糖尿病与癌症发病及死亡风险的人群研究进展

0 引言 糖尿病的高患病率及多种并发症使其成为世界范围内的一个严重的公共卫生问题,而癌症已成为继心血管疾病的全球第二大死亡原因,因此,糖尿病对癌症的影响即使轻微亦可在人群中造成严重的后果.近10年来,糖尿病与癌症的关系得到了较广泛的调查研究,许多病例对照研究及队列研究但不是所有的研究显示糖尿病及其治疗药物与癌症关联[1],其机制可能是高血糖、高胰岛素血症和慢性炎症.本文就其相关流行病学证据做一综述以指导临床上对糖尿病诊治的决策.     

糖尿病对肺癌的影响、作用机制及糖代谢调节治疗

肺癌是世界范围内发病率最高的癌症,也是癌症死因之首。近年来随着人们生活方式、饮食习惯改变以及人口老龄化进程加快,高血糖、高血脂、肥胖、高血压等代谢异常疾病的发病率逐年攀升。大量研究证实糖尿病与包括肺癌在内的多种癌症的发生发展及预后紧密相关,但其具体相关性及其作用机制尚未完全明确。本文将从糖尿病与肺癌的流行病学研究、糖尿病和降糖药物对肺癌的影响和可能的作用机制、糖尿病肺癌患者糖代谢治疗等方面进行综述。     

二甲双胍降低糖尿病患者肿瘤发病风险及机制的研究进展北大核心CSCD

糖尿病患者罹患各类癌症的风险明显高于正常人,但其原因和机制仍不十分清楚,目前认为与高血糖、高胰岛素血症、胰岛素抵抗等因素相关。另外流行病学研究还提示糖尿病的治疗与癌症的发病率和死亡率有一定的关系,胰岛素或磺脲类药物因能增加体内胰岛素水平或加重胰岛素抵抗而使癌症风险增加,二甲双胍可能因为减轻胰岛素抵抗及血浆胰岛素水平而与癌症风险降低相关。本文就二甲双胍抗肿瘤分子机制的相关进展进行综述。     

角鲨烯环氧化酶与癌症的研究进展

角鲨烯环氧化酶（SQLE）是胆固醇合成途径中的限速酶和关键控制点。越来越多的证据表明，SQLE与多种癌症的发生、发展、转移和不良预后密切相关。SQLE不仅可促进癌细胞的增殖和上皮间质转化，还在维持肿瘤干细胞干性及调节人体胆固醇稳态中发挥重要作用。SQLE可能是癌症治疗潜在的分子靶点。本文概述了SQLE在人体内胆固醇稳态调节中的作用，以及SQLE在多种癌症发生发展及转移中的作用及分子机制。筛选新型SQLE抑制剂可能为癌症靶向治疗提供新思路。     

巨噬细胞抑制因子-1与癌症相关恶病质

0 引言 癌症相关恶病质(cancer-associated cachexia,CAC)是各种晚期癌症患者的主要并发症,约80％的晚期癌症患者存在厌食和体重下降等症状,约22％的癌症患者直接死于由恶病质引起的心肺功能衰竭,而非癌症本身[1].由于CAC在晚期癌症患者中普遍存在,它已成为影响晚期癌症患者生活质量和生存预后的主要因素,探讨CAC的发病机制及有效的防治措施,对提高癌症患者的生活质量及降低其病死率具有十分重要的意义.研究发现,巨噬细胞抑制因子-1(macrophage inhibitory cytokine-1,MIC-1)是与食欲直接相关的细胞因子,下调MIC-1的表达可逆转癌症相关性厌食及体重下降[2].随着越来越多的证据表明MIC-1在大多数癌症中普遍存在,并且在癌症的发生发展中起着重要作用,其干预食欲及体重的机制也在进一步被证实和深入研究中.目前国内有关MIC-1在CAC防治中的研究报道极少,该文主要综述国外的相关研究现状,为国内进一步研究MIC-1在防治CAC中的作用机制提供依据.     

糖尿病与肿瘤关系的研究进展

2型糖尿病和肿瘤是两类严重威胁人类健康的慢性疾病。大量的流行病学和临床研究表明,2型糖尿病患者肝癌、胰腺癌、子宫内膜癌、胆囊癌、结直肠癌和乳腺癌的风险增加。高血糖可通过多种直接和间接机制促进癌细胞增殖、迁移、侵袭和免疫逃逸。胰岛素抵抗和高胰岛素血症会通过胰岛素/IGF-I信号轴激活多条信号通路促进肿瘤发生。持续的慢性炎性反应可通过DNA损伤和促炎因子促进癌症的发生发展。肠道菌群失调主要与几种消化道肿瘤发生密切相关。本文将对2型糖尿病与恶性肿瘤发生发展的关系及可能的机制研究进展进行综述。     

肿瘤患者继发真菌感染的研究进展

癌症患者并发真菌感染,原因包括患者本身的因素及治疗相关的因素.念珠菌属是主要的致病真菌.治疗策略主要包括预防性治疗、先期治疗、经验性治疗和直接治疗.目前抗真菌药物主要是通过破坏真菌细胞壁、细胞膜或者影响核酸合成起作用,而真菌耐药的机制可能与基因有关.白细胞减少、真菌血症等是伴发真菌感染肿瘤患者的死亡危险因素.     

肿瘤患者继发真菌感染的研究进展

癌症患者并发真菌感染，原因包括患者本身的因素及治疗相关的因素。念珠菌属是主要的致病真菌。治疗策略主要包括预防性治疗、先期治疗、经验性治疗和直接治疗。目前抗真菌药物主要是通过破坏真菌细胞壁、细胞膜或者影响核酸合成起作用，而真菌耐药的机制可能与基因有关。白细胞减少、真菌血症等是伴发真菌感染肿瘤患者的死亡危险因素。     

二甲双胍与肿瘤相关性的新观点与挑战

2型糖尿病（T2DM）是一种慢性疾病,在全球范围内迅速增长,它是各类癌症的重要风险因素。而二甲双胍是治疗T2DM最常用的处方药。通过流行病学和临床研究表明,使用二甲双胍可以降低T2DM患者的癌症风险,改善癌症患者的预后和生存率。此外,二甲双胍在癌症治疗中的临床试验正在扩大到非糖尿病人群。越来越多的研究者认为二甲双胍将会成为癌症预防和治疗的一个有吸引力的候选药物。在这里,我们总结了近年来二甲双胍在肿瘤预防与治疗中的流行病学证据与相关研究进展、二甲双胍的抗肿瘤机制,并探讨了提高二甲双胍对肿瘤的敏感性和预防肿瘤转移的可能性。     

中医药对癌症支持性治疗的科学证据

辅助与替代疗法已被越来越多用于已发展国家的癌症患者。在各种另类疗法中,只有少数像中医药般既具坚实理论、又有完备的治病方法,包括对癌症的治疗。近年,许多证据表明中医药是有效的癌症支持性治疗,可在常规治疗的治疗期间和治疗后应用。本文特归纳一些已发表的临床报告和荟萃分析,综述中医药治疗方案对癌症支持性治疗的证据,其中包括中药材、针灸和气功治疗。     

Diabetes mellitus and cancer risk: Review of the epidemiological evidence

Diabetes mellitus and cancer are diseases of epidemic proportions across the globe. These diseases are influenced by many factors, both genetic and environmental. A possible association between diabetes and cancer risk has long been speculated. Increased incidence of several cancers has been observed in diabetes patients, notably pancreatic, hepatic, colorectal, breast, urinary tract, and endometrial cancers. In contrast, a decreased incidence of prostate cancer is observed in diabetes patients, implying a protective effect. Precise knowledge of the complex associations and interactions between these two conditions is of great importance for their prevention and treatment. Multiple potential mechanisms have been proposed, but they have tended to be site‐specific. Possible common mechanisms for a biological link between diabetes and cancer include hyperinsulinemia, hyperglycemia, and inflammation. Today, 366 million people live with diabetes globally, and this figure is expected to increase. Thus, if diabetes is associated with even a small increase in cancer risk, this may have important consequences at the population level. The aim of this review is to summarize recent epidemiological evidence of an association between diabetes and total cancer and specific sites of cancer, and to consider causal associations between these diseases. (Cancer Sci 2013; 104: 9–14)     

From obesity to diabetes and cancer: epidemiological links and role of therapies

Increasing evidence suggests a complex relationship between obesity, diabetes and cancer. Here we review the evidence for the association between obesity and diabetes and a wide range of cancer types. In many cases the evidence for a positive association is strong, but for other cancer types a more complex picture emerges with some site-specific cancers associated with obesity but not to diabetes, and some associated with type I but not type II diabetes. The evidence therefore suggests the existence of cumulative common and differential mechanisms influencing the relationship between these diseases. Importantly, we highlight the influence of antidiabetics on cancer and antineoplastic agents on diabetes and in particular that antineoplastic targeting of insulin/IGF-1 signalling induces hyperglycaemia that often evolves to overt diabetes. Overall, a coincidence of diabetes and cancer worsens outcome and increases mortality. Future epidemiology should consider dose and time of exposure to both disease and treatment, and should classify cancers by their molecular signatures. Well-controlled studies on the development of diabetes upon cancer treatment are necessary and should identify the underlying mechanisms responsible for these reciprocal interactions. Given the global epidemic of diabetes, preventing both cancer occurrence in diabetics and the onset of diabetes in cancer patients will translate into a substantial socioeconomic benefit.     

Exposures in childhood,adolescence and early adulthood and breast cancer risk: a systematic review of the literature

A growing body of work indicates that exposures over the life course have important roles to play in the aetiology of breast cancer. This review synthesises the literature that has been published in the area of early life events and female breast cancer risk. The review finds some evidence, primarily from cohort studies on the relationship between birthweight and breast cancer, to suggest that in utero events are related to breast cancer risk in adulthood. Strong evidence to support a positive association between height and breast cancer exists. Postulated mechanisms for this relationship include the role of early diet in subsequent disease risk, and the influence of endogenous growth factors mediating the relationship. There is some evidence to suggest that leg length is the component of height which is generating the observed associations between height and breast cancer. There is no consistent pattern of association between relative weight in childhood or adolescence and risk of breast cancer. The evidence to suggest an association between physical activity in early life and breast cancer risk is convincing from case-control studies, but is not fully substantiated by the results of three cohort studies. There are inconsistent results regarding the association between smoking at a young age and breast cancer risk. There is little evidence for an association between passive smoking in early life and breast cancer risk. No clear association between early drinking and breast cancer risk exists. These results are discussed in relation to possible underlying mechanisms and health promotion strategies which could reduce breast cancer risk.     

Metabolic Syndrome and Breast Cancer Risk: Is There a Role for Metformin?

Obesity is one of the most important known preventable causes of cancer, accounting for up to 20% of cancer deaths in women. Obese women have increased risk of dying from breast cancer as well as an increased risk of distant metastasis. Metabolic Syndrome (MetSyn) is a group of metabolic conditions that include 1) abdominal obesity, 2) atherogenic dyslipidemia, 3) elevated blood pressure, and 4) insulin resistance. MetSyn is known to promote the development of cardiovascular disease and diabetes and may be associated with increased breast cancer risk. Emerging evidence supports an association between mammary adipocytes and their secreted adipocytokines and breast cancer initiation and progression. Metformin (1,1-dimethylbiguanide hydrochloride) is a drug used to treat type 2 diabetes and MetSyn. We review the potential association between MetSyn in promoting breast cancer and emerging evidence for the use of metformin in cancer prevention.     

Obesity and cancer: the risks, science, and potential management strategies

Overweight and obesity increase the risk of developing several cancers. Once cancer develops, individuals may be at increased risk of recurrence and poorer survival if they are overweight or obese. A statistically significant association between overweight or obesity and breast cancer recurrence or survival has been observed in the majority of population-based case series; however, adiposity has been shown to have less of an effect on prognosis in the clinical trial setting. Weight gain after breast cancer diagnosis may also be associated with decreased prognosis. New evidence suggests that overweight/obesity vs normal weight may increase the risk of poor prognosis among resected colon cancer patients and the risk of chemical recurrence inprostate cancer patients. Furthermore, obese cancer patients are at increased risk for developing problems following surgery, including wound complication, lymphedema, second cancers, and the chronic diseases affecting obese individuals without cancer such as cardiovascular disease and diabetes. Mechanisms proposed to explain the association between obesity and reduced prognosis include adipose tissue-induced increased concentrations of estrogens and testosterone, insulin, bioavailable insulin-like growth factors, leptin, and cytokines. Additional proposed mechanisms include reduced immune functioning, chemotherapy dosing, and differences in diet and physical activity in obese and nonobese patients. There have been no randomized clinical trials testing the effect of weight loss on recurrence or survival in overweight or obese cancer patients, however. In the absence of clinical trial data, normal weight, overweight, and obese patients should be advised to avoid weight gain through the cancer treatment process. In addition, weight loss is probably safe, and perhaps helpful, for overweight and obese cancer survivors who are otherwise healthy.     

Report of the Japan Diabetes Society/Japanese Cancer Association joint committee on diabetes and cancer

In recent years, diabetes has been shown to be associated with cancer risk, and this has led to a joint committee being formed, enlisting experts from the Japan Diabetes Society and the Japanese Cancer Association to address this issue. Epidemiological data in Japan provides evidence to demonstrate that diabetes is associated with increased risk for cancers, especially colorectal, liver, and pancreatic cancers. The mechanisms through which diabetes is assumed to promote oncogenesis include insulin resistance and associated hyperinsulinemia, hyperglycemia, and inflammation. Common risk factors for type 2 diabetes and cancer include aging, male sex, obesity, physical inactivity, inappropriate diet (excessive red/processed meat intake, inadequate vegetable/fruit/dietary fiber intake), excessive alcohol drinking, and smoking. Given that inappropriate diet/exercise, smoking and excessive alcohol drinking are common risk factors for diabetes and cancer, diet/exercise therapy, smoking cessation and alcohol moderation may be associated with decreased risk for cancer in diabetic patients. There is as yet limited evidence as to whether any particular antidiabetic agents may influence cancer risk.     

Diabetes and cancer I: risk, survival, and implications for screening

Type 2 diabetes mellitus (DM) and cancer are common diseases that are frequently diagnosed in the same individual. An association between the two conditions has long been postulated. Here, we review the epidemiological evidence for increased risk of cancer, decreased cancer survival, and decreased rates of cancer screening in diabetic patients. The risk for several cancers, including cancers of the pancreas, liver, colorectum, breast, urinary tract, and endometrium, is increased in patients with DM. In a pooled risk analysis weighting published meta-analytic relative risk (RR) for individual cancer by differences in their incidence rates, we found a population RR of 0.97 (95?% CI, 0.75-1.25) in men and 1.29 (95?% CI, 1.16-1.44) in women. All meta-analyses showed an increased relative risk for cancer in diabetic men, except studies of prostate cancer, in which a protective effect was observed. The relationship between diabetes and cancer appears to be complex, and at present, a clear temporal relationship between the two conditions cannot be defined. DM also impacts negatively on cancer-related survival outcomes and cancer screening rates. The overwhelming evidence for lower cancer screening rates, increased incidence of certain cancers, and poorer prognosis after cancer diagnosis in diabetic patients dictates a need for improved cancer care in diabetic individuals through improved screening measures, development of risk assessment tools, and consideration of cancer prevention strategies in diabetic patients. Part two of this review focuses on the biological and pharmacological mechanisms that may account for the association between DM and cancer.     

Diabetes and Cancer: A Consensus Report

Epidemiologic evidence suggests that cancer incidence is associated with diabetes as well as certain diabetes risk factors and treatments. This consensus statement of experts assembled jointly by the American Diabetes Association and the American Cancer Society reviews the state of science concerning 1) the association between diabetes and cancer incidence or prognosis; 2) risk factors common to both diabetes and cancer; 3) possible biologic links between diabetes and cancer risk; and 4) whether diabetes treatments influence the risk of cancer or cancer prognosis. In addition, key unanswered questions for future research are posed. CA Cancer J Clin 2010. © 2010 American Cancer Society, Inc.