MDM2 309 T/G polymorphism is associated with lung cancer risk among Asians

Published data on the association between MDM2 309 T/G polymorphism and lung cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of eight studies including 6063 cases and 6678 controls were involved in this meta-analysis. Overall, significantly elevated lung cancer risk was associated with GG variant genotype in recessive model when all the eligible studies were pooled into the meta-analysis (OR = 1.17; 95% CI = 1.02–1.34; P_{heterogeneity} = 0.06). In the subgroup analysis by ethnicity, significantly increased risks were found among Asians for TG versus TT (OR = 1.20; 95% CI = 1.05–1.37; P_{heterogeneity} = 0.30), GG versus TT (OR = 1.34; 95% CI = 1.01–1.79; P_{heterogeneity} = 0.03) and dominant model (OR = 1.26; 95% CI = 1.11–1.43; P_{heterogeneity} = 0.14). However, no significant associations were found in both Europeans and Africans for all genetic models. This meta-analysis suggests that the MDM2 309G allele is a low-penetrant risk factor for developing lung cancer in Asians.     

Induction of apoptosis by <Emphasis Type="Italic">p53</Emphasis>, <Emphasis Type="Italic">bax</Emphasis>, <Emphasis Type="Italic">bcl-2</Emphasis>, and <Emphasis Type="Italic">p21</Emphasis> expressed in colorectal cancer

Background We investigated the influence of genes on the apoptosis of colorectal tumor cells, based on DNA and mRNA kinetics.Methods In 30 colorectal cancer patients, we examined the mRNA expression of p53, bax, bcl-2, and p21 ^WAF1 , and we also investigated the development of tumor cell apoptosis, using a terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end labeling (TUNEL) method.Results TUNEL-positive cells showed a positive correlation with bax (P = 0.010) and a negative correlation with p21 (P = 0.04). We also investigated the relationship between p53 point mutation, p21 immunostaining degree, and apoptosis, based on DNA ladder expression. A remarkable correlation (P = 0.0090) was found between p21 and apoptosis.Conclusions The present study findings suggest that tumor cell apoptosis is (1) strongly inhibited by p21, (2) induced by bax, and (3) influenced by bcl-2, which, presumably, inhibits tumor cell apoptosis.     

<Emphasis Type="Italic">HER2</Emphasis> codon 655 polymorphism and breast cancer risk: a meta-analysis

To evaluate the association between HER2 codon 655 polymorphism and breast cancer risk in this meta-analysis. A comprehensive search was performed to identify all case–control studies investigating such association. Statistical analyses were conducted with software MIX 1.54. Twenty eligible reports, including 10,642 cases/11,259 controls, were identified. In overall analysis, the Val allele frequency in cases was significantly higher than that in controls (OR = 1.0921, 95% CI: 1.0013–1.191, P = 0.0466), while no associations were found in both recessive and dominant models. In subgroup analysis, HER2 codon 655 polymorphism was weakly associated with breast cancer risk in recessive (OR = 2.4624, 95% CI: 1.0619–5.7104, P = 0.0357), dominant (OR = 1.2781, 95% CI: 1.0353–1.5779, P = 0.0225), and co-dominant genetic models (OR = 1.2947, 95% CI: 1.0682–1.5693, P = 0.0085) in Asian population, respectively. Meanwhile, the susceptibility to breast cancer in people aged ≤45 was significantly increased in both recessive (OR = 2.2408; 95% CI: 1.2876–3.8998, P = 0.0043), and dominant models (OR = 1.2902, 95% CI: 1.1035–1.5085, P = 0.0014). No significant associations were observed in Caucasian, European, and Family history subgroups. So our analyses suggest HER2 codon 655 Val allele is weakly associated with an increased risk of breast cancer, and SNP at HER2 codon 655 could be considered as a susceptibility biomarker for breast cancer for Asian females or women age 45 years or younger. Weiyang Tao and Chunyang Wang contribute equally to this work.     

No association of <Emphasis Type="Italic">MDM2</Emphasis> SNP309 with risk of glioblastoma and prognosis

The MDM2 SNP309 variant has been shown to increase MDM2 expression and to be associated with tumor formation. In glioblastomas, the P53/MDM2 pathway is of crucial importance and MDM2 amplification is related to poor prognosis. However, we show here that MDM2 SNP309 is not associated with glioblastoma risk, and is not a prognostic factor.     

<Emphasis Type="Italic">ARLTS1</Emphasis> polymorphism is associated with an increased risk of familial cancer: evidence from a meta-analysis

Adenosine diphosphate (ADP)-ribosylation factor-like tumour suppressor gene 1(ARLTS1) might be associated with an increased risk of several types of familial cancers. However, previous studies have shown that cancer susceptibility is not completely consistent with ARLTS1 polymorphisms, and the precise mechanism remains unknown. Therefore, we conducted a meta-analysis of case-control studies by searching the PubMed, Embase, OVID, Science Direct and Chinese National Knowledge Infrastructure (CNKI) databases. In total, 12 studies met the inclusion criteria and were included in this meta-analysis. Statistical analyses were performed using STATA 11.0 software. Overall, the Cys148Arg T?>?C variant significantly increased cancer risk (CC vs. TT: OR?=?1.27, 95% CI?=?1.15–1.41, P?<?0.05). The stratification indicated that the Cys148Arg variant is significantly associated with sporadic cancer (CC vs. TT: OR?=?1.36, 95% CI?=?1.18–1.55) and familial cancer (CC vs. TT: OR?=?1.26, 95% CI?=?1.12–1.43). Trp149Stop, Pro131Leu, Ser99Ser and Leu132Leu were not correlated with cancer susceptibility. Based on these results, we demonstrated that the ARLTS1 Cys148Arg polymorphism is associated with an increased risk of sporadic cancer and familial cancer, and there were no associations between the other four SNPs (i.e., Trp149Stop, Pro131Leu, Ser99Ser and Leu132Leu) and cancer risk.     

<Emphasis Type="Italic">MDM2</Emphasis> SNP309 and <Emphasis Type="Italic">TP53</Emphasis> R72P associated with severe and febrile neutropenia in breast cancer patients treated with 5-FU/epirubicin/cyclophosphamide

The aim of this study was to investigate the association of two genetic polymorphisms, MDM2 SNP309 and TP53 R72P, with incidence of neutropenia in breast cancer patients treated with 5-FU/epirubicin/cyclophosphamide (FEC). Primary breast cancer patients (n = 216) treated with adjuvant FEC (60, 75 or 100 mg/m²) were included in this study. The association of genotypes of MDM2 SNP309 and TP53 R72P, determined by TaqMan SNP Genotyping Assays, with febrile neutropenia (FN) was investigated. In the patients treated with FEC100, G/G genotype for MDM2 SNP309 (G/G genotype ^MDM2 ) was significantly (P < 0.01) associated with a lower incidence (5.3 vs. 39.2%) of severe neutropenia (<100/mm³) than with T/T + T/G genotypes ^MDM2 , and C/C genotype for TP53 R72P (C/C genotype ^TP53 ) was significantly (P = 0.03) associated with a higher incidence (58.3 vs. 27.3%) of FN than with G/G + G/C genotypes ^TP53 . The combination of C/C genotype ^TP53 and T/T + T/G genotype ^MDM2 showed the highest risk for developing severe neutropenia (83.3%) and FN (62.5%) than any other combinations. In the patients treated with FEC60 or FEC75, there was no significant association of MDM2 SNP309 and TP53 R72P with severe neutropenia and FN. MDM2 SNP309 and TP53 R72P are significantly associated with severe neutropenia and FN, respectively, in breast cancer patients treated with FEC100, and especially their combination may be a useful predictor of severe neutropenia and FN.     

Relationship between <Emphasis Type="Italic">XRCC3</Emphasis> T241M polymorphism and gastric cancer risk: a meta-analysis

The X-ray repair complementing defective repair in Chinese hamster cells 3 (XRCC3) gene is a member of the RAD51 gene family. It encodes an important protein that functions in the homologous recombination repair of DNA double-strand break. In this study, our aim was to explore the relationship between XRCC3 T241M polymorphism and gastric cancer risk. Performing both the overall meta-analysis and subgroup meta-analysis based on ethnicity, source of controls, and cancer location with a total of 6 eligible studies (1,154 cases and 1,487 controls in all), we detected no significant gastric cancer risk variation for all genetic models in the overall analysis and in the subgroup analysis based on cancer location. What is interesting is in the subgroup analysis based on ethnicity, where significantly decreased gastric cancer risk was observed for recessive model in Asians (OR = 0.69, 95% CI = 0.50–0.95), while significantly increased gastric cancer risk was detected for dominant model in Caucasians (OR = 1.45, 95% CI = 1.01–2.08). In summary, according to the results of our meta-analysis, the XRCC3 T241M polymorphism might influence gastric cancer risk oppositely in Asians and Caucasians.     

Managing Patient with Mutations in <Emphasis Type="Italic">PALB2</Emphasis>, <Emphasis Type="Italic">CHEK2</Emphasis>, or <Emphasis Type="Italic">ATM</Emphasis>

Purpose of Review

The use of panel testing of multiple cancer-causing genes has allowed to find a subset of patients with harmful mutations in moderate penetrance genes. While extensive information is available regarding patients with BRCA1 and BRCA2 pathogenic variants, information regarding these less common genes and their management remains scarce. The aim of this review is to discuss penetrance, incidence, and management recommendations for PALB2, ATM, and CHEK2.

Recent Findings

NCCN guidelines now provide management recommendation for patients with pathogenic variants in these genes. In addition, more widespread testing has provided more information on penetrance and incidence. Although this is a huge step toward improving quality of care, prospective studies are still needed. We summarize the NCCN and other guidelines/suggestions for these genes and deliver our insight on the matter based on the best information we could find.

Summary

PALB2, ATM, and CHEK2 are less penetrant than BRCA1–2 and have a different spectrum, suggesting differing management. Data about incidence and penetrance along with management recommendations for these genes are provided.

     

Association of the <Emphasis Type="Italic">TCF7L2</Emphasis> polymorphism with colorectal cancer and adenoma risk

We evaluated the association of a polymorphism in TCF7L2 (RS12255372) in the WNT signaling pathway, which previously has been strongly associated with risk of Type II Diabetes, with colorectal cancer (CRC) and adenoma in the prospective Nurses’ Health Study (NHS) and Health Professionals Follow-up Study (HPFS) cohorts. Hyperinsulinemia may be related to the risk of colon adenoma and cancer, therefore this variant associated with reduced insulin secretion would be predicted to be inversely associated with colorectal cancer. Overall, in the NHS and HPFS, there was suggestive evidence for an inverse association associated with homozygosity for the minor allele of RS12255372 (TCF7L2 TT) and CRC (conditional and covariate adjusted OR = 0.63, 95% CI: 0.37–1.08; P for heterogeneity 0.52 for the association in women and men). In summary, the marginal association of the TCF7L2 SNP with CRC might be due to chance, but warrants further laboratory and epidemiological investigation.     

Genetic variation in <Emphasis Type="Italic">IGF1</Emphasis>, <Emphasis Type="Italic">IGFBP3</Emphasis>, <Emphasis Type="Italic">IRS1</Emphasis>, <Emphasis Type="Italic">IRS2</Emphasis> and risk of breast cancer in women living in Southwestern United States

Background An insulin-related pathway to breast cancer has been hypothesized. Methods We examine the 19 CA repeat of the IGF1 gene, the -202 C > A IGFBP3, the G972R IRS, and the G1057D IRS2 polymorphisms among 1,175 non-Hispanic white (NHW) and 576 Hispanic newly diagnosed breast cancer cases and 1,330 NHW and 727 Hispanic controls living in Arizona, Colorado, New Mexico, and Utah. Results Among post-menopausal women not recently exposed to hormones, not having the 19 CA repeat of IGF1 gene was associated with breast cancer among NHW women [odds ratio (OR) 2.14, 95% confidence interval (CI) 1.21–3.79] and having an R allele of G972R IRS1 increased breast cancer risk among Hispanic women (OR 2.70, 95% CI 1.13–6.46). Among post-menopausal Hispanic women recently exposed to hormones the A allele of the -202 C > A IGFBP3 polymorphism increased risk of breast cancer (OR 1.57, 95% CI 1.06–2.33). The IGF1 19 CA repeat polymorphism interacted with hormone replacement therapy (HRT) among NHW post-menopausal women; women who had the 19/19 IGF1 genotype were at reduced risk of breast cancer (OR 0.64, 95% CI 0.47–0.88) if they did not use HRT. We also observed interaction between body mass index and IGF1 19 CA repeat (p=0.06) and between weight gain and the -202 C > A IGFBP3 polymorphism (p=0.05) in NHW post-menopausal women not recently exposed to hormones. Conclusions Our data suggest that associations between insulin-related genes and breast cancer risk among women living in the Southwestern United States may be dependent on estrogen exposure and may differ by ethnicity.     

<Emphasis Type="Italic">MTRR A66G</Emphasis> polymorphism and breast cancer risk: a meta-analysis

Methionine synthase reductase (MTRR) is one of the important enzymes involved in the folate metabolic pathway and its functional genetic polymorphisms may be associated with breast cancer risk. However, this relationship remains inconclusive. For better understanding the effect of MTRR A66G polymorphism on breast cancer risk, a meta-analysis was performed. By searching PubMed and EMBASE, a total of six case–control studies, containing 6,084 cases and 6,756 controls, were included. The strength of association between MTRR A66G polymorphism and breast cancer risk was assessed by odds ratio (OR) with the corresponding 95% confidence interval (95% CI). The results strongly suggested that there was no significant association between MTRR A66G polymorphism and breast cancer susceptibility in overall comparisons in all genetic models (additive model: OR 1.00, 95% CI 0.89–1.11, P = 0.943; dominant model: OR 1.00, 95% CI 0.91–1.10, P = 0.989; recessive model: OR 1.00, 95% CI 0.91–1.09, P = 0.926). Similarly, in subgroup analyses for ethnicity (Caucasian, Asian and mixed population) and folate intake status (high and low folate intake), the results were negative. Sensitivity analysis demonstrated that omitting any study did not perturb the results. In conclusion, this meta-analysis strongly suggests that MTRR A66G polymorphism is not associated with breast cancer risk, especially in Caucasians and Asians.     

Polymorphisms in three obesity-related genes (<Emphasis Type="Italic">LEP</Emphasis>, <Emphasis Type="Italic">LEPR</Emphasis>, and <Emphasis Type="Italic">PON1</Emphasis>) and breast cancer risk: a meta-analysis

Common genetic variations in the leptin (LEP), leptin receptor (LEPR), and paraoxonase 1 (PON1) genes have been considered to be implicated in the development of breast cancer. However, the results were inconsistent. In this study, a meta-analysis was performed to assess the associations of five polymorphisms, including LEP G2548A, LEPR Q223R, LEPR Lys109Arg, PON1 L55M, and PON1 Q192R polymorphisms, with breast cancer risk. Published literature from PubMed, ISI Web of Science, Embase databases, CNKI, and Wanfang Data were retrieved. All studies evaluating the association between LEP G2548A, LEPR Q223R, LEPR Lys109Arg, PON1 L55M, or PON1 Q192R polymorphism and breast cancer risk were included. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. Three studies (2,003 cases and 1,967 controls) for LEP G2548A polymorphism, nine studies (4,627 cases and 5,476 controls) for LEPR Q223R polymorphism, five studies (2,759 cases and 2,573 controls) for LEPR Lys109Arg polymorphism, four studies (1,517 cases and 1,379 controls) for PON1 L55M polymorphism, and five studies (1,575 cases and 2,283 controls) for PON1 Q192R polymorphism were included in the meta-analysis. Overall, the results showed null significant association between LEP G2548A, LEPR Q223R, LEPR Lys109Arg, or PON1 Q192R polymorphism and breast cancer risk; however, PON1 L55M was significantly associated with breast cancer risk overall (MM vs. LL: OR = 2.16; 95% CI, 1.76–2.66). For LEPR Q223R polymorphism, further subgroup analysis suggested that the association was only statistically significant in East Asians (OR = 0.50; 95% CI, 0.36–0.70) but not in Caucasians (OR = 1.06; 95% CI, 0.77–1.45) or Africans (OR = 1.30; 95% CI, 0.83–2.03). The present meta-analysis suggested that LEPR Q223R polymorphism might be implicated in the development of breast cancer in East Asians; PON1 L55M might increase breast cancer risk. However, given the limited sample size, the findings warrant further investigation.     

Genetic polymorphisms of <Emphasis Type="Italic">MDM2</Emphasis> and <Emphasis Type="Italic">TP53</Emphasis> genes are associated with risk of nasopharyngeal carcinoma in a Chinese population

Background  

The tumor suppressor TP53 and its negative regulator MDM2 play crucial roles in carcinogenesis. Previous case-control studies also revealed TP53 72Arg>Pro and MDM2 309T>G polymorphisms contribute to the risk of common cancers. However, the relationship between these two functional polymorphisms and nasopharyngeal carcinoma (NPC) susceptibility has not been explored.     

<Emphasis Type="Italic">TP53</Emphasis> Arg72Pro polymorphism and endometrial cancer risk: a meta-analysis

Studies investigating the relationship between TP53 Arg72Pro polymorphism and endometrial cancer risk reported conflicting results. To explore a more precise estimate of the effect of this polymorphism on endometrial carcinogenesis, a meta-analysis was performed by searching eligible studies in PubMed. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association for codominant model (Arg/Arg vs. Pro/Pro, Arg/Pro vs. Pro/Pro), dominant model (Arg/Arg + Arg/Pro vs. Pro/Pro), and recessive model (Arg/Arg vs. Arg/Pro + Pro/Pro), respectively. Subgroup analyses were performed by Hardy–Weinberg equilibrium (HWE) in controls, the specimen of cases for determining TP53 genotypes, sample size, the source of control and case groups, and ethnicity. We identified 8 case–control studies involving 2,154 subjects for this meta-analysis. Overall, no evidence of association was observed between TP53 genotypes and endometrial cancer risk in all genetic models (Arg/Arg vs. Pro/Pro: OR = 0.98, 95% CI: 0.69–1.39, P = 0.90; Arg/Pro vs. Pro/Pro: OR = 1.00, 95% CI: 0.71–1.42, P = 0.98; dominant model: OR = 0.99, 95% CI: 0.71–1.38, P = 0.95; recessive model: OR = 1.06, 95% CI: 0.80–1.41, P = 0.95). Stratified analyses also detected no significant association in any subgroup, except among those studies with controls deviated from HWE in recessive model (OR = 1.60, 95% CI: 1.07–2.39). In conclusion, we did not observe any evidence for a role of TP53 Arg72Pro polymorphism in endometrial cancer. The reported significant association between this polymorphism and endometrial cancer risk may be due to methodological errors such as selection bias, small sample size, Type I error, and population stratification.     

<Emphasis Type="Italic">PALB2</Emphasis> analysis in <Emphasis Type="Italic">BRCA2</Emphasis>-like families

BRCA2 and PALB2 function together in the Fanconi anemia (FA)–Breast Cancer (BRCA) pathway. Mono-allelic and bi-allelic BRCA2 and PALB2 mutation carriers share many clinical characteristics. Mono-allelic germline mutations of BRCA2 and PALB2 are risk alleles of female breast cancer and have also been reported in familial pancreatic cancer, and bi-allelic mutations cause a severe form of Fanconi anemia. In view of these similarities, we investigated whether the prevalence of PALB2 mutations was increased in breast cancer families with the occurrence of BRCA2 associated tumours other than female breast cancer. PALB2 mutation analysis was performed in 110 non-BRCA1/2 cancer patients: (a) 53 ovarian cancer patients from female breast-and/or ovarian cancer families; (b) 45 breast cancer patients with a first or second degree relative with pancreatic cancer; and (c) 12 male breast cancer patients from female breast cancer families. One truncating PALB2 mutation, c.509_510delGA, resulting in p.Arg170X, was found in a male breast cancer patient. We conclude that germline mutations of PALB2 do not significantly contribute to cancer risk in non-BRCA1/2 cancer families with at least one patient with ovarian cancer, male breast cancer, and/or pancreatic cancer.     

Variation in breast cancer risk in <Emphasis Type="Italic">BRCA1</Emphasis> and <Emphasis Type="Italic">BRCA2</Emphasis> mutation carriers

Genetic testing for BRCA1 and BRCA2 (BRCA1/2) mutations can provide important information for women who are concerned about their breast and ovarian cancer risks and need to make relevant prevention and medical management decisions. However, lifetime risks of breast cancer in individual BRCA1/2 mutation carriers have been confusing to apply in clinical decision-making. Published risk estimates vary significantly and are very dependent on the characteristics of the population under study. Recently, Begg and colleagues estimated cancer risks in a population-based study of BRCA1/2 mutation carriers. Here, we discuss the clinical decision-making implications of this research in the context of risk factors that may influence risk estimates in BRCA1/2 mutation carriers.     

The role of <Emphasis Type="Italic">LINE</Emphasis>-<Emphasis Type="Italic">1</Emphasis> methylation in predicting survival among colorectal cancer patients: a meta-analysis

Background

The prognostic value of long interspersed nucleotide element-1 (LINE-1) methylation in patients with colorectal cancer (CRC) remains uncertain. We have therefore performed a meta-analysis to elucidate this issue.

Methods

The PubMed and Web of Science databases were searched for studies published up to 30 June 2016 which reported on an association between LINE-1 methylation and overall survival (OS), disease-free survival (DFS), or cancer-specific survival (CSS) among CRC patients. The reference lists of the identified studies were also analyzed to identify additional eligible studies. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using the fixed-effects or the random-effects model. Stratification analysis and meta-regression analysis were performed to detect the source of heterogeneity. Analyses of sensitivity and publication bias were also carried out.

Results

Thirteen independent studies involving 3620 CRC patients were recruited to the meta-analysis. LINE-1 hypomethylation was found to be significantly associated with shorter OS (HR 2.92, 95% CI 2.20–3.88, p < 0.001) and DFS (HR 2.18, 95% CI 1.46–3.27, p < 0.001), as well as unfavorable CSS (HR 1.96, 95% CI 1.35–2.85, p < 0.001). No heterogeneity was found among the studies evaluating the associations between LINE-1 hypomethylation and OS or DFS, with the exception being CSS. Moreover, meta-regression analysis suggested that one of the contributors to between-study heterogeneity on the association between LINE-1 methylation and CSS was statistical methodology. The subgroup analysis suggested that the association in studies using the Cox model statistical method (HR 2.76, 95% CI 1.90–4.01, p < 0.001) was stronger than that in studies using the Log-rank test (HR 1.41, 95% CI 1.07–1.87, p = 0.015).

Conclusions

The results of this meta-analysis suggest that LINE-1 methylation is significantly associated with the survival of CRC patients and that it could be a predictive factor for CRC prognosis.

     

A <Emphasis Type="Italic">CYP19</Emphasis> (aromatase) polymorphism is associated with increased premenopausal breast cancer risk

Due to the established association between estrogen levels and breast cancer risk, polymorphic variation in genes regulating estrogen levels is thought to be related to breast cancer risk. Aromatase, the protein product of the CYP19 gene, is involved in the production of endogenous estrogens via androgen conversion. We examined whether polymorphic variation in CYP19 associated with increased breast cancer risk in a population based case-control study. We examined two single nucleotide polymorphisms (SNP), rs1008805 (A/G) and rs730154 (C/T), which have been shown to tag SNPs within two different haplotype blocks in CYP19. Among premenopausal women, the presence of at least one G allele at rs1008805 was significantly associated with an increase in the risk of breast cancer (OR = 1.72 [95% CI, 1.20–2.49]), especially with estrogen and progesterone receptor negative breast cancer (OR = 3.89 [1.74–8.70] and OR = 2.52 [1.26–5.05], respectively). No association was observed among postmenopausal women (OR = 1.06 [0.82–1.36]). There was no significant association between rs730154 and breast cancer, regardless of menopausal status. Our results suggest that premenopausal women carrying the G allele at CYP19 rs1008805 have increased risk of breast cancer. The finding supports the potential role of variation in estrogen biosynthesis genes in premenopausal breast cancer risk.     

<Emphasis Type="Italic">CCND1</Emphasis> G870A polymorphism contributes to breast cancer susceptibility: a meta-analysis

Cyclin D1 (CCND1), a key cell cycle regulatory protein that governs the cell cycle progression from G1 to S phase, can promote cell proliferation or induce growth arrest and apoptosis. Since the identification of a well-characterized functional polymorphism, G870A in exon 4 of CCND1, several molecular epidemiological studies were conducted in recent years to evaluate the association between G870A and breast cancer risk in diverse populations. However, the results remain conflicting rather than conclusive. This meta-analysis on 5,371 cases with breast cancer and 5,336 controls from 7 published case-control studies showed that the variant allele 870A was associated with a significantly increased risk of breast cancer (AA vs. GG: OR = 1.18, 95% CI = 1.06–1.32; AG vs. GG: OR = 1.12, 95% CI = 1.01–1.23; AA/AG vs. GG: OR = 1.14, 95% CI = 1.04–1.25) without any between-study heterogeneity. In the stratified analysis by race, we found that the increased breast cancer risk associated with G870A polymorphism was more evident in Caucasians (OR = 1.14, 95% CI = 1.01–1.28, P = 0.88 for heterogeneity test), but not significant in Asians (OR = 1.10, 95% CI = 0.85–1.42, P = 0.05 for heterogeneity test). The results suggest that CCND1 G870A polymorphism may contribute to breast cancer development, especially in Caucasians. Additional well-designed large studies were required for the validation of this association in different populations. Cheng Lu and Jing Dong contributed equally to this work.