Contested Etiology and Fragile Castles: An Ethnography of Cancer Risk and Cancer Research in Two Parts

Culture, Medicine, and Psychiatry -     

Etiology of the supernormal period.

In many excitable cells, there is a time after the action potential when the threshold for eliciting a second action potential is lower than it is in the steady state. The Hodgkin and Huxley (1952) equations predict such a supernormal period. Using their model, it is shown that the supernormal period results from the slow kinetics of the potassium current and does not depend on sodium current activation or inactivation or on the after-depolarization.     

基于全基因组关联的中国常见肿瘤遗传病因学研究

肿瘤是基因-环境交互作用引起的复杂性疾病.在同样的环境暴露下,不同遗传背景的个体发生肿瘤的风险有很大差异.研究肿瘤相关遗传因素对理解肿瘤发生发展乃至诊断治疗都有重要意义.近年来发展的全基因组关联研究(genome-wide association study,GWAS)可在全基因组范围内发现与复杂疾病或表型关联的遗传因素,为复杂疾病遗传学研究提供了强有力的手段.欧美研究者运用全基因组关联研究的方法,对各种常见肿瘤进行了研究,获得了重要成果.2010年以来,中国科学家在国际核心期刊发表了一系列高水平的肿瘤全基因组关联研究成果,在中国常见肿瘤的遗传病因学研究方面取得了重要进展.     

宫颈癌研究新进展

宫颈癌是威胁女性健康的最常见的主要恶性肿瘤之一,据统计全世界每年新发现有数万女性患有宫颈癌这种癌症,越来越多的妇女死于宫颈癌。宫颈癌也是一种预防的肿瘤,其致病因素多种多样,包括初次性生活的年龄、吸烟、HPV、HSV、HCMV、EBV等因素。目前的检测方法有巴氏涂片法、薄层液基细胞学涂片法、宫颈组织活检及宫颈管刮术、HPV-DNA检测、计算机辅助细胞学检测系统等方法可以诊断宫颈癌。早期诊断、早期检查对宫颈癌的预防和治疗具有积极作用,同时降低宫颈癌的死亡率。     

Insights into Pancreatic Cancer Etiology from Pathway Analysis of Genome-Wide Association Study Data

Background

Pancreatic cancer is the fourth leading cause of cancer death in the U.S. and the etiology of this highly lethal disease has not been well defined. To identify genetic susceptibility factors for pancreatic cancer, we conducted pathway analysis of genome-wide association study (GWAS) data in 3,141 pancreatic cancer patients and 3,367 controls with European ancestry.

Methods

Using the gene set ridge regression in association studies (GRASS) method, we analyzed 197 pathways identified from the Kyoto Encyclopedia of Genes and Genomes database. We used the logistic kernel machine (LKM) test to identify major contributing genes to each pathway. We conducted functional enrichment analysis of the most significant genes (P<0.01) using the Database for Annotation, Visualization, and Integrated Discovery (DAVID).

Results

Two pathways were significantly associated with risk of pancreatic cancer after adjusting for multiple comparisons (P<0.00025) and in replication testing: neuroactive ligand-receptor interaction, (Ps<0.00002), and the olfactory transduction pathway (P = 0.0001). LKM test identified four genes that were significantly associated with risk of pancreatic cancer after Bonferroni correction (P<1×10⁻⁵): ABO, HNF1A, OR13C4, and SHH. Functional enrichment analysis using DAVID consistently found the G protein-coupled receptor signaling pathway (including both neuroactive ligand-receptor interaction and olfactory transduction pathways) to be the most significant pathway for pancreatic cancer risk in this study population.

Conclusion

These novel findings provide new perspectives on genetic susceptibility to and molecular mechanisms of pancreatic cancer.     

Contested Etiology: Cancer Risk Among Two Anatolian Populations in Turkey and Europe

This paper discusses the different explanatory models and the contested perceptions of cancer etiology among residents of two Anatolian villages and migrants from these villages in Turkey, Sweden, and Germany. These communities suffer from an endemic, deadly cancer called mesothelioma, the cause of which is associated with exposure to an environmental carcinogenic substance, erionite, which is present in large deposits in the ground, in the stones, and white stucco that the villagers used to build their homes, and in the air in the form of dust. However, an examination of patients' disease trends, experiences, and local explanations has led to new investigations of possible familial risk cofactors. This paper selectively focuses on different aspects of cancer risk and its manifested metaphors, aesthetics, and perceptions. The different categories of cancer risk freely interact, derive an important part of their meaning from the context of the doctor-cancer patient relationship, and are created and navigated by the cancer narrative.     

Etiology of shock in blunt trauma.

Patients who have suffered blunt trauma and present in shock of uncertain cause represent a problem frequently encountered by emergency physicians. A retrospective review of the charts of 879 patients who had suffered blunt trauma and presented to a regional trauma unit over a 44-month period revealed that 154 of the patients had presented to either a hospital or the trauma unit in shock. The most common causes of shock when a single source of hemorrhage was identified were, in order of decreasing frequency, intraperitoneal hemorrhage, pelvic or other musculoskeletal fractures, thoracic hemorrhage, severe head injury and spinal cord injury. Severe head injuries accounted for only 8% of the single-source cases and contributed to shock in only seven of the remaining cases.     

Pulmonary renal syndromes. II. Etiology and pathogenesis.

Numerous systemic diseases share immunopathogenic mechanisms. This article reviews the proposed etiologies and immunopathogenic mechanisms of a group of diseases which share pulmonary and renal abnormalities. Specifically, we discuss the following diseases: Good-pasture''s syndrome, systemic lupus erythematosus, progressive systemic sclerosis, Wegener''s granulomatosis, lymphomatoid granulomatosis, and Churg-Strauss syndrome.     

Etiology of breast cancer. II. Epidemiologic aspects

The epidemiology of breast cancer is reviewed with particular emphasis on its etiology. A number of studies suggest that differences in breast cancer incidence are associated with differences in marital status, number of pregnancies, age at menarche, age at menopause, height and weight, socioeconomic status, geographic location and residence. However, in no case is the evidence adequate to establish a “cause and effect” relationship. The genetic component of these associations may be of primary importance, while other conditions such as marital status are probably indirect reflections of the operation of more fundamental factors.There is a general consensus that endocrine factors play an important part in mammary cancer occurrence. At present, the association between breast cancer and the presence of the virus-like (type B) particles in human milk is not established.