Genetic polymorphisms of metastasis suppressor gene NME1 and breast cancer survival

PURPOSE: Ample evidence supports an important role of tumor metastasis suppressor genes in cancer metastatic processes. We evaluated the association of genetic polymorphisms of metastasis suppressor gene NME1 with breast cancer prognosis in a follow-up study of patients with primary breast cancer and further investigated the functions of these polymorphisms. EXPERIMENTAL DESIGN: NME1 genotypes were analyzed in a cohort of 1,134 breast cancer patients recruited as part of the Shanghai Breast Cancer Study who were followed for a median of 7.1 years. In vitro biochemical analyses were carried out to examine the function of NME1 gene polymorphisms. RESULTS: Single nucleotide polymorphisms (SNP) in the promoter region of the NME1 gene were found to be associated with breast cancer prognosis. Patients carrying the C allele in rs16949649 were associated with higher breast cancer-specific mortality [hazard ratio (HR), 1.4; 95% confidence interval (95% CI), 1.1-1.9] compared with those carrying the wild-type allele, and the association was more evident in patients with an early-stage cancer (HR, 1.7; 95% CI, 1.2-2.5). SNP rs2302254 was also associated with breast cancer prognosis, and the association was statistically significant for the risk of breast cancer relapse, metastasis, and death (HR, 1.3; 95% CI, 1.0-1.6). In vitro biochemical analyses showed that minor alleles in rs2302254 and rs3760468, which is in strong linkage disequilibrium with rs16949646, altered nuclear proteins binding capacity and reduced NME1 promoter activity, supporting the results from an association study of these SNPs with breast cancer survival. CONCLUSION: Promoter polymorphisms in the NME1 gene may alter its expression and influence breast cancer survival.     

新疆ABCG2基因多态性与乳腺癌复发的相关性研究

背景与目的:复发转移是影响乳腺癌患者生存预后的关键因素,其涉及的病理学机制复杂,临床上尚未开发出早期监测的生物学标志物。探讨三磷酸腺苷结合盒家族G2(adenosine triphosphate-binding cassette family G2,ABCG2)基因多态性与新疆地区乳腺癌患者辅助化疗2年后复发的相关性,分析其作为乳腺癌复发标志物的可能性。方法:收集2014年12月-2015年12月于新疆医科大学第三临床医学院接受手术治疗后2年内复发的乳腺癌患者150例,同期收集手术后2年内未出现复发的患者162例作为对照。收集临床资料,并检测rs2032582、rs1045642、rs2231137和rs2231142位点的多态性,比较4个位点与乳腺癌2年内复发的相关性。结果:两组患者在年龄、淋巴结转移个数、雌激素受体(estrogen receptor,ER)(+)、孕激素受体(progesterone receptor,PR)(+)、组织学分级中存在差异;rs2032582在两组之间表达存在差异,rs2032582 GG型在复发组中表达显著高于其他突变类型(P<0.05)。2年复发组中rs2032582位点G/T等位基因组的年龄显著高于A等位基因组(P<0.01),而A等位基因组的肿块大小、淋巴结转移个数和ER(+)显著高于G/T等位基因组(P<0.05)。结论:rs2032582位点可能与乳腺癌治疗2年后复发相关,rs2032582 GG基因型是乳腺癌复发的危险因素,ABCG2可作为早期监测乳腺癌复发的标志基因。     

XRCC1和XRCC2的基因多态性在乳腺癌治疗中的临床意义

目的:乳腺癌是女性常见的恶性肿瘤之一,其发生发展与遗传因素十分密切,寻找与乳腺癌发生、病理、治疗及预后相关的分子标志物对于该病的治疗具有重要的指导意义。XRCC是参与DNA损伤修复的重要基因。XRCC1及XRCC2基因的多态性已被研究与多种肿瘤易感性及生物学行为有关。本实验研究XRCC1 和XRCC2 多态性与中国女性乳腺癌发病风险、临床病理（腋窝淋巴结转移状态）及预后(复发和转移)的相关性,以探讨其在乳腺癌临床治疗中的潜在价值。方法:采用PCR-RFLP方法检测60例原发性乳腺癌患者新鲜血标本中XRCC1 Arg399Gln、XRCC2 C41657T、XRCC2 G4234C多态,采用SAS 9.1.3统计软件分析基因型与乳腺癌发病风险、临床病理及预后的相关性。结果:XRCC1 Arg399Gln 不同基因型与乳腺癌的发病风险不存在统计学相关性(P>0.05); XRCC1 Arg399Gln与乳腺癌的腋窝淋巴结转移情况及乳腺癌的远处转移、局部复发不存在相关性(P>0.05);XRCC2 C41657T、XRCC2 G4234C 基因型与乳腺癌的发病风险均无显著相关(P>0.05);XRCC2 C41657T C/T和T/T基因型的多态性可能与乳腺癌的腋窝淋巴结转移状态、乳腺癌的远处转移及局部复发具有相关性(P<0.05)。结论:XRCC1 Arg399Gln G/G、XRCC2 C41657T、XRCC2 G4234C 基因型可能均与乳腺癌的发病风险无关。XRCC2 C41657T C/T和T/T基因型的多态性可能与乳腺癌的腋窝淋巴结转移状态、乳腺癌的远处转移及局部复发具有相关性。     

132例三阴性乳腺癌患者的临床特征与预后分析

目的探讨三阴性乳腺癌的临床特征及影响预后的因素。方法采用回顾性方法对我院132例三阴性乳腺癌患者的临床特征进行分析,并根据随访资料分析了患者的生存情况及预后因素。所有患者均经免疫组化证实ER、PR、Her-2为阴性。结果132例三阴性乳腺癌患者占同期乳腺癌患者（774例）的17．1％,绝经前患者（91例）占68．9％,53．8％的患者（71例）发病时肿块大小为T2,39．4％患者（52例）腋窝淋巴结阳性。中位随访时间63个月,共有33例出现复发或转移,其中20例死亡,23例同时出现2个部位以上的转移,5年的无病生存率为73．8％,总生存率为85．7％。淋巴结阳性患者复发转移风险较淋巴结阴性患者明显增加（P=0．001）。结论三阴性乳腺癌患者大多在治疗后2—3年发生多发转移,仅淋巴结状况是影响其预后的重要因素,淋巴结阳性的三阴性乳腺癌患者预后差。     

Promoter polymorphisms in matrix metalloproteinases and their inhibitors: few associations with breast cancer susceptibility and progression

The importance of matrix metalloproteinases and their inhibitors in tumor progression is well documented. We wanted to investigate if single nucleotide polymorphisms (SNPs) in the promoter regions of these genes are associated with susceptibility to or progression of breast cancer. In this, so far largest case–control study, we genotyped eight SNPs in the MMP1, MMP2, MMP3, MMP9, MMP13, RECK and TIMP3 genes in a well-characterized breast cancer series of 959 cases and 952 controls from Sweden. Even though we did not correct for multiple comparisons, only a few associations were noted. We observed a moderately increased risk for the TT homozygotes of the MMP9−1562 C/T SNP (OR 1.88, 95% CI 0.97–3.63) and for the C allele carriers of the TIMP3−1296 T/C SNP (OR 1.25, 95% CI 1.05–1.50). In the survival analysis, only the TC heterozygotes of the RECK−420 T/C SNP showed a better survival compared to the TT homozygotes (P = 0.02 in all cases and P = 0.03 in lymph node negative cases). None of the other SNPs conferred an increased breast cancer risk, nor did they correlate with survival. A combination of the −585 TT homozygosity in the RECK gene and the −1296 TT homozygosity in the TIMP3 gene correlated with estrogen and progesterone receptor status (OR 1.81, 95% CI 1.03–3.21 and OR 2.10, 95% CI 1.18–3.86, respectively), and a combination of the −1306 TT homozygosity in the MMP2 gene and the −1562 CC homozygosity in the MMP9 gene with progesterone receptor status (OR 2.34, 95% CI 1.08–5.08). Although our study suggests some correlations between the studied SNPs and the progression of breast cancer, the rarity of the risk genotypes limits their usefulness in the clinic. Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.     

Treatment results and prognostic factors of early breast cancer treated with a breast conserving operation and radiotherapy

BACKGROUND: The purpose of this study was to analyze the prognostic factors affecting local control and survival rates for patients with early breast cancer who received breast conserving treatment (BCT) and to find out the optimal treatment according to their risk factors. METHODS: From October 1994 to December 2001, 605 patients with 611 stage I and II breast cancers received BCT, and the results were analyzed retrospectively. BCT consists of breast conserving surgery and whole breast irradiation. All the patients underwent lumpectomy or quadrantectomy. Axillary lymph node dissection or sentinel lymph node biopsy was performed in 608 cases (99.5%). The radiation dose to the whole breast was 50.4 Gy over 5 weeks with a 1.8 Gy daily fraction and with boost doses of 9-14.4 Gy administered to the tumor bed. Adjuvant chemotherapy was performed in most of the patients with axillary lymph node metastasis or tumors larger than 1 cm. The median follow-up period was 47 months. RESULTS: Local relapse, regional relapse and distant metastasis occurred in 15 (2.5%), 16 (2.6%) and 43 patients (7.1%), respectively. The 5-year overall survival, local-relapse-free survival, distant-metastasis-free survival and disease-free survival rates were 95.3%, 97.2%, 91.3% and 88.5%, respectively. On multivariate analysis, age (P = 0.02), number of involved axillary lymph nodes (P = 0.01) and nuclear grade (P = 0.01) affected the local-relapse-free survival. The factors associated with disease-free survival were the T stage (P = 0.05), number of involved axillary lymph nodes (P = 0.01) and nuclear grade (P = 0.001). Overall survival was associated with the T stage (P = 0.02), number of involved axillary lymph nodes (P = 0.01) and c-erb B2 overexpression (P = 0.05). Patients with more than two factors among (i) age 1 cm, (ii) positive lymph node metastasis and (iii) high nuclear grade showed an inferior 5-year disease-free survival rate compared with others (P = 0.0005). CONCLUSIONS: The most important prognostic factor affecting local control, disease-free survival and overall survival was axillary lymph node metastasis. The nuclear grade influenced local control and disease relapse. Patients with multiple unfavorable risk factors such as positive axillary lymph nodes, high nuclear grade, young age and large tumor showed poorer local control and disease-free survival than patients without any risk factors, and so more aggressive treatment is required for these patients.     

乳腺癌基因分型与患者临床病理及预后的关系

目的 探讨乳腺癌基因分型与患者临床病理信息及预后特征的相关性。方法 在ArrayExpress数据库中下载乳腺癌的芯片数据,利用affy程序和YuGene程序将芯片数据进行整合,得到AE-meta乳腺癌数据集。下载癌症基因组图谱（TCGA）中乳腺癌RNA测序数据,得到TCGA乳腺癌数据集。利用AIMS程序进行乳腺癌基因分型,比较两个数据集中基因分型和患者临床病理信息及预后特征的相关性。结果 两数据集的临床病理信息相关性分析显示,LumA型多发于年长女性,肿瘤体积较小,分化较好,淋巴结侵犯转移也较少;Basal型好发于年轻女性,肿瘤体积较大,分化较差,淋巴结侵犯转移却较少;HER2型的恶性程度较高,淋巴结侵犯转移较多,但无特定发病年龄趋势。预后特征分析显示,LumA型患者生存预后最好、复发转移最少,HER2和Basal型患者生存预后最差、复发转移最多,LumB和NorL型死亡和复发风险处于中间。在骨转移及肺转移中,各基因亚型均有较高转移风险;在脑转移中,Basal型的风险最高;在肝转移中,Basal和HER2型的风险最高。结论 乳腺癌基因分型能较好反映患者临床病理和预后特征,具有较好的临床指导价值。     

术后放疗对T1-T2期乳腺癌患者预后的影响

目的:探讨术后放疗对T1-T2期伴有1～3个腋淋巴结转移、腋窝淋巴结清除相对彻底的乳腺癌患者的疗效及其对预后的影响。方法:选择2009年8月1日-2012年1月15日上海交通大学附属第六人民医院收治的185例T1-T2期伴有1～3个腋淋巴结转移的乳腺癌患者为研究对象,分为研究组(n＝93)和对照组(n＝92)。对照组行乳腺癌改良根治术以及腋窝淋巴结清除术,研究组在此基础上行放疗。观察两组患者1、2、3年总生存率、无病生存率,并分析影响预后的独立危险因素。结果:研究组1、2、3年总生存率分别为97.83%、96.74%、89.13%,与对照组相比,差异无统计学意义(P＝0.235 6,P＝0.181 2,P＝0.128 1);研究组1、2、3年无病生存率分别为94.57%、92.39%、89.13%,显著高于对照组(P＝0.041 8,P＝0.039 0,P＝0.039 0);单因素分析表明患者术后无病生存率可能与肿瘤分期、腋窝淋巴结转移数、PR、放疗与否有关,而与患者年龄、ER、月经状态无关,进一步Cox回归分析显示腋窝淋巴结转移数(P＝0.046)、放疗与否(P＝0.012)是影响无病生存率的独立预后因素。结论:术后放疗可提高T1-T2期伴有1～3个腋淋巴结转移的乳腺癌患者无病生存率,腋窝淋巴结转移以及放疗与否是影响患者预后的独立危险因素。     

Genome-Wide Association Studies (GWAS) breast cancer susceptibility loci in Arabs: susceptibility and prognostic implications in Tunisians

Genome-wide Association Studies (GWAS) revealed novel genetic markers for breast cancer susceptibility. But little is known about the risk factors and molecular events associated with breast cancer in Arab Population. Therefore, we designed a broad study to investigate the susceptibility and prognostic implications of the GWAS breast cancer loci in the Tunisian population. In a cohort of 640 unrelated patients with breast cancer and 371 healthy control subjects, we characterized the variation of 9 single nucleotide polymorphisms (SNPs), namely rs1219648, rs2981582; rs8051542, rs12443621, and rs3803662; rs889312; rs3817198; rs13387042 and rs13281615. Only 5 out of 9 GWAS breast cancer loci were found to be significantly associated with breast cancer in Tunisians: The rs1219648 (G vs. A allele: OR?=?1.36, P?=?1?×?10(-3)) and rs2981582 (A vs. G allele: OR?=?1.55, P?=?3?×?10(-6)) of FGFR2 gene; the rs8051542 of the TNRC9 gene (T vs. C allele: OR?=?1.40, P?=?4?×?10(-4)); the rs889312 of the MAP3K1 gene (C vs. A allele: OR?=?1.33, P?=?3?×?10(-3)) and the rs13281615 located on 8q24 (G vs. A allele: OR?=?1.21, P?=?0.03). Homozygous variant genotypes of rs2981582 were strongly related to lymph node negative breast cancer (OR?=?3.33, P?=?6?×?10(-7)) and the minor allele of rs2981582 was associated with increased risk of ER+ tumors (OR?=?1.57, P?=?0.02; OR?=?2.15, P?=?0.001, for heterozygous and homozygous variant genotypes, respectively) and increased risk of distant metastasis development (OR?=?2.30, P?=?4?×?10(-3); OR?=?3.57, P?=?6?×?10(-5), for heterozygous and homozygous variant genotypes, respectively) in a dose dependent manner. The association for rs8051542 was stronger for high-grade SBR tumors (OR?=?2.54, P?=?2?×?10(-4)). GG genotype of rs13387042 on 2q35 showed a significant association with the risk of developing distant metastasis (OR?=?1.94, P?=?0.02). The G allele of rs1219648 in FGFR2 and the A allele of rs13387042 on 2q35 indicated a better prognosis by showing a significantly higher overall survival rates (P?=?0.013 and P?=?0.005, respectively). In conclusion, GWAS breast cancer FGFR2, TNRC9, MAP3K1, and 8q24 loci are associated with an increased risk of breast cancer and genetic variation in FGFR2 gene may predict the aggressiveness of breast cancer in Tunisians.     

The MMP-2 -735 C Allele is a Risk Factor for Susceptibility to Breast Cancer

Background: The expression of MMP genes has been demonstrated to be associated with tumor invasion, metastasis and survival rate for a variety of cancers. The functional promoter polymorphism MMP-2 C-735T is associated with decreased expression of the MMP-2 gene. The aim of present study was to detect any association between MMP-2 C-735T and susceptibility to breast cancer. Materials and Methods: The MMP-2 C-735T polymorphism was studied in 233 women (98 with breast cancer and 135 healthy controls). All studied women were from Kermanshah and Ilam provinces of Western Iran. The MMP-2 C-735T polymorphism was detected using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: The frequencies of MMP-2 CC, CT and TT genotypes in healthy individuals were 59.3, 38.5 and 2.2%, respectively. However, in breast cancer patients, only CC (71.4%) and CT (28.6%) genotypes were observed (p=0.077). In patients the frequency of the MMP-2 C allele was significantly higher (85.7%) compared to that in controls (78.5 %, p=0.048). The presence of C allele of MMP-2 increased the risk of breast cancer by 1.64-fold [OR=1.64 (95%CI 1.01-2.7, p=0.049)]. The frequency of MMP-2 C allele was also higher in patients ≤40 years (88.9%) than those aged ≥41 years (67.5%, p=0.07). In addition, the frequency of MMP-2 C allele tended to be higher in patients with a family history of cancer in first –degree relatives (76.6%) compared to that without a family history of cancer (67.3%, p=0.31). Conclusions: Our findings indicate that the C allele of MMP-2 C-735T polymorphism is associated with increased risk of breast cancer. Also, the MMP-2 C allele might increase the risk of young onset breast cancer in our population.     

乳腺癌组织MMP-2、MMP-9和TIMP-2蛋白表达与肿瘤的转移及预后

目的　探讨乳腺癌组织中基质金属蛋白酶 (MatrixMeralloproteinases,MMPS)和金属蛋白酶组织抑制物 (TissueInhibitorsofMeralloproteinases,TIMPS)基因表达与肿瘤发生、病理分级、转移及预后之间的关系。方法　采用免疫组化LSAB法对 5 0例具有完整临床资料的乳腺癌组织及 2 0例乳腺纤维腺瘤的组织标本分别进行MMP 2、MMP 9和TIMP 2标记检测。结果　 5 0例乳腺癌组织中MMP 2、MMP 9和TIMP 2的表达分别为 74 % (37/ 5 0 )、6 5 % (31/ 5 0 )和 5 6 % (2 8/ 5 0 ) ,而在癌旁组织及良性纤维腺瘤增生的导管上皮中大部分不着色 ,少部分有微弱的着色 ,三者的表达与肿瘤的发生明显相关 ;MMP 2的高表达与肿瘤的病理分级、淋巴结的转移及临床预后复发均呈明显的正相关 (P <0 .0 5 ) ,TIMP 2的高表达与病理分级 ,淋巴结转移及预后复发呈明显的负相关 (P <0 .0 5 ) ,但MMP 9的表达却与临床因素无明显相关性。结论　乳腺癌组织中MMP 2高表达预示着病人预后更差 ,比MMP 9对乳癌患者转移及预后更具有判断价值 ,评价MMP 2和TIMP 2之间的平衡有利于早期了解预后 ,且比单独采用MMP 2指标更有利于了解癌肿的进展及预后。     

Protein arginine methyltransferase 7 promotes breast cancer cell invasion through the induction of MMP9 expression

Recent evidence points to the protein arginine methyltransferase (PRMT) family of enzymes playing critical roles in cancer. PRMT7 has been identified in several gene expression studies to be associated with increased metastasis and decreased survival in breast cancer patients. However, this has not been extensively studied. Here we report that PRMT7 expression is significantly upregulated in both primary breast tumour tissues and in breast cancer lymph node metastases. We have demonstrated that reducing PRMT7 levels in invasive breast cancer cells using RNA interference significantly decreased cell invasion in vitro and metastasis in vivo. Conversely, overexpression of PRMT7 in non-aggressive MCF7 cells enhanced their invasiveness. Furthermore, we show that PRMT7 induces the expression of matrix metalloproteinase 9 (MMP9), a well-known mediator of breast cancer metastasis. Importantly, we significantly rescued invasion of aggressive breast cancer cells depleted of PRMT7 by the exogenous expression of MMP9. Our results demonstrate that upregulation of PRMT7 in breast cancer may have a significant role in promoting cell invasion through the regulation of MMP9. This identifies PRMT7 as a novel and potentially significant biomarker and therapeutic target for breast cancer.     

乳腺癌淋巴管生成与淋巴结转移、血管内皮生长因子-C表达的关系

目的 探讨乳腺癌中淋巴管生成的分布特点及与血管内皮生长因子-C(VEGF-C)的表达,淋巴结转移和预后的关系.方法 应用免疫组化方法检测70例乳腺癌组织VEGF-C蛋白的表达,并用淋巴管内皮细胞特异性抗体D2-40标记淋巴管,计数肿瘤淋巴管密度(LVD),结合临床病理特征和随访资料进行分析.结果 VEGF-C蛋白的高表达与淋巴结转移(P=0.010)、淋巴管浸润(P=0.031)呈正相关,与肿瘤组织学分级 (P＜0.001) 呈负相关.乳腺癌LVD与淋巴结转移(P＜0.001)、淋巴管浸润(LVI)(P=0.001)、VEGF-C表达(P=0.012)呈正相关,与无病生存率(P=0.011)及总生存率(P=0.001)呈显著负相关.多因素分析显示LVD是影响无病生存率(P=0.015)和总生存率(P=0.002)的独立因子.结论 乳腺癌组织中新生淋巴管主要分布于肿瘤间质,LVD与VEGF-C表达和癌细胞转移相关,乳腺癌微淋巴管密度测定对评估其淋巴结转移和预后判断可能具有意义.     

MMP-3在乳腺导管癌中的表达及临床意义

目的：检测MMP-3在乳腺导管癌中的表达,探讨其临床意义及与乳腺导管癌临床病理参数的关系。方法：应用免疫组化MaxVision法检测48例乳腺导管癌患者MMP-3的表达,分析MMP-3与乳腺导管癌患者的年龄、肿瘤大小、组织学类型、淋巴结转移及肿瘤ER、PR、E-cad、C—erbB-2的关系。结果：MMP-3在乳腺导管癌组织中的阳性表达显著高于乳腺正常组织（P〈0．05）。MMP-3在无淋巴结转移和C—erb—B阳性的乳腺导管癌组织的阳性表达率显著高于相应对照组（P〈0．05）;而在不同年龄、肿瘤大小、组织学类型及肿瘤ER、PR、E—cad、C—erbB-2分组问的表达无显著差异（P〉0．05）。结论：MMP-3在无淋巴结转移的乳腺导管癌组织高表达,和较早阶段乳腺导管癌的发生发展密切相关,将有可能预测高危人群作出早期诊断;MMP-3在C—erbB-2阳性的乳腺导管癌组织显著高表达,联合检测这两个指标对判断乳腺导管癌的预后可能有重要意义。     

nm23基因在乳腺癌中的表达及与远处转移相关性的研究

应用免疫组化方法，对１０１例有８年随访结果的乳腺癌病例，进行了ｎｍ２３基因蛋白表达的检测。结果显示，ｎｍ２３基因蛋白表达与血行转移、淋巴结转移的发生呈负相关，与其它临床指标无关。生存率分析表明：ｎｍ２３基因高表达组患者的生存率明显高于低表达组（Ｐ＜０．０５）；腋淋巴结阴性组中，ｎｍ２３基因高、低表达的患者生存率差别显著，提示若将腋淋巴结阴性组中具有潜在转移危险性的ｎｍ２３低表达患者筛选出来，加强治疗，将会有助于提高生存率。应用Ｃｏｘ比例风险模型进行的多因素分析显示，ｎｍ２３基因表达与腋淋巴结转移、肿瘤大小均为乳腺癌的预后因素，其中ｎｍ２３基因高表达患者死亡的相对危险度较低表达患者低５４％。本研究结果提示，ｎｍ２３基因表达可以作为一项独立的预后指标，用以指导乳腺癌的临床治疗。     

VEGF的SNP状态预测贝伐株单抗治疗转移性结直肠癌的长期疗效

目的 检测转移性结直肠癌患者外周血血管内皮生长因子(VEGF)单核苷酸多态性(SNP),探讨VEGF的SNP与患者预后的关系.方法 60例转移性结直肠癌患者的外周血样本,均接受过标准的化疗,其中20例加用了贝伐珠单抗,应用MassARRAY方法,成功进行9个VEGF的SNP的检测,包括-2578C＞A、-460T＞C、-1455T＞C、-1154G＞A、-634G＞C、-398G＞A、-497T＞C、-2455 ＞-T、-936C＞T.结果 60例转移性结直肠癌患者,联合靶向治疗组的总生存期优于单用化疗组(P=0.01),VEGF各SNP变异率与NDBI数据库相似,-1455T＞C变异率极低,无临床价值;-2578C＞A和-460C＞T变异具有较高一致性;入组患者中SNP-497TT纯合子患者总生存期劣于其他患者(P=0.02);应用贝伐株单抗患者,SNP-497 3种基因型总生存期均有明显差异(P=0.01),SNP-398AA纯合变异者总生存期优于其他患者(P=0.02)SNP-2455 CC纯合子者总生存期优于其他患者(P=0.01).结论 在转移性结直肠癌,外周血VEGF的SNP状态与贝伐珠单抗以及化疗的长期疗效可能相关,需要进一步增加病例,加强这方面的研究.     

Evaluation of the potential for lymph node metastasis using CRP 1846C>T genetic polymorphism in invasive breast cancer

Lymph node status is a key indicator of the best approach to treatment of invasive breast cancer. However, the accuracy with which lymph node metastasis is diagnosed is not currently satisfactory. New and more reliable methods that enable one to know who has a greater potential for lymph node metastasis would be highly desirable. We previously reported that lymph node involvement in esophageal and lung cancer may have a genetic component: C-reactive protein (CRP) 1846C?>?T genetic polymorphism. Here we examined the diagnostic value of CRP 1846C?>?T polymorphism for assessing the risk of lymph node metastasis in cases of invasive breast cancer. The study participants were 185 women with invasive breast cancer who underwent curative surgery with lymph node dissection. Using DNA from blood samples and polymerase chain reaction–restriction fragment length polymorphism, the utility of CRP genetic 1846C?>?T polymorphism (rs1205) for assessing the risk of lymph node metastasis was evaluated. Fifty-two (28 %) patients had lymph node metastasis. After the patients were divided into two groups based on their CRP 1846 genotypes (C/C?+?C/T and T/T), the clinical characteristics did not differ between the groups, but there was a significantly greater incidence of lymph node metastasis among patients in the T/T group. Moreover, the odds ratio for lymph node involvement in patients carrying the 1846 T/T genotype was more than 2.2 in multivariate logistic regression models. CRP genetic polymorphism may be a novel predictor of the risk of lymph node metastasis in invasive breast cancer.