrossRefPubMed Paulin FE, O’Neill M, McGregor G, Cassidy A, Ashfield A, Ali CW, Munro AJ, Baker L, Purdie CA, Lane DP, Thompson AM (2008) MDM2 SNP309 is associated with high grade node positive breast tumours and is in linkage disequilibrium with a novel MDM2 intron 1 polymorphism. BMC Cancer 8:281CrossRefPubMed
19.
go back to reference Sun YF, Leu JD, Chen SM, Lin IF, Lee YJ (2009) Results based on 124 cases of breast cancer and 97 controls from Taiwan suggest that the single nucleotide polymorphism (SNP309) in the MDM2 gene promoter is associated with earlier onset and increased risk of breast cancer. BMC Cancer 9:13CrossRefPubMed Sun YF, Leu JD, Chen SM, Lin IF, Lee YJ (2009) Results based on 124 cases of breast cancer and 97 controls from Taiwan suggest that the single nucleotide polymorphism (SNP309) in the MDM2 gene promoter is associated with earlier onset and increased risk of breast cancer. BMC Cancer 9:13CrossRefPubMed
20.
go back to reference Singh V, Rastogi N, Mathur N, Singh K, Singh MP (2008) Association of polymorphism in MDM-2 and p53 genes with breast cancer risk in Indian women. Ann Epidemiol 18:48–57CrossRefPubMed Singh V, Rastogi N, Mathur N, Singh K, Singh MP (2008) Association of polymorphism in MDM-2 and p53 genes with breast cancer risk in Indian women. Ann Epidemiol 18:48–57CrossRefPubMed
21.
go back to reference Hu Z, Jin G, Wang L, Chen F, Wang X, Shen H (2007) MDM2 promoter polymorphism SNP309 contributes to tumor susceptibility: evidence from 21 case–control studies. Cancer Epidemiol Biomarkers Prev 16:2717–2723CrossRefPubMed Hu Z, Jin G, Wang L, Chen F, Wang X, Shen H (2007) MDM2 promoter polymorphism SNP309 contributes to tumor susceptibility: evidence from 21 case–control studies. Cancer Epidemiol Biomarkers Prev 16:2717–2723CrossRefPubMed
22.
go back to reference Wilkening S, Bermejo JL, Hemminki K (2007) MDM2 SNP309 and cancer risk: a combined analysis. Carcinogenesis 28:2262–2267CrossRefPubMed Wilkening S, Bermejo JL, Hemminki K (2007) MDM2 SNP309 and cancer risk: a combined analysis. Carcinogenesis 28:2262–2267CrossRefPubMed
23.
go back to reference Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560CrossRefPubMed Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560CrossRefPubMed
24.
go back to reference Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101CrossRefPubMed Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101CrossRefPubMed
25.
go back to reference Nechushtan H, Hamburger T, Mendelson S, Kadouri L, Sharon N, Pikarsky E, Peretz T (2009) Effects of the single nucleotide polymorphism at MDM2 309 on breast cancer patients with/without BRCA1/2 mutations. BMC Cancer 9:60CrossRefPubMed Nechushtan H, Hamburger T, Mendelson S, Kadouri L, Sharon N, Pikarsky E, Peretz T (2009) Effects of the single nucleotide polymorphism at MDM2 309 on breast cancer patients with/without BRCA1/2 mutations. BMC Cancer 9:60CrossRefPubMed
26.
go back to reference Bond GL, Hirshfield KM, Kirchhoff T, Alexe G, Bond EE, Robins H, Bartel F, Taubert H, Wuerl P, Hait W, Toppmeyer D, Offit K, Levine AJ (2006) MDM2 SNP309 accelerates tumor formation in a gender-specific and hormone-dependent manner. Cancer Res 66:5104–5110CrossRefPubMed Bond GL, Hirshfield KM, Kirchhoff T, Alexe G, Bond EE, Robins H, Bartel F, Taubert H, Wuerl P, Hait W, Toppmeyer D, Offit K, Levine AJ (2006) MDM2 SNP309 accelerates tumor formation in a gender-specific and hormone-dependent manner. Cancer Res 66:5104–5110CrossRefPubMed
27.
go back to reference Gui XH, Qiu LX, Zhang HF, Zhang DP, Zhong WZ, Li J, Xiao YL (2009) MDM2 309 T/G polymorphism is associated with lung cancer risk among Asians. Eur J Cancer 45(11):2023–2026 Gui XH, Qiu LX, Zhang HF, Zhang DP, Zhong WZ, Li J, Xiao YL (2009) MDM2 309 T/G polymorphism is associated with lung cancer risk among Asians. Eur J Cancer 45(11):2023–2026
28.
go back to reference Bueso-Ramos CE, Manshouri T, Haidar MA, Yang Y, McCown P, Ordonez N, Glassman A, Sneige N, Albitar M (1996) Abnormal expression of MDM-2 in breast carcinomas. Breast Cancer Res Treat 37:179–188CrossRefPubMed Bueso-Ramos CE, Manshouri T, Haidar MA, Yang Y, McCown P, Ordonez N, Glassman A, Sneige N, Albitar M (1996) Abnormal expression of MDM-2 in breast carcinomas. Breast Cancer Res Treat 37:179–188CrossRefPubMed
29.
go back to reference Bai J, Dai J, Yu H, Shen H, Chen F (2009) Cigarette smoking, MDM2 SNP309, gene-environment interactions, and lung cancer risk: a meta-analysis. J Toxicol Environ Health A 72:677–682CrossRefPubMed Bai J, Dai J, Yu H, Shen H, Chen F (2009) Cigarette smoking, MDM2 SNP309, gene-environment interactions, and lung cancer risk: a meta-analysis. J Toxicol Environ Health A 72:677–682CrossRefPubMed
30.
go back to reference Casey PM, P.M. Cerhan PM, Pruthi S (2008) Oral contraceptive use and risk of breast cancer. Mayo Clin Proc 83:86–90; quiz 90-81 Casey PM, P.M. Cerhan PM, Pruthi S (2008) Oral contraceptive use and risk of breast cancer. Mayo Clin Proc 83:86–90; quiz 90-81
31.
go back to reference Cleary MP, Grossmann ME (2009) Minireview: obesity and breast cancer: the estrogen connection. Endocrinology 150:2537–2542CrossRefPubMed Cleary MP, Grossmann ME (2009) Minireview: obesity and breast cancer: the estrogen connection. Endocrinology 150:2537–2542CrossRefPubMed
Metadata
Title
Differential effects of MDM2 SNP309 polymorphism on breast cancer risk along with race: a meta-analysis
Authors
Konstantinos P. Economopoulos
Theodoros N. Sergentanis
Publication date
01-02-2010
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 1/2010
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-009-0467-1

Other articles of this Issue 1/2010

Breast Cancer Research and Treatment 1/2010 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine