TOX3基因单核苷酸多态与乳腺癌风险的相关性Meta分析

目的对多个乳腺癌病例对照研究的样本进行Meta分析,探讨TOX3基因单核苷酸多态与乳腺癌风险的关系。方法全面检索相关文献,收集2005年1月至2011年3月发表的关于TOX3基因rs3803662位点多态性与乳腺癌易感性的病例对照研究,采用Stata11.0统计软件包进行Meta分析。结果最终纳入病例对照研究7项,累计病例24 464例,对照32 353例。除了杂合子模型(OR=1.12,95%CI:0.99-1.27),纯合子(OR=1.34,95%CI:1.43～1.59)、显性遗传(OR=1.16,95%CI:1.03～1.31)、隐性遗传(OR=1.25,95%CI:1.10～1.42)模型中结果均有统计学意义。结论 TOX3基因rs3803662位点的多态性可能是乳腺癌的危险因素。②高加索人群的TOX3基因rs3803662位点突变的纯合子模型和隐形遗传模型可能会增加人群患乳腺癌的危险性,纯合子基因型TT是乳腺癌的危险因素。     

老年与非老年食管癌、贲门癌术后呼吸功能不全关系的Meta分析

目的综合评价国内年龄对食管癌、贲门癌术后并发呼吸功能不全的影响。方法应用Meta分析的固定效应和随机效应模型,针对5篇有关年龄与食管癌、贲门癌术后并发呼吸功能不全关系的病例对照研究进行综合分析,共累计病例203例,对照634例,计算合并优势比(OR)及其95%的可信区间(95%CI)。结果年龄与食管癌、贲门癌术后并发呼吸功能不全之间总合并OR为2.69(95%CI:1.86～3.87)。结论高龄是食管癌、贲门癌术后并发呼吸功能不全的危险因素之一。年龄≥65岁的患者术后并发呼吸功能不全是年龄<65岁患者的2.69倍。     

200例女性乳腺癌患者患病影响因素的分析

目的了解乳腺癌患者的危险、保护因素。方法采用病例对照研究方法,抽取100对在年龄、文化程度、职业、居住地等方面相配对的妇女进行问卷调查,并进行统计学分析。结果经分析得出：存在不和谐的生活事件（OR=2．878）、已绝经妇女（OR=1．340）、有乳腺疾病史（OR=8．706）及结婚年龄越大（OR=1．215）为女性患乳腺癌的危险因素;而多吃玉米（OR=0．363）和产后母乳喂养婴儿（OR=0．269）为患乳腺癌的保护因素。结论影响女性乳腺癌患者患病的因素是多样的,对于不和谐的生活事件、饮食等因素还有待深入探讨。     

吸烟与食管癌关系的Meta分析

应用 Meta-analysis方法对国内有关吸烟与食管癌关系的 10个研究结果进行定量综合分析 ,采用随机效应模型 (D-L法 )计算合并比值比 (OR)及其 95 %的可信区间 (95 % CI)。结果显示 ,吸烟的合并 OR为 1.97(95 % CI:1.67～ 2 .3 1) ,提示吸烟是我国食管癌的危险因素。     

大豆异黄酮的摄入与乳腺癌发病率关系的Meta分析

目的:探讨饮食摄入大豆异黄酮与乳腺癌发病率的关系。方法:使用Stata11.0软件应用Meta分析的方法,对近13年来国内外发表的关于大豆异黄酮摄入与乳腺癌发病率的病例对照研究资料,异质性检验,合并OR,并进行偏倚评估与敏感性检验。结果:纳入本次Meta分析的病例对照研究一共有10项,其中包括4500名乳腺癌病例。以摄入大豆异黄酮的量分为常食组与偶食组,异质性检验结果为I231%,采用固定效应模型,合并OR=0.89,95%CI为0.81-0.97,Z=2.55,P=0.011,结果具有统计学意义。结论:常摄入大豆异黄酮能降低乳腺癌的发病率,是乳腺癌发生的保护性因素。     

动物性食品和植物性食品在大肠癌危险因素中的作用Meta分析

目的:综合分析饮食在我国大肠癌发病危险因素中的作用。方法:运用Meta-analysis方法对国内(1994~2006年)有关大肠癌危险因素的6个1:1配对病例对照研究结果进行了定量综合分析,累计病例、对照数分别为1508和1508例,统计处理采用Dersi-monian和Laird的随机效应模型,数据分析采用SAS9.1.3统计软件分析。结果:长时间食用动物性食品而少摄入蔬菜水果这一类的植物性食品可以导致患大肠癌的危险性提高,而植物性食品则为保护因素(综合OR均小于0.7)。结论:长时间食用动物性食品使患大肠癌的危险增加,而多食用蔬菜水果杂粮类植物性食品会降低患大肠癌的危险。     

交叉设计多中心临床试验的混合效应模型

目的 :探讨交叉设计多中心临床试验资料的分析方法。方法 :采用混合效应的一般线性模型和混合效应的广义线性模型。结果 :将个体作为随机效应来估计时 ,可以增加误差自由度 ,提高估计精度 ,同时可以考虑中心效应、患者的年龄、性别、基线等协变量的影响 ,并且对于缺失数据在不丢失信息的情况下照样能进行分析。结论 :在交叉设计多中心临床试验资料的分析中 ,混合效应的一般线性模型适用于连续性结果变量的分析 ,混合效应的广义线性模型适用于分类结果变量的分析。     

HBV感染与肝癌关系的Meta分析

目的:探讨我国人群HBV感染与肝癌的关联程度,为预防决策提供依据。方法:采用Meta分析法,对根据纳入标准和排除标准筛选出的24篇关于HBV感染与原发性肝癌关系的病例对照研究资料进行定量综合分析,比较固定效应模型和随机效应模型合并OR值的差异,比较剔除质量较差文献前后结论的差异,以评价Meta分析结果的稳定性。发表偏移的识别主要有漏斗图分析、线性回归法和失安全系数。结果:异质性检验χ2=29.59,P=0.16,采用固定效应模型进行Meta分析,合并OR=11.81,95%CI为10.33~13.50。结论:HBV感染与肝癌呈高度相关,我国居民应加强乙肝疫苗的免疫接种。     

289 例Luminal B 型乳腺癌患者预后的相关因素分析

目的探讨Luminal B型乳腺癌患者预后的影响因素。方法收集2015年1月—2016年12月我院收治的289例Luminal B型乳腺癌患者的临床及随访资料,对血小板/淋巴细胞比值(PLR)、红细胞体积分布宽度(RDW)行受试者工作特征(ROC)曲线分析,计数资料采用χ^2检验及Fisher确切概率法,Kaplan-Meier法绘制生存曲线,组间比较采用Log-rank检验,预后分析采用COX多因素回归模型。结果高、低PLR组乳腺癌患者的无病生存率(DFS)分别为82%(77/94)、94.9%(185/195),高、低RDW组乳腺癌患者DFS分别为85.3%(139/163)、97.6%(123/126)。单因素分析显示,生育史、腋窝淋巴结、病理分期、脉管癌栓、PLR、RDW、辅助化疗、内分泌治疗是影响Luminal B型乳腺癌患者预后的危险因素(P<0.05)。COX多因素分析显示,生育史、RDW、辅助化疗、内分泌治疗是影响Luminal B型乳腺癌患者预后的独立危险因素(P<0.05)。结论Luminal B型乳腺癌术前RDW测定具有一定的预测价值,RDW升高可提示预后不良;无生育史或首次生育年龄≥35岁的Luminal B型乳腺癌患者复发风险较高。     

建立阿奇霉素在中国健康人群中的群体药代动力学模型

目的建立中国人群中阿奇霉素(大环内酯类抗生素)的群体药代动力学模型。方法对20例健康自愿者的血药浓度和生化指标,用非线性混合效应模型法进行群体药代动力学分析,估算药代动力学参数,分析固定效应的影响以及个体内/间的变异,建立群体药代动力学模型。结果口服阿奇霉素呈一级吸收的二室模型,体质量对CL1和CL2及年龄对V1均有影响。结论用非线性混合效应模型法建立的中国人群中阿奇霉素的群体药代动力学模型,结构稳定,预测准确。     

Beta glucan induces proliferation and activation of monocytes in peripheral blood of patients with advanced breast cancer

AIM: Glucans are glucose polymers that constitute a structural part of fungal cell wall. They can stimulate the innate immunity by activation of monocytes/macrophages. In human studies it has been shown that beta glucan has an immunomodulatory effect and can increase the efficacy of the biological therapies in cancer patients. In this prospective clinical trial we assessed in vivo effects of short term oral beta glucan administration on peripheral blood monocytes and their expression of activation markers in patients with advanced breast cancer. METHODS: 23 female patients with advanced breast cancer were included in the study. Median age of the patients was 52 years. Sixteen healthy females with a median age of 48 years served as the control group for comparing the initial blood samples. Peripheral blood samples were drawn on day zero and patients started receiving oral 1-3, 1-6, D-beta glucan daily. Blood samples were recollected on the 15th day. In the initial samples mean lymphocyte count was significantly lower in the patients with breast cancer (1281+/-306/mm(3) versus 1930+/-573/mm(3), p=0.04). In the patients with breast cancer, mean monocyte count which was 326+124/mm(3) at the beginning, was increased to 496+194/mm(3) at the 15th day (p=0.015). Expression of CD95 (Apo1/Fas) on CD14 positive monocytes was 48.17% at the beginning, which was increased to 69.23 % at the 15th day (p=0.002). Expression of CD45RA on CD14 positive monocytes was 49.9% at the beginning; it was increased significantly to 61.52% on day 15 (p=0.001). CONCLUSION: Oral beta glucan administration seems to stimulate proliferation and activation of peripheral blood monocytes in vivo in patients with advanced breast cancer.     

BRCA-1和Twist在乳腺癌中的表达及其相关性分析

目的研究BRCA-1,Twist在乳腺癌组织中的表达及与乳腺癌临床病理参数的关系,了解两者表达的相关性。方法应用免疫组织化学法检测BRCA-1,Twist在66例乳腺癌组织的表达。结果乳腺癌中Twist的阳性表达与肿瘤的大小、患者年龄、组织学分级无明显相关性(P>0.05),与淋巴结转移率及Ki67的表达率呈正相关(P<0.05)。BRCA-1的阳性表达与组织学分级、肿瘤大小、患者年龄及Ki67的表达率呈负相关(P<0.05),与淋巴结转移率无明显相关性(P>0.05)。BRCA-1,Twist在乳腺癌中的表达呈负相关(r=-0.5,P<0.05)。结论在乳腺癌组织中联合检测Twist,BRCA-1有望成为预测肿瘤预后的生物学指标。     

Cytochrome P450 CYP1B1 and catechol O-methyltransferase (COMT) genetic polymorphisms and breast cancer susceptibility in a Turkish population

Epidemiological studies indicate that most risk factors for breast cancer are related to reproductive and hormonal factors. Estrogen has been proposed to trigger breast cancer development via an initiating mechanism involving its metabolite, catechol estrogen (CE). Because of the important role of cytochrome P450 1B1 ( CYP1B1) and catechol O-methyltransferase ( COMT) in mammary estrogen and carcinogen metabolism, we examined the CYP1B1 and COMT genes to determine whether genetic variations could account for inter-individual differences in breast cancer. In this case-control study, we determined CYP1B1 and COMT genotypes in 84 breast cancer patients and 103 healthy unrelated women controls from a Turkish population. In the case of CYP1B1, we genotyped CYP1B1*3 (L432 V) allele. We found that carriers of the CYP1B1*3 allele were more frequent among breast cancer patients with adjusted odds ratio (OR) for age, age at menarche, age at first full-term pregnancy, body mass index (BMI) and smoking status of 2.32 (95% confidence interval 1.26-4.25) associated with the allele. However, this allele appeared to be a significant factor for susceptibility only in patients with a BMI greater than 24 kg/m(2). Menopausal status did not appear to affect susceptibility. In the case of COMT, there was no significant difference in susceptibility for breast cancer development between patients with low activity COMT-L (V158 M) allele and high activity COMT-H allele, and susceptibility was not affected by menopausal status, BMI or CYP1B1 genotype. We conclude that the CYP1B1* 3 allele appears to be a factor for susceptibility to breast cancer in Turkish women especially those with a BMI greater than 24 kg/m(2).     

Gail乳腺癌风险评估模型应用初探

目的：了解Gail乳腺癌风险评估模型在深圳市宝安区范围内评估乳腺癌高危人群的应用价值。方法：回顾性调查103例乳腺癌患者及317例正常对照组的年龄、乳腺疾病史、家族史、初潮年龄、初产年龄、乳腺活检情况、种族等资料,应用Gail乳腺癌风险评估模型回顾性评估5年前乳腺癌发病风险,并分析模型的诊断试验的价值。结果：乳腺癌组中98例及正常对照组中20例,经模型评估后提示有5年内乳腺癌发病高风险。Gail模型应用的诊断试验评价结果为灵敏度0.951,特异度0.937,阳性预测值0.831。结论：Gail乳腺癌风险评估模型对乳腺癌发病高风险人群的预测价值较高,可作为社区乳腺癌筛查发现高风险人群的工具之一。     

Gail风险评估模型预测珠三角广佛地区女性散发性乳腺癌风险的适用性研究

目的 评估Gail风险评估模型预测珠三角广佛地区女性散发性乳腺癌风险的适用性及其临床效能。方 法 回顾性分析416例乳腺癌患者及170例乳腺良性增生患者5年前的临床资料,比较2组患者年龄、体质量指数 （BMI）、月经初潮年龄、初产年龄、绝经年龄、足月产次数、乳腺良性疾病手术史、雌激素替代治疗、乳房周期性疼痛、 乳腺癌家族病史、被动吸烟史、乳腺活检情况、种族等资料的差异。应用Gail乳腺癌风险评估模型测评工具评估5年 乳腺癌发病风险。结果 与乳腺良性增生组相比,乳腺癌组患者年龄偏大,BMI较高,月经初潮年龄延迟、初产年龄 和绝经年龄提前,绝经患者和乳房周期性疼痛患者的比例较高（均P＜0.05）。586例患者经Gail模型评估高风险为 247例（42.2%）,平均风险值（2.17±0.63）%;低风险者339例（57.8%）,平均风险值（1.25±0.36）%。Gail模型预测乳腺 癌患癌风险的敏感度45.4%,特异度65.8%,阳性预测值76.5%,阴性预测值33.9%,约登指数0.112。结论 Gail风险 评估模型对珠三角广佛地区女性散发性乳腺癌患病风险的评估尚不充分,大范围推广应用证据不足。     

NAT2 slow acetylation and GSTM1 null genotypes may increase postmenopausal breast cancer risk in long-term smoking women

N-acetyltransferase (NAT) 1 and 2 and glutathione S-transferase (GST) M1 and T1 are phase II enzymes that are important for activation and detoxification of carcinogenic heterocyclic and aromatic amines, as present in cigarette smoke. We studied whether genetic polymorphisms in these genes modifies the relationship between smoking and breast cancer. A nested case-control study was conducted among participants in a Dutch prospective cohort. Breast cancer cases (n=229) and controls (n=264) were frequency-matched on age, menopausal status and residence. Compared to never smoking, smoking 20 cigarettes or more per day increased breast cancer risk statistically significant only in postmenopausal women [odds ratio (OR)=2.17; 95% confidence interval (CI) 1.04-4.51]. Neither NAT1 slow genotype, or GSTT1 null genotype, alone or in combination with smoking, affected breast cancer risk. However, compared to individuals with rapid NAT2 genotype, women with the very slow acetylator genotype (NAT2*5), who smoked for 20 years showed an increased breast cancer risk (OR=2.29; 95% CI 1.06-4.95). Similarly, the presence of GSTM1 null genotype combined with high levels of cigarette smoking (OR=3.00; 95% CI 1.46-6.15) or long duration (OR=2.53; 95% CI 1.24-5.16), increased rates of breast cancer. The combined effect of GSTM1 null genotype and smoking high doses was most pronounced in postmenopausal women (OR=6.78; 95% CI 2.31-19.89). In conclusion, our results provide support for the view that women who smoke and who have a genetically determined reduced inactivation of carcinogens (GSTM1 null genotype or slow NAT2 genotype (especially very slow NAT2 genotype)) are at increased risk of breast cancer.     

早期乳腺癌新辅助化疗淋巴结转阴患者术后放疗的价值

目的 探讨乳腺癌术后放疗（PMRT）对新辅助化疗（NAC）后达到腋窝淋巴结阴性（ypN0）的临床 T1- 2N1M0期乳腺癌患者的治疗意义。方法 回顾性分析天津医科大学肿瘤医院2003—2013年收治的共187例在新辅 助化疗后达到ypN0的病理淋巴结阳性,临床分期T1-2N1M0同时接受手术治疗的乳腺癌患者的临床资料,所有入组 患者治疗前行淋巴结细针抽吸细胞活检（FNAB）进行病理分期。依据有无接受乳腺癌术后放疗将患者分为放疗组 （81例）和未放疗组（106例）,并对2组患者的临床病理特征进行分析统计。采用Kaplan-Meier法测定无局部复发生 存（LRRFS）率、无远处转移生存（DMFS）率、无疾病生存（DFS）率和总生存（OS）率的生存曲线,Cox回归分析患者上 述几个生存指标的预后影响因素。结果 PMRT治疗组DFS和DMFS获得显著改善（P＜0.05）,而LRRFS和OS组间 差异无统计学意义（P＞0.05）。NAC 后病理T 分期较早者、行PMRT 以及年龄≥40岁患者DMFS 和DFS 的预后较好 （P＜0.05）。软组织受累的患者LRRFS预后较差（P＜0.05）。结论 临床T1-2N1M0期乳腺癌NAC和改良根治术后 达到ypN0的乳腺癌患者总体生存情况较好,行术后放疗不能改善乳腺癌总生存质量和局部复发,但是能显著降低其 远处转移率以及提高无病生存率。     

39例男性乳腺癌患者预后因素分析

目的 探讨单一机构一定时间段内收治的男性乳腺癌患者病理特征及其预后分析.方法 整理收集2007年1月1日—2012年1月1日期间就诊于蚌埠医学院第一附属医院的男性乳腺癌病例,回顾性分析其临床特点及病理类型,及其相关因素对患者预后的影响.采用Kaplan-Meier法进行生存率估计,对于组间生存率的比较采用Log-rank检验,同时采用Cox比例风险回归模型进行预后因素的分析.结果 根据单因素分析结果显示,影响男性乳腺癌患者5年无病生存率的因素有:年龄分层(P=0.017)、淋巴结转移情况(P=0.006)、雌激素受体(ER)表达情况(P=0.002)、孕激素受体(PR)表达情况(P=0.003)以及肿瘤大小(P=0.025).年龄分层(P=0.027)、淋巴结转移情况(P=0.022)、ER表达情况(P=0.001)、PR表达情况(P=0.001)以及肿瘤直径大小(P=0.031)是影响男性乳腺癌患者总生存率的因素.根据多因素分析结果,年龄分层(HR=0.197,95.0％置信区间:0.057～0.680,P=0.010)与男性乳腺癌患者无病生存率相关.年龄分层(HR=0.191,95.0％置信区间:0.054～0.680,P=0.011)以及淋巴结转移情况(HR=1.841,95.0％置信区间:0.638～5.308,P=0.049)是男性乳腺癌患者的总生存率影响因素.结论 男性乳腺癌发病率较低,预后较差,在现阶段缺乏有效的治疗手段,提高早期检出率,争取早发现早治疗,是促进其良好预后的一大措施.     

Intron 3 16 bp duplication polymorphism of p53 is associated with an increased risk for breast cancer by the age of 50 years

We used a large population-based case-control study to determine whether three known p53 polymorphisms, intron 3 16 bp duplication, codon 72(Arg/Pro) and intron 6 MspI restriction fragment length polymorphism, alter the risk for breast cancer in German women. For all three polymorphisms, the odds ratios (ORs) for breast cancer were increased in women carrying the rare allele; however, this was statistically significant only for the 16 bp duplication polymorphism. Compared with the 16 bp duplication wild-type A1/A1 genotype, ORs for A1/A2 genotype and A2/A2 genotype were 1.3 [95% confidence interval (CI) 1.0-1.7] and 1.7 (95% CI 0.8-3.4), suggesting an allele dosage effect (trend test, P = 0.03). Significant evidence was found for a differential effect by family history of breast cancer (P = 0.03 for interaction), with the OR being 5.3 among women with a first degree family history. Our data suggest that inheritance of an intronic polymorphism in the p53 gene increases breast cancer risk appreciably in women by the age of 50 years with a family history of breast cancer in the German population.     

Gestational biomarkers of daughter’s breast cancer in the Child Health and Development Studies

We examined the link between gestational biomarkers and breast cancer in 9169 daughters born into the Child Health and Development Studies from 1959 to 1967. We identified 137 breast cancer cases diagnosed by age 52 as of 2012. Markers of increased risk included higher placental volume and rapid 2nd trimester gestational weight gain. Protective markers were placental hemorrhage and fibrin deposition, indicators of resistance to placental trophoblast invasion. Paradoxically, higher ponderal index at birth was protective suggesting that fetal and placental pathways to breast cancer are multiple and distinct. Results link placental and fetal phenotypes to breast cancer, characterizing some as restrictive and others as permissive markers of tumor development. We found new biomarkers of breast cancer risk that can be mined to discover ‘omic correlates in the pregnancy exposome using archived and contemporary pregnancy samples. This line of investigation may discover new pathways to risk and new opportunities for prevention.