原发性高血压遗传流行病学研究

目的探讨原发性高血压的遗传模式。方法对117个原发性高血压家系用分离分析法和多基因阈值理论进行遗传模式的研究。结果常染色体显性遗传和隐性遗传模式的统计学检验均具有显著意义（P〈0.05）;资料中子女高血压发病情况分析显示,此病不符合性连锁遗传方式;多基因阈值分析的遗传率为74.83%。结论原发性高血压为多基因遗传疾病,平均遗传度为74.83%±4.28%,对有遗传易感性人群应重点管理,加强防治。     

消化性溃疡的遗传流行病学研究

用遗传流行病学方法调查分析了男性消化性溃疡患者及对照者一级亲属消化性溃疡及其它疾病的发病率。消化性溃疡患者亲属中男女性消化性溃疡的发病率分别为8.13%（27/332）和3.37%（10/297）,而对照亲属中则分别为2.25%（5/222）和0.43%（1/234）。消化性溃疡病患者男、女亲属患病的相对危险度分别为3.84（P<0.01）和8.12（P<0.05）。用Falconer法计算得男女消化性溃疡的遗传度分别为49.27±8.22%和54.41±9.50%。经分层分析,病例组吸烟又饮酒的男性亲属中消化性溃疡的发病率（10.49%）及遗传度（67.44±11.26%）明显高于不吸烟且不饮酒的亲属（4.60%,25.57±19.21%）,提示遗传因素与环境因素在消化性溃疡的发病中具有协同作用。     

寻常型银屑病遗传流行病学研究

报道了200个寻常型银屑病家系的遗传学研究结果。先证者一级亲属患病率为4.69%,二级亲属患病率为1.02%,分别是北京地区一般人群患病率（0.30%）的15.6倍和3.4倍。银屑病遗传度估计值加权平均为60.4%,说明遗传因素起重要作用。发病年龄影响因素分析结果表明,女性发病年龄提前4.0岁,父母患病时先证者发病年龄提前8.4岁;此外,发病年龄与患者出生时父亲年龄呈显著负相关。     

家族性乳腺癌遗传易感基因研究现状

家族性乳腺癌与遗传易感基因的突变有密切的联系,目前已发现多种乳腺癌遗传易感基因,它们分别定位于１７号和１３号染色体的长臂和８号染色体的短臂上。乳腺癌家族中易感基因突变携带患乳腺癌的危险性明显高于普通人群,具有不同易感基因突变的乳腺癌患其组织学特征也有所不同。本就家族性乳腺癌遗传易感基因的研究进展作一综述。     

家族性乳腺癌遗传易感基因研究现状

家族性乳腺癌与遗传易感基因的突变有密切的联系 ,目前已发现多种乳腺癌遗传易感基因 ,它们分别定位于 17号和 13号染色体的长臂和 8号染色体的短臂上。乳腺癌家族中易感基因突变携带者患乳腺癌的危险性明显高于普通人群 ,具有不同易感基因突变的乳腺癌患者其组织学特征也有所不同。本文就家族性乳腺癌遗传易感基因的研究进展作一综述     

CDT1和GMNN基因多态性与女性乳腺癌危险性的关联研究

目的探讨参与DNA复制的两个重要基因CDTI和GMNN基因多态性与我国人群散发乳腺癌的关联。方法采用病例对照研究设计，研究对象包括427例乳腺癌患者及477名无肿瘤史的正常对照组。采用聚合酶链反应-限制性片段长度多态性，方法测定CDT 1838G／A，错配聚合酶链反应-限制性片段长度多态性方法测定GMNN 387C／A的基因型。结果CDT1GG、GA和AA3种基因型以及GMNN CC、CA和从3种基因型在病例组和对照组的频率分布差异无统计学意义（P值分别为0．619和0．793）。然而，分层分析发现，在有肿瘤家族史的人群中，CDT1 GA＋AA基因型可显著增加乳腺癌的危险性（调整OR：2．21，95％CI：1．20～4．09）。结论CDT1 838G／A基因多态性和GMNN 387C／A基因多态性与总的散发性乳腺癌无显著关联，但CDT 1838G／A可能对于具有遗传背景的女性乳腺癌的易感性具有一定的作用。     

偏头痛的遗传流行病学研究进展

偏头痛的患病率较高，但临床就诊率不高。国内对于偏头痛的研究往往局限于诊断、治疗、药理等方面，遗传学方面的研究几乎是空白。为提高大家对偏头痛遗传学方面的认识，本文对近年有关偏头痛遗传模式、遗传基础及遗传与环境交互作用的研究进展进行了综述。     

Genetic epidemiology of early onset breast cancer.

Risks for breast cancer when there is a family history of the disease are usually calculated using data from segregation analyses which favour a single dominant gene with high penetrance. There are, however, at least three loci known to be associated with familial breast cancer (p53, BRCA1, and an as yet unpublished locus) and the frequencies and penetrances of these genes are not likely to be the same. We have attempted to address the problem of which genetic parameters should be used to calculate risks for different patterns of familial breast cancer. Data from 384 nuclear families ascertained through a proband selected for early onset breast cancer were subjected to complex segregation analysis, correcting for ascertainment bias resulting from selection for severe phenotype. Age of onset of breast cancer, incorporated as severity, provides additional information to the segregation model over and above that given by assigning liability classes on the basis of age at observation. The use of this additional parameter in the analysis is described. There is fair agreement between estimates from this sample and previous predictions from consecutive probands and consultands. The differences suggest more than one rare dominant gene for susceptibility to breast cancer, with different penetrances. Although refinements of segregation analysis will help to delineate these different genes, perfect resolution will require identification of the mutant alleles. Methods to estimate genetic parameters under genotype specific mortality need to be developed. Meanwhile, we suggest that high and low estimates of penetrance be used in risk estimation for genetic counselling, and as a guide to candidates for entry into clinical trials of screening and chemoprevention in breast cancer.     

Genetic epidemiology of breast cancer in Britain

A complex segregation analysis was conducted on two British series (one consecutive series of probands with breast cancer and one series ascertained through a normal consultand). Altogether there were 1248 nuclear families with breast cancer. A dominant gene with a frequency of 0-003 giving a lifetime penetrance of 0-83 is favoured. Ovarian, endometrial and cancers associated with the SBLA syndrome, as well as benign breast disease, were significantly more common in familial breast cancer than in families of single cases. Probands in families with more than one individual with breast cancer were non-significantly younger than isolated probands.     

A feasibility study to evaluate breast cancer patients’ knowledge of their diagnosis and treatment

Objective

To evaluate the feasibility of an electronic survey to assess patients’ knowledge of their breast cancer and treatment, and interest in receiving a medical summary.

Methods

Women undergoing breast cancer treatment completed an interviewer-administered electronic survey in person or by telephone. Medical records were abstracted to evaluate knowledge accuracy.

Results

Among 38 eligible patients approached for the study, 35 (92%) participated and 33 (94%) completed the survey. Participants’ perceived knowledge tended to be greater than their actual knowledge. Reporting of clinicopathologic features was most accurate for stage (91%) and lymph node status (88%), and least accurate for tumor size (61%), type (61%), and grade (33%). Accurate reporting of tumor receptor over-expression varied from 76% (estrogen receptor) to 39% (progesterone receptor). Many patients correctly recalled general treatment modalities and details of surgery; fewer recalled details of radiation and chemotherapy. Importantly, nearly all (32/33) were interested in receiving a breast cancer medical summary.

Conclusion

An electronic survey is feasible to assess breast cancer patients’ knowledge. This data suggest that patients have gaps in knowledge and would like a personalized medical summary.

Practice implications

Larger studies are needed to validate and characterize knowledge gaps, and test interventions to improve physician–patient information sharing.     

A computer model for the study of breast cancer

A computer model was designed as a relational database to assess breast cancer screening in a cohort of women where the growth and development of breast cancer originates with the first malignant cell. The concepts of thresholds for growth, axillary spread, and distant sites are integrated. With tumor diagnosis, staging was performed that includes clinical and sub-clinical states. The model was parameterized to have staging characteristics similar to data published by the Surveillance, Epidemiology, and End-Results (SEER) Program. Validation was accomplished by comparing simulated staging results with non-SEER sources, and simulated survival with independent clinical survival data.     

Diagnosis analysis in breast cancer and cervical cancer screening

Assessment of the accuracy of diagnostic procedures has been made independent of the diagnostic criteria used by means of Relative Operating Characteristics (ROC) analysis. A ROC curve describes the mutual relationship between the sensitivity and specificity of a diagnostic decision on the basis of various diagnostic criteria. The construction of such ROC curves is made possible if diagnoses are graded into levels of certainty. The curve enables the choice of an operating point with predetermined sensitivity and specificity values for the diagnosis decision. The population-based breast-cancer and cervical cancer screening projects carried out in Utrecht demonstrated an excellent fit between actual data and the calculated ROC curves. Analysis of the accuracy or performance of cytological diagnosis uncovered a problem arising from the similarly graded histopathological reference criteria used to determine the 'truth' of the cytological diagnosis decisions. The proposed solution is a serial calculation of ROC curves, one for each level differentiating between the histopathological categories. The ensuing three-dimensional ROC hill may reveal a summit marking numerically advantageous diagnosis criterion levels for both the test and the disease to be detected, or a depression signalling locally below-standard detection performance.     

The effect of tissue fixation and processing on breast cancer size

Precise measurement of an invasive breast cancer is crucial for pathological staging and subsequent patient management. Formalin fixation and histological processing may change tissue size, but there is no agreement on which state of the specimen, fresh or fixed, should be used for final tumor measurement. To determine the influence of fixation and processing on breast tumor size, a specific 1-dimensional measurement from 50 invasive breast tumors was recorded in fresh, fixed, and processed/mounted states. Tumors varied in maximum measured dimension from 4 to 20 mm and contained 10% to 90% estimated fibrous tissue (mean, 52.8%). In 96% of cases, there was no difference in measured size between fresh and fixed states. After final processing and mounting, a decrease in size from initial fresh measurement was noted in 40% of cases (mean difference, 2.4 mm; maximum difference, 7 mm). In 9 cases (18%), the measured size increased by a maximum of 3 mm (mean, 1.7 mm) after processing/mounting. Twenty-one cases (42%) showed no change in measurement during the entire fixation and processing protocol. Increases in measured size were attributed largely to tissue expansion during histological sectioning/mounting. One can arguably measure the size of an invasive breast cancer from either the fresh or fixed state without affecting accuracy, but caution should be exercised in relying solely on the microscopic measurements.     

Rosai-Dorfman disease of the breast mimicking cancer

Rosai-Dorfman disease or sinus histiocytosis with massive lymphadenopathy is a rare proliferative histiocytic disorder of the lymph nodes. Extranodal involvement occurs in a considerable number of cases; however, involvement of the breast is very rare, and it is even rarer for the lesion to be localized in the breast alone without affecting any other sites. This report describes the case of a 50-year-old Brazilian woman with a lump confined to her left breast that had clinical and radiological characteristics indistinguishable from cancer. The proliferation of histiocytes, displaying lymphophagocytosis and an S-100 protein immunophenotype on a core biopsy of the lesion, led to a diagnosis of Rosai-Dorfman disease and permitted conservative therapy. Recognition of this rare condition, when occurring at an unexpected site such as the breast, is difficult, and the correct diagnosis is important prior to therapeutic management.     

Prognostic significance of peritumoral vessel invasion in clinical trials of adjuvant therapy for breast cancer with axillary lymph node metastasis

To assess the prognostic significance of peritumoral vessel invasion, data were examined for 1,510 women entered into the Ludwig Breast Cancer Group Trials I to IV evaluating adjuvant therapy for operable breast cancer with axillary nodal metastasis. Vessel invasion by tumor cells was identified by routine light microscopy in 59 per cent (889 of 1,510) of the patients and was equally distributed between premenopausal/perimenopausal (60 per cent, 468 of 778) and postmenopausal (58 per cent, 421 of 732) women. In logrank analyses stratified by nodal status (one to three or four or more positive nodes), the four-year disease-free survival (DFS) rate was significantly lower in patients with vessel invasion than in women without vessel invasion (50 per cent versus 65 per cent, P less than 0.0001). This DFS difference was seen for both premenopausal/perimenopausal (P = 0.0004) and postmenopausal (P = 0.0002) patients. The four-year overall survival rate was also lower in patients with vessel invasion (71 per cent versus 82 per cent, P = 0.0006), both for premenopausal/perimenopausal (P = 0.002) and postmenopausal (P = 0.04) women. The presence of vessel invasion was significantly associated with increasing numbers of positive axillary lymph nodes, rising tumor grade, nonstellate tumor border growth pattern, and higher steroid hormone receptor content of the primary tumor. The assessment of peritumoral vessel invasion continued to have prognostic significance for DFS (P less than 0.0001) and overall survival (P = 0.003) when evaluated in multivariate models controlling for treatment assigned, nodal status, tumor size, estrogen receptor status, menopausal status, and age. Depending on the subpopulation, patients with vessel invasion had a 41 per cent to 54 per cent greater risk of treatment failure than those without vessel invasion and a 29 per cent to 64 per cent greater risk of death. The percentage of treatment failures at distant sites was higher for women with than for those without vessel invasion (27 per cent versus 18 per cent, P = 0.003). In patients with axillary lymph node metastases, peritumoral vessel invasion may be a sign of increased systemic disease burden.     

乳腺癌患者抑郁情绪的相关因素分析

目的研究乳腺癌患者抑郁情绪及其影响因素。方法采用抑郁自评量表（SDS）、艾森克个性问卷（EPQ）、简易应对方式问卷（SCSQ）、自编医护辅导调查表进行测评。测评86例乳腺癌患者的抑郁情绪、人格、应对方式、医护辅导并作相关分析和多元线性逐步回归分析。结果乳腺癌患者SDS平均分为47.76±7.38,且抑郁情绪与神经质、消极应对呈正相关（r=0.47,0.27,P〈0.01）,与内外向、积极应对、医护辅导呈负相关（r=-0.41,-0.25,-0.24,P〈0.01）,进入抑郁评分为因变量的回归方程的因素依次有神经质、内外向、积极应对、消极应对、医护辅导（R=0.57,R2=0.32,P〈0.01）。结论神经质、内外向、积极应对、消极应对、医护辅导是影响乳腺癌患者抑郁情绪的主要因素。