乳腺癌家族聚集性的遗传流行病学研究——危险因素、分离比、遗传度分析

目的 研究遗传因素在乳腺癌发生中的作用。方法 采用１：１匹配的病例对照研究方法，。从我国四个城市的主要医院收集了１９９６年１０月￣１９９７年１月间入院的乳腺癌新发病例及其对照计３１３对，并对其进行家系调查。采用Ｌｏｇｉｓｔｉｃ回归分析方法进行乳腺癌危险因素分析。采用Ｌｉ－Ｍａｎｔｅｌ－Ｇａｒｔ法进行乳腺癌分离比的估算，采用Ｆａｌｃｏｎｅｒ回归法进行遗传度估算。结果 乳腺部家族史是一显著的危险因素，     

武威市胃癌家族聚集性研究

目的 :探讨胃癌家族聚集现象。方法 :用二项分布 (p +q)n数学模型拟合 ,用 χ2 进行配合适度检验。结果 :武威市 4 4个家族中的胃癌分布超过了二项分布的概率范围 (χ2 =15 81,P <0 0 0 5 )。结论 :高发家族的胃癌发病存在家族聚集性     

广东籍鼻咽癌患者家族聚集性研究

目的研究高发区广东省鼻咽癌的家族聚集性规律,为反映高发区鼻咽癌的遗传流行病学特点及遗传咨询提供资料。方法收集1998年1月~2000年8月在中山大学肿瘤防治中心治疗的全部广东籍初诊鼻咽癌患者共1142例的病案资料。按照事先制定的调查表,收集患者的一般资料及家族中的肿瘤情况。结果在广东籍人群中,21.9%的鼻咽癌患者具有肿瘤家族史,其中12.3%的患者有鼻咽癌家族史。家族中肿瘤患者70%左右发生于一级亲属中,家族中鼻咽癌患者在父母和兄弟姐妹中发生的比率相当。广东省内高发区的患者亲属同患鼻咽癌的比例为19.8%,明显高于省内其他地区同患鼻咽癌的比例8.5%,χ2=0.236,P<0.01。结论在鼻咽癌高发区广东省,鼻咽癌具有显著的家族聚集性,而且越高发的地区其家族聚集性越强。     

上海市区食管癌家族聚集性研究

目的研究上海市区食管癌家族聚集性。方法用全人群病例┐对照研究方法，调查９０２例３０～７４岁食管癌新发病例，按频数配对随机配以１５５２例对照。结果食管癌家族史是食管癌的危险因素，男女相对危险度达到２～３左右，食管癌发病风险随着一级亲属患病人数的增多而增加（趋势检验Ｐ＜０．００１）。食管癌家族史调整人群归因危险度男性、女性分别为８．３％、９．２％。经过Ｌｉ┐Ｍａｎｔｅｌ┐Ｇａｒｔ法计算食管癌分离比为３．８３％（９５％ＣＩ＝３．１２％～４．４８％），提示属多基因遗传。根据Ｆａｌｃｏｎｅｒ方法，男性、女性遗传度分别为３３．２％±５．３％，３８．４％±３．６％，男女合并为３５．７％±２．２％。结论上海市区食管癌存在家族聚集现象。食管癌家族史增加食管癌发病风险。研究表明尽管遗传因素在食管癌的发生中起一定作用，但食管癌的发病风险主要来自环境因素。     

家族性聚集性鼻咽癌4例报告

国内有关父子、母子及兄妹同患鼻咽癌的报道 ,但母子及叔侄一家四口二代同患鼻咽癌笔者未见报道 ,现报道如下 :1　病例报告患者甲 ,男 ,37岁 ,于 1990年 12月开始出现鼻塞、鼻衄并伴有双颈部淋巴结肿大。ＣＴ检查诊断为鼻咽癌 ,病理证实 :低分化鳞癌。经常规放射治疗和化疗后 ,     

TNF-a基因多态性与广西肝癌家族聚集性的相关性研究

目的研究肿瘤坏死因子基因TNF—a-308、TNF-a-238与广西肝癌家族聚集性的关系。方法在广西肝癌高发区选取12个肝癌高发家族（124例）及与之相对应的12个非肿瘤对照家族（129例）为研究对象,采用SNP芯片技术检测两组中TNF—a-308、TNF—a-238的基因型及等位基因频率。结果肝癌高发家族组TNF-a-308G／A基因型分布频率高于对照家族组,差异有统计学意义（22．6％ vs 11．6％,x2=5．376,P=0．020）;肝癌高发家族组TNF-a-308A等位基因分布频率亦高于对照家族组,差异有统计学意义（11.3％VS5．8％,x2=4．877,P=0．024）。两组TNF-a-238基因型频率及等位基因频率差异均无统计学意义（P〉0．05）。结论TNF—a-308基因多态性可能与广西肝癌家族聚集性相关,携带TNF-a-308A等位基因可能会增加肝癌高发家族成员患肝癌的风险;TNF—a-238基因多态性与广西肝癌家族聚集无统计学关联。     

GSTM1、GSTT1基因多态性与家族聚集性肝癌的遗传易感性研究

目的探讨GSTM1、GSTT1基因多态性与家族聚集性肝癌遗传易感性的关系。方法应用PCR技术检测GSTM1、GSTF1在家族聚集性肝癌和肝癌高发家系的基因表型。结果家族聚集性肝癌组GSTM1（-）、GSTT1（-）基因型频率分别为68．8％、47．5％,显著高于非家族聚集性肝癌组（54．6％、30．8％）和对照肝组织组（53．3％、25．3％）（P〈0．05）;随着家族中患肝癌病例数的增加,GSTM1（-）、GSTT1（-）基因型的频率逐渐升高,肝癌高发家系组GSTM1（-）、GSTT1（-）基因型频率分别为68．1％和44．9％,显著高于对照家系组（47．5％、25．0％）（P〈0．05）。若将GSTM1（-）T1（-）基因型视为危险暴露因素．．家族聚集性肝癌组GSTM1（＋）T1（＋）和GSTM1（＋）T1（-）／GSTM1（-）T1（＋）基因型频率均显著低于非家族聚集性肝癌组和对照肝组织组（P〈0．01）。结论GSTMI、GSTF1遗传多态性与家族聚集性肝癌的遗传易感性有关,GSTM1（-）、GSTT1（-）基因型可能是肝癌家族成员的危险暴露因素。     

HBV Infection and Familial Aggregation of Liver Cancer: An Analysis of Case-Control Family Study

OBJECTIVES: Hepatitis B virus (HBV) infection is one of the most important risk factors for hepatocellular carcinoma (HCC). The specific aim of this study is to assess the influence of HBV infection on familial aggregation of HCC. METHODS: We conducted a population-based case-control family study of liver cancer in Taixing, China, in 2001-2002, with a total of 3611 individuals from 202 case families and 202 control families. Conditional logistic regression was used for the case-control data. The approach of GEE2 was used to analyze the family data and age and sex were adjusted in all marginal regression models. RESULTS: The odds ratio for HBV associated with HCC was 41.39 (95% confidence interval (CI): 23.03-74.30). The relatives of cases had a higher risk of liver cancer compared with the relatives of controls with a conditional odds-ratio of 3.06 (95% CI: 1.48-6.33). The association parameters among first- and second-degree relatives were no longer statistically significant when HbsAg was taken into consideration. CONCLUSION: HBV infection was likely a main reason for the familial aggregation of liver cancer in Southern China.     

Genetic Screening for Familial Gastric Cancer

Approximately 10% of gastric cancer cases show familial clustering but only 1-3% of gastric carcinomas arise as a result of inherited gastric cancer predisposition syndromes. Direct proof that Hereditary Gastric Cancer a genetic disease with a germline gene defect has come from the demonstration of co-segregation of germline E-cadherin (CDH1) mutations with early onset diffuse gastric cancer in families with an autosomal dominant pattern of inheritance (HDGC). E-cadherin is a transmembrane calcium-dependent cell-adhesion molecule involved in cell-junction formation and the maintenance of epithelial integrity. In this review, we describe frequency and type of CDH1 mutations in sporadic and familial gastric cancer. Further we demonstrate the functional significance of some CDH1 germline missense mutations found in HDGC. We also discuss the CDH1 polymorphisms that have been associated to gastric cancer. We report other types of malignancies associated to HDGC, besides diffuse gastric cancer. Moreover, we review the data available on putative alternative candidate genes screened in familial gastric cancer. Finally, we briefly discuss the role of low-penetrance genes and Helicobacter pylori in gastric cancer. This knowledge is a fundamental step towards accurate genetic counselling, in which a highly specialised pre-symptomatic therapeutic intervention should be offered.     

Familial Cervical Cancer: Case Reports,Review and Clinical Implications

We report three Dutch families with familial clustering of (pre)neoplastic cervical disease, review the literature on familial risks of cervical intraepithelial neoplasia (CIN) and cervical cancer, and discuss possible practical guidelines for women with a family history of cervical cancer. Daughters and sisters of women with cervical cancer have been reported to have a relative risk of 1.5-2.3 to develop this type of cancer. From a practical clinical point of view, we suggest that as in women with an increased non-genetic risk to develop cervical cancer (e.g. because of immunosuppressive therapy) increased surveillance to detect this tumour should be considered in women with an increased risk based on family history. Cessation of smoking should be advised. As the use of condoms at least prevents HPV re-infection its use can be recommended as a way to lower the cervical cancer risk. Future studies to determine the genetic contribution to the development of cervical cancer should include the paternal family history of cancer and, because genetic predisposition might express itself as a higher risk to develop precursors of cervical cancer, carcinoma in situ and CIN grade II-III.     

Familial characteristics of autoimmune and hematologic disorders in 8,406 multiple myeloma patients: a population-based case-control study

A population-based case-control study was conducted to evaluate risk of developing multiple myeloma (MM) associated with personal history of autoimmune diseases and occurrence of autoimmune and selected hematologic disorders in first-degree relatives. Data were obtained for all (n = 8,406) MM cases diagnosed in Sweden (1958-1998), with linkable relatives, 16,543 matched controls and first-degree relatives of cases (n = 22,490) and controls (n = 44,436). Odds ratios (ORs) were calculated to quantify the risk of MM in relation to personal/family history of 32 autoimmune disorders. Familial aggregation of malignancies was evaluated in a marginal survival model using relatives as the cohort. The risk for MM was significantly elevated among subjects with a personal history of pernicious anemia (OR = 3.27; 2.22-4.83) and individuals with a family history of systemic lupus erythematosus (OR = 2.66; 1.12-6.32). Compared with controls, relative risk (RR) of MM was significantly increased (RR = 1.67; 1.02-2.73) in relatives of cases, particularly relatives of probands aged > or =65 at diagnosis (RR = 2.50; 1.19-5.27). Risks were nearly 4-fold elevated among female relatives (RR = 3.97; 1.54-10.2) and among relatives of female probands (RR = 3.74; 1.58-8.83). MM cases had more cases of monoclonal gammopathy of undetermined significance (MGUS) among their relatives than controls, but the numbers were too small to be conclusive. There was generally no increase in risk of MM in probands whose relatives had hematologic malignancies other than MM. These findings do not support a strong association between personal/familial autoimmune diseases and MM. However, MM itself shows significant familial aggregation, implicating the etiologic importance of this type of hematological neoplasm and perhaps MGUS in germ line genes.     

Familial association of pancreatic cancer with other malignancies in Swedish families

Background:

The aim of this study was to characterise the familial association of pancreatic cancer with other malignancies.

Methods:

Relative risks (RRs) of pancreatic cancer according to family history of cancer were calculated using the updated Swedish Family-Cancer Database, which includes over 11.5 million individuals. Estimates were based on Poisson regression. RRs of tumours for individuals with a parental history of pancreatic cancer were also estimated.

Results:

The risk of pancreatic cancer was elevated in individuals with a parental history of cancers of the liver (RR 1.41; 95% CI 1.10–1.81), kidney (RR 1.37; 95% CI 1.06–1.76), lung (RR 1.50; 95% CI 1.27–1.79) and larynx (RR 1.98; 95% CI 1.19–3.28). Associations were also found between parental history of pancreatic cancer and cancers of the small intestine, colon, breast, lung, testis and cervix in offspring. There was an increased risk of pancreatic cancer associated with early-onset breast cancer in siblings.

Conclusion:

Pancreatic cancer aggregates in families with several types of cancer. Smoking may contribute to the familial aggregation of pancreatic and lung tumours, and the familial clustering of pancreatic and breast cancer could be partially explained by inherited mutations in the BRCA2 gene.     

胃癌新辅助化疗研究进展

新辅助化疗可以减小肿瘤负荷,降低临床病期,提高肿瘤的手术切除率.该文主要对近年来新辅助化疗在胃癌治疗中的现状进行了综述.     

p53在弥漫型胃癌中的表达研究

[目的]研究 p53蛋白表达在胃癌预后中的意义。[方法]采用免疫组织化学LSAB法 ,对152例胃癌组织中 p53蛋白表达进行检测 ,分析 p53表达与临床病理因素及预后之间的关系。[结果]p53蛋白表达阳性率为24 3%(37/152) ,其表达与胃癌各临床病理因素之间无明显相关性。p53表达在肠型胃癌与弥漫型胃癌之间不同 ,生存率分析显示 ,p53表达的不良预后者仅见于弥漫型胃癌而非肠型胃癌。[结论]p53蛋白表达可用于识别弥漫型胃癌中具侵袭性并伴不良预后的亚组胃癌病例     

胃癌与遗传

胃癌的遗传分两种形式,一种为家族性遗传模式(即强易感性),另一种为人群基础的遗传模式(即弱易感性).胃癌发生与癌基因激活和肿瘤抑制基因失活有关,但并非是两者的简单综合体.胃癌转移和预后也明显受患者遗传背景的影响,如E-cadherin、基质金属蛋白酶等.胃癌与遗传(基因)学研究是一个系统的、全面的过程,单个基因、单个通路难以解释癌症复杂的生物学行为.