Tumor Biol. DOI 10.1007/s13277-014-2078-7
RESEARCH ARTICLE
CD243 gene polymorphism significantly associated with breast cancer susceptibility Weirong Yao & Rongzeng Yan & Lin Ma & Huiping Wan & Yanmin Yu & Xia Cheng & Yingliang Li
Received: 1 April 2014 / Accepted: 7 May 2014 # International Society of Oncology and BioMarkers (ISOBM) 2014
Abstract We aimed to obtain a summary risk estimate for CD243 gene polymorphism associated with breast cancer. A total of nine case–control studies, including 5,073 cancer patients and 7,498 control subjects, were pooled in our fixed effects meta-analysis of the association between CD243 gene polymorphism and risk of breast cancer. All data were analyzed by using Stata software (version 12.0). We found significant risk effects under TT vs. TC+CC genetic model [odds ratio (OR)=1.09, 95 % confidence interval (CI)=1.01–1.18, P=0.516], but not in other comparisons. Stratifying the pooled data by ethnicity and source of controls revealed that the association between the T allele and an increased risk of breast cancer was more pronounced among Asians (TT vs. CC: OR=1.26, 95 % CI=1.02–1.57, P=0.720; TT vs. TC+ CC: OR=1.31, 95 % CI=1.07–1.61, P=0.708) and hospitalbased studies (TT vs. CC: OR=1.25, 95 % CI=1.02–1.53, P= 0.877; TT vs. TC+CC: OR=1.27, 95 % CI=1.05–1.53, P= 0.540). No notable heterogeneity was indicated across studies. Our meta-analysis demonstrates that CD243 gene
Weirong Yao and Rongzeng Yan are co-first authors. W. Yao : L. Ma (*) Department of Radiation Oncology, Chinese PLA General Hospital, Beijing, China e-mail: [email protected] W. Yao : H. Wan : Y. Yu : X. Cheng Department of Oncology, People’s Hospital of Jiangxi Province, Nanchang, China R. Yan Chinese People’s Armed Police Forces Jiangxi General Hospital, Nanchang, China Y. Li (*) Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China e-mail: [email protected]
polymorphism may act as a predisposition factor for breast cancer, particularly in Asian populations. Keywords CD243 polymorphism . Breast cancer . Risk
Introduction Breast cancer is the most malignant disease among women [1], and more than one million new cases are diagnosed each year throughout the world [2]. The etiology of this exciting trend is speculatively the continuing use of screening mammography, interventions of breast cancer prevention, and a decreased use of postmenopausal hormone replacement therapy [3]. Genetic variants at multiple susceptibility loci have shown to play a significant role in the malignant progression of breast cancer, prognosis of the patients, and reactions to specific treatments and certain therapies [4–7]. CD243 is related to these phenotypes, and its genetic products should account for the resistance against the effective chemotherapeutics for this disease [8]. The CD243 is an important member of the adenosine triphosphate-binding cassette protein superfamily of membrane transporters that function as an ATP-dependent drug efflux pump with a broad substrate specificity, protecting cells from toxic metabolites [9, 10]. Overexpression of this protein is significantly associated with multidrug resistance phenotype in several cancers, including childhood acute lymphoblastic leukemia [11], small cell lung cancer [12], colon cancer [13], and breast cancer [14, 15]. The highly polymorphic gene has at least 40 single-nucleotide polymorphisms (SNPs) consisting of 64 statistically inferred haplotypes [16]. The sequence variation in exon 26 has been the most common SNP associated with therapeutic outcomes in breast cancer treatment [17]. A number of studies representing various ethnicities have focused on the predisposition role of CD243
Tumor Biol.
gene polymorphism in breast cancer [18–21]. However, there has been no consistent result received yet. The association of CD243 gene polymorphism with risk of breast cancer also stimulates great interest in several meta-analyses [22–26], where the combined data are either inaccurate or incomprehensive, leading to considerable controversy as well. A plausible hypothesis that can reconcile the aforementioned discrepancy is that CD243 gene polymorphism is significantly associated with risk of breast cancer. To test this hypothesis, we analyzed all available data to date by use of a meta-analysis.
Materials and methods Literature search To identify the early released studies addressing the genetic association of CD243 gene polymorphism and breast cancer, we undertook a comprehensive literature search in the PubMed, Web of Science, and CNKI databases, using the following search terms and keywords: “CD243,” “SNP,” or “polymorphism” and “breast cancer” or “breast carcinoma.” The identification of eligible studies was conducted from June to October 2013. We also manually searched each of the eligible studies in an attempt to identify additional data.
The significance of the pooled OR was determined with a Z test. Stratified analyses by ethnicity and control source (if the source of control was not clearly stated in the original article, we merged them into the “other” group) were performed to assess the risk effects for each subgroup. Between-study heterogeneity assumption was measured using Cochran’s Q test. Either a random effects model (DerSimonian-Laird) [27] or a fixed effects model (Mantel-Haenszel) [28] was used to calculate pooled OR estimates. The fixed effects model was selected when Cochran’s Q test indicated no significant heterogeneity; otherwise, the random effects model was employed. The one-way sensitivity analysis was performed to assess the stability of the results. Data on the CD243 gene polymorphism in controls were checked for departure from HardyWeinberg equilibrium (HWE). An estimate of potential publication bias among the included studies was conducted by Begg’s test and Egger’s test [29]. All statistical tests used a two-sided P
RESEARCH ARTICLE
CD243 gene polymorphism significantly associated with breast cancer susceptibility Weirong Yao & Rongzeng Yan & Lin Ma & Huiping Wan & Yanmin Yu & Xia Cheng & Yingliang Li
Received: 1 April 2014 / Accepted: 7 May 2014 # International Society of Oncology and BioMarkers (ISOBM) 2014
Abstract We aimed to obtain a summary risk estimate for CD243 gene polymorphism associated with breast cancer. A total of nine case–control studies, including 5,073 cancer patients and 7,498 control subjects, were pooled in our fixed effects meta-analysis of the association between CD243 gene polymorphism and risk of breast cancer. All data were analyzed by using Stata software (version 12.0). We found significant risk effects under TT vs. TC+CC genetic model [odds ratio (OR)=1.09, 95 % confidence interval (CI)=1.01–1.18, P=0.516], but not in other comparisons. Stratifying the pooled data by ethnicity and source of controls revealed that the association between the T allele and an increased risk of breast cancer was more pronounced among Asians (TT vs. CC: OR=1.26, 95 % CI=1.02–1.57, P=0.720; TT vs. TC+ CC: OR=1.31, 95 % CI=1.07–1.61, P=0.708) and hospitalbased studies (TT vs. CC: OR=1.25, 95 % CI=1.02–1.53, P= 0.877; TT vs. TC+CC: OR=1.27, 95 % CI=1.05–1.53, P= 0.540). No notable heterogeneity was indicated across studies. Our meta-analysis demonstrates that CD243 gene
Weirong Yao and Rongzeng Yan are co-first authors. W. Yao : L. Ma (*) Department of Radiation Oncology, Chinese PLA General Hospital, Beijing, China e-mail: [email protected] W. Yao : H. Wan : Y. Yu : X. Cheng Department of Oncology, People’s Hospital of Jiangxi Province, Nanchang, China R. Yan Chinese People’s Armed Police Forces Jiangxi General Hospital, Nanchang, China Y. Li (*) Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China e-mail: [email protected]
polymorphism may act as a predisposition factor for breast cancer, particularly in Asian populations. Keywords CD243 polymorphism . Breast cancer . Risk
Introduction Breast cancer is the most malignant disease among women [1], and more than one million new cases are diagnosed each year throughout the world [2]. The etiology of this exciting trend is speculatively the continuing use of screening mammography, interventions of breast cancer prevention, and a decreased use of postmenopausal hormone replacement therapy [3]. Genetic variants at multiple susceptibility loci have shown to play a significant role in the malignant progression of breast cancer, prognosis of the patients, and reactions to specific treatments and certain therapies [4–7]. CD243 is related to these phenotypes, and its genetic products should account for the resistance against the effective chemotherapeutics for this disease [8]. The CD243 is an important member of the adenosine triphosphate-binding cassette protein superfamily of membrane transporters that function as an ATP-dependent drug efflux pump with a broad substrate specificity, protecting cells from toxic metabolites [9, 10]. Overexpression of this protein is significantly associated with multidrug resistance phenotype in several cancers, including childhood acute lymphoblastic leukemia [11], small cell lung cancer [12], colon cancer [13], and breast cancer [14, 15]. The highly polymorphic gene has at least 40 single-nucleotide polymorphisms (SNPs) consisting of 64 statistically inferred haplotypes [16]. The sequence variation in exon 26 has been the most common SNP associated with therapeutic outcomes in breast cancer treatment [17]. A number of studies representing various ethnicities have focused on the predisposition role of CD243
Tumor Biol.
gene polymorphism in breast cancer [18–21]. However, there has been no consistent result received yet. The association of CD243 gene polymorphism with risk of breast cancer also stimulates great interest in several meta-analyses [22–26], where the combined data are either inaccurate or incomprehensive, leading to considerable controversy as well. A plausible hypothesis that can reconcile the aforementioned discrepancy is that CD243 gene polymorphism is significantly associated with risk of breast cancer. To test this hypothesis, we analyzed all available data to date by use of a meta-analysis.
Materials and methods Literature search To identify the early released studies addressing the genetic association of CD243 gene polymorphism and breast cancer, we undertook a comprehensive literature search in the PubMed, Web of Science, and CNKI databases, using the following search terms and keywords: “CD243,” “SNP,” or “polymorphism” and “breast cancer” or “breast carcinoma.” The identification of eligible studies was conducted from June to October 2013. We also manually searched each of the eligible studies in an attempt to identify additional data.
The significance of the pooled OR was determined with a Z test. Stratified analyses by ethnicity and control source (if the source of control was not clearly stated in the original article, we merged them into the “other” group) were performed to assess the risk effects for each subgroup. Between-study heterogeneity assumption was measured using Cochran’s Q test. Either a random effects model (DerSimonian-Laird) [27] or a fixed effects model (Mantel-Haenszel) [28] was used to calculate pooled OR estimates. The fixed effects model was selected when Cochran’s Q test indicated no significant heterogeneity; otherwise, the random effects model was employed. The one-way sensitivity analysis was performed to assess the stability of the results. Data on the CD243 gene polymorphism in controls were checked for departure from HardyWeinberg equilibrium (HWE). An estimate of potential publication bias among the included studies was conducted by Begg’s test and Egger’s test [29]. All statistical tests used a two-sided P
