Antibody-drug conjugates treatment of small cell lung cancer: advances in clinical research.

Small cell lung cancer (SCLC) is an extremely aggressive cancer with a relatively low median survival rate after diagnosis. Treatment options such as chemotherapy or combination immunotherapy have shown clinical benefits, but resistance and relapse can occur. Antibody-drug conjugates (ADCs), as a novel class of biopharmaceutical compounds, have broad application prospects in the treatment of SCLC. ADCs consist of monoclonal antibodies that specifically target cancer cells and are attached to cytotoxic drugs, allowing for targeted killing of cancer cells while sparing healthy tissues. Current clinical studies focus on Delta-like protein 3 (DLL3), CD56, Trophoblast cell surface antigen 2 (Trop-2), B7-H3, and SEZ6. Although toxicities exceeding expectations have been observed with Rova-T, drugs targeting TROP-2 (Sacituzumab Govitecan), B7-H3 (DS-7300), and SEZ6 (ABBV-011) have shown exciting clinical benefits. In this review, we collect the latest clinical evidence to describe the therapeutic efficacy and safety of ADCs in SCLC and discuss prospects and challenges.

HER3 receptor and its role in the therapeutic management of metastatic breast cancer.

Metastatic breast cancer (mBC) poses a significant threat to women's health and is a major cause of malignant neoplasms in women. Human epidermal growth factor receptor (HER)3, an integral member of the ErbB/HER receptor tyrosine kinase family, is a crucial activator of the phosphoinositide-3 kinase/protein kinase B signaling pathway. HER3 overexpression significantly contributes to the development of resistance to drugs targeting other HER receptors, such as HER2 and epidermal growth factor receptors, and plays a crucial role in the onset and progression of mBC. Recently, numerous HER3-targeted therapeutic agents, such as monoclonal antibodies (mAbs), bispecific antibodies (bAbs), and antibody-drug conjugates (ADCs), have emerged. However, the efficacy of HER3-targeted mAbs and bAbs is limited when used individually, and their combination may result in toxic adverse effects. On the other hand, ADCs are cytotoxic to cancer cells and can bind to target cells through antibodies, which highlights their use in targeted HER3 therapy for mBC. This review provides an overview of recent advancements in HER3 research, historical initiatives, and innovative approaches in targeted HER3 therapy for metastatic breast cancer. Evaluating the advantages and disadvantages of current methods may yield valuable insights and lessons.

Synergistic acceleration of machine learning and molecular docking for prostate-specific antigen ligand design.

Prostate-specific antigen (PSA) serves as a critical biomarker for the early detection and continuous monitoring of prostate cancer. However, commercial PSA detection methods primarily rely on antigen-antibody interactions, leading to issues such as high costs, stringent storage requirements, and potential cross-reactivity due to PSA variant sequence homology. This study is dedicated to the precise design and synthesis of molecular entities tailored for binding with PSA. By employing a million-level virtual screening to obtain potential PSA compounds and effectively guiding the synthesis using machine learning methods, the resulting lead compounds exhibit significantly improved binding affinity compared to those developed before by researchers using high-throughput screening for PSA, substantially reducing screening and development costs. Unlike antibody detection, the design of these small molecules offers promising avenues for advancing prostate cancer diagnostics. Furthermore, this study establishes a systematic framework for the rapid development of customized ligands that precisely target specific protein entities.

The safety and efficacy of anti-PD-1 inhibitor-based combinational therapy in non-small cell lung cancer patients with oncogenic alterations.

Background: The anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) immunotherapy has been extensively used in patients with non-small cell lung cancer (NSCLC) in which the tumors are negative for oncogenic alterations. However, whether PD-1/PD-L1 blockade therapy could be applicable in patients harboring oncogenic mutations is largely unknown. Methods: In this retrospective study, we analyzed the safety and efficacy of anti-PD-1 inhibitor-based combinational therapy in a NSCLC cohort of 84 patients who harbored oncogenic alterations in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), k-Ras, RET, HER2 and BRAF. The patients were followed up till disease progression or death. The adverse effects associated with the treatment were carefully evaluated and timely interrupted. Results: There were 50 patients harboring EGFR mutations, 17 patients with k-Ras mutation, 2 patients with ALK rearrangement, 6 patients with RET rearrangement, 6 patients with HER2 exon20 insertion and 3 patients with BRAF V600E mutation. About 58.8% of the k-Ras mutant patients responded to the combinational treatment. The median progression-free survival (mPFS) of the k-Ras cohort was 14 months, with the 12-month median overall survival (mOS) ratio and the 24-month OS ratio of 86.7% and 75.8%, respectively. Patients with EGFR exon21 L858R mutation or RET rearrangement tended to have a more favorable response, while patients harboring ALK rearrangement, HER2 exon20 insertion and BRAF V600E mutation did not respond well to anti-PD-1 inhibitor-based combinational therapy. The incidence of treatment-related toxicity was 52.3% and the most common immune-related adverse events (irAEs) were PD-1 inhibitors-related hypothyroidism and pneumonitis. The PD-L1 status and lung immune prognostic index (LIPI) could be used as biomarkers dictating therapeutic outcomes of the combinational therapy. Conclusions: The anti-PD-1 inhibitor-based combinational therapy elicited exciting anti-tumor efficacy and prolonged patient survival with manageable adverse effects in NSCLC patients harboring oncogenic alterations. The PD-L1 status and LIPI could be used as a biomarker predicting response to anti-PD-1 inhibitor-based combinational treatment in these patients.

Subtype recognition and identification of a prognosis model characterized by antibody-dependent cell phagocytosis-related genes in breast cancer.

BACKGROUND: Breast cancer (BC) is a heterogeneous tumor with a variety of etiology and clinical features. Antibody-dependent cell phagocytosis (ADCP) is the last step of immune checkpoint inhibition (ICI), and macrophages detect and recognize tumor cells, then destroy and engulf tumor cells. Despite the large number, negative regulators that inhibit phagocytic activity are still a key obstacle to the full efficacy of ICI. PATIENTS AND METHODS: An ADCP-related risk score prognostic model for risk stratification as well as prognosis prediction was established in the Cancer Genome Atlas (TCGA) cohort. The predictive value of ADCP risk score in prognosis and immunotherapy was also further validated in the TCGA along with International Cancer Genome Consortium cohorts. To promote the clinical application of the risk score, a nomogram was established, with its effectiveness verified by different methods. RESULTS: In this study, the genes collected from previous studies were defined as ADCP-related genes. In BC patients, two ADCP-related subtypes were identified. The immune characteristics and prognostic stratification were significant different between them. CONCLUSIONS: We identified two subtypes associated with ADCP gene expression in breast cancer. They have significant differences in immune cells, molecular functions, HLA family genes, immune scores, stromal scores, and inflammatory gene expression, which have important guiding significance for the selection of clinical treatment methods. At the same time, we constructed a risk model based on ADCP, and the risk score can be used as a good indicator of prognosis, providing potential therapeutic advantages for chemotherapy and immunotherapy, thus helping the clinical decision-making of BC patients.

Treatment Advances in Lung Cancer with Leptomeningeal Metastasis.

Leptomeningeal metastasis (LM) is a serious and often fatal complication in patients with advanced lung cancer, resulting in significant neurological deficits, decreased quality of life, and a poor prognosis. This article summarizes current research advances in treating lung cancer with meningeal metastases, discusses clinical challenges, and explores treatment strategies. Through an extensive review of relevant clinical trial reports and screening of recent conference abstracts, we collected clinical data on treating patients with lung cancer with meningeal metastases to provide an overview of the current research progress. Exciting progress has been made by focusing on specific mutations within lung cancer, including the use of EGFR tyrosine kinase inhibitors or inhibitors for anaplastic lymphoma kinase gene rearrangement, such as osimertinib, alectinib, and lorlatinib. These targeted therapies have shown impressive results in penetrating the central nervous system (CNS). Regarding whole-brain radiotherapy, there is currently some controversy among investigators regarding its effect on survival. Additionally, immune checkpoint inhibitors (ICIs) have demonstrated reliable clinical benefits due to their ability to retain anticancer activity in CNS metastases. Moreover, combination therapy shows promise in providing further treatment possibilities. Considerable progress has been made in the clinical research of lung cancer with LM. However, the sample size of prospective clinical trials investigating LM for lung cancer is still limited, with most reports being retrospective. Developing more effective management protocols for metastatic LM in lung cancer remains an ongoing challenge for the future.

m5 C and m6 A modification of long noncoding NKILA accelerates cholangiocarcinoma progression via the miR-582-3p-YAP1 axis.

Cholangiocarcinoma (CCA) is a severe malignancy originating from the bile duct and the second most common primary liver cancer. NF-kappa B interacting lncRNA (NKILA) is a functional lncRNA, which play important role in human cancers. However, the role and underlying mechanism of NKILA in CCA remains largely unknown. Here, our study demonstrated that NKILA was significantly upregulated in CCA tissues and cells. Overexpression of NKILA is associated with advanced TNM stage, lymph node and distant metastasis, and also indicated poor prognosis in CCA patients. Functionally, NKILA facilitated CCA growth and metastasis in vitro and in vivo. The 5-methylcytosine (m5 C) methyltransferase NSUN2 interacts with NKILA, increasing its m5 C level and promoting its interaction with YBX1. Moreover, NKILA physically interacted with and suppressed miR-582-3p, which was regulated by METTL3-mediated N6 -methyladenosine (m6 A) modification. Finally, we showed that YAP1 was a target of NKILA via miR-582-3p and NKILA functioned partially via YAP1 in CCA. Taken together, our findings indicate a novel regulatory mechanism of NKILA for promoting CCA progression and that NKILA may be a promising target for CCA treatment.

Cucurbituril-Ferrocene: Host-Guest Based Pretargeted Positron Emission Tomography in a Xenograft Model.

Pretargeted positron emission tomography is a macromolecule-driven nuclear medicine technique that involves targeting a preadministered antigen target-bound macromolecule with a radioligand in vivo, aiming to minimize the overall radiation dose. This study investigates the use of antibody based host-guest chemistry methodology for pretargeted positron emission tomography. We hypothesize that the novel pretargeting approach reported here overcomes the challenges the current pretargeting platforms have with the in vivo stability and modularity of the pretargeting components. A cucurbit[7]uril host molecule modified, anti-carcinoembryonic antigen antibody (M5A; CB7-M5A) and a 68Ga-radiolabeled ferrocene guest radioligand ([68Ga]Ga-NOTA-PEG3-NMe2-Fc) were studied as potential host-guest chemistry pretargeting agents for positron emission tomography in BxPC3 xenografted nude mice. The viability of the platform was studied via in vivo biodistribution and positron emission tomography. Tumor uptake of [68Ga]Ga-NOTA-PEG3-NMe2-Fc was significantly higher in mice which received CB7-M5A prior to the radioligand injection (pretargeted) (3.3 ± 0.7%ID/g) compared to mice which only received the radioligand (nonpretargeted) (0.2 ± 0.1%ID/g).

Prediction of 10-year atherosclerotic cardiovascular disease risk among community residents in Shanghai, China - a comparative analysis of risk algorithms.

BACKGROUND AND AIMS: The accuracy of various 10-year atherosclerotic cardiovascular disease (ASCVD) risk models has been debatable. We compared two risk algorithms and explored clustering patterns across different risk stratifications among community residents in Shanghai. METHODS AND RESULTS: A total of 28,201 residents (aged 40-74 years old) who were free of ASCVD were selected from the Shanghai Survey in China. The 10-year ASCVD risk was estimated by applying the 2013 Pooled Cohort Equations (PCEs) and Prediction for ASCVD Risk in China (China-PAR). The agreement was assessed between PCEs and China-PAR using Cohen's kappa statistics. The mean absolute 10-year ASCVD risk calculated by PCEs and China-PAR was about 10.0% and 6.0%, respectively. PCEs estimated that 44.9% of participants [with a 95% confidence interval (CI):44.0%-45.8%] were at high risk, while China-PAR estimated only 16.7% (95%CI:15.8%-18.0%) were at high risk. In both models, the percentage of high ASCVD risk was higher for participants who were older, men, less educated, current smokers, drinkers and manual workers. Among high-risk individuals, almost all participants (PCEs:90.5%; China-PAR:98.6%) had at least one risk factor; hypertension being the most prevalent. The concordance between PCEs and China-PAR was moderate (kappa:0.428, 95%CI: 0.420-0.434) with a better agreement for women (kappa:0.503,95%CI: 0.493-0.513) than for men (kappa:0.211,95%CI: 0.201-0.221). CONCLUSION: The proportion of participants with a 10-year ASCVD high risk predicted by China-PAR was lower than the results of the PCEs. The risk stratifications of the two algorithms were inconsistent in terms of demographic and life-behaviour characteristics.

Assessing Individual Risk for High-Risk Early Colorectal Neoplasm for Pre-Selection of Screening in Shanghai, China: A Population-Based Nested Case-Control Study.

OBJECTIVE: To identify people with high-risk early colorectal neoplasm is highly desirable for pre-selection in colorectal cancer (CRC) screening in low-resource countries. We aim to build and validate a risk-based model so as to improve compliance and increase the benefits of screening. PATIENTS AND METHODS: Using data from the Shanghai CRC screening cohort, we conducted a population-based nested case-control study to build a risk-based model. Cases of early colorectal neoplasm were extracted as colorectal adenomas and stage 0-I CRC. Each case was matched with five individuals without neoplasm (controls) by the screening site and year of enrollment. Cases and controls were then randomly divided into two groups, with two thirds for building the risk prediction model and the other one third for model validation. Known risk factors were included for risk prediction models using logistic regressions. The area under the receiver operating characteristic curve (AUC) and Hosmer-Lemeshow chi-square statistics were used to evaluate model discrimination and calibration. The predicted individual risk probability was calculated under the risk regression equation. RESULTS: The model incorporating age, sex, family history and lifestyle factors including body mass index (BMI), smoking status, alcohol, regular moderate-to-intensity physical activity showed good calibration and discrimination. When the risk cutoff threshold was defined as 17%, the sensitivity and specificity of the model were 63.99% and 53.82%, respectively. The validation data analysis also showed well discrimination. CONCLUSION: A risk prediction model combining personal and lifestyle factors was developed and validated for high-risk early colorectal neoplasm among the Chinese population. This risk-based model could improve the pre-selection for screening and contribute a lot to efficient population-based screening in low-resource countries.

Cohort profile: protocol and baseline survey for the Shanghai Suburban Adult Cohort and Biobank (SSACB) study.

PURPOSE: The Shanghai Suburban Adult Cohort and Biobank (SSACB) was established to identify environmental, lifestyle and genetic risk factors for non-communicable chronic diseases (NCDs) in adults (20-74 years old) living in a suburban area of Shanghai with rapid urbanisation. PARTICIPANTS: Two of eight suburban district were purposely selected according to participant willingness, health service facilities, population, geographic region and electronic medical record system. From these suburban districts, four communities were selected based on economic level and population size. At stage three, one-third of the committees/villages were randomly selected from each community. All residents aged 20-74 years old were invited as study participants. FINDINGS TO DATE: The baseline data on demographics, lifestyle and physical health-related factors were collected using a face-to-face questionnaire interview. All participants completed physical examinations and had blood and urine tests. Blood and urine samples from these tests were stored in a biobank. From 6 April 2016 through 31 October 2017, we conducted face-to-face interviews and clinical examinations in 44 887 participants: 35 727 from Songjiang District and 9160 from Jiading District. The average age of participants was 56.4±11.2 years in Songjiang and 56.6±10.5 years in Jiading. The prevalence of hypertension, diabetes and dyslipidaemia was 34.0%, 8.2% and 11.1%, respectively. FUTURE PLANS: In-person surveys will be conducted every 5 years. For annual tracking, baseline data was linked to the local health information system, which was composed of an electronic medical record system, a chronic disease management system, a cancer registry system, an infectious disease report system and a death registry system. The data of the SSACB cohort is located in the School of Public Health, Fudan University. International and domestic collaborative research projects are encouraged and inherent in the project.

Sleep quality of Shanghai residents: population-based cross-sectional study.

OBJECTIVE: To estimate the prevalence of poor sleep and its risk factors for adults living in a suburban area of Shanghai with rapid urbanization. METHODS: A total of 37,545 residents who were aged 20 to 74 years and from the "Peak Program," a community-based natural population cohort study, were included. Data on demographics, lifestyle, and physical health-related factors were collected using a face-to-face questionnaire interview. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), and poor sleep was defined as a PSQI score above 7. RESULTS: The overall mean of PSQI score was 3.69 ± 2.57 while the prevalence of poor sleep was 8.3%. The prevalence of poor sleep quality was higher in participants who were older than 40 years, had less education, smoked tobacco, had anxiety, and had a chronic disease (p < 0.05 for all comparisons). After adjustment for confounding, a logistic regression model indicated that poor sleep was associated with advanced age, smoking, anxiety, cardiovascular and cerebrovascular diseases, respiratory diseases, and other chronic diseases (p < 0.05 for all comparisons). In addition, compared to women who were premenopausal, the naturally postmenopausal women (OR 1.675, 95% CI 1.44-1.94) and induced menopausal women (OR 2.26, 95% CI 1.81-2.82) were more likely to report poor sleep. CONCLUSION: The prevalence of poor sleep among individuals who lived in the Songjiang District of Shanghai and were aged 20 to 74 years was remarkably lower than in the general population of China. Poor sleep was generally more common in middle-aged and elderly residents and in those suffering from anxiety and chronic diseases. Regular exercise, anxiety relieving, and treatment improvement of different chronic diseases may help sleep better.

Dihydroartemisinin inhibits the growth and invasion of gastric cancer cells by regulating cyclin D1-CDK4-Rb signaling.

BACKGROUND: Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has a broad range of biological properties, including antitumor activity. However, the mechanisms by which DHA affects the tumorigenesis of gastric carcinoma (GC) are poorly understood. MATERIAL AND METHODS: The targets of DHA were identified by network pharmacology, and the association of CDK4 with clinicopathological characteristics and prognosis in patients with GC was analyzed by using TCGA data. CCK8, Transwell and flow cytometric analyses, as well as a tumor xenograft model, were used to assess the effects of DHA on the growth and migration of GC cells. qRT-PCR and Western blot analyses were used to determine the effects of DHA on the cyclin D1-CDK4-Rb signaling pathway. RESULTS: We identified 13 DHA targets and measured their expression of whichCDK4 expression levels were substantially higher in GC tissues than those in adjacent normal tissues, and high CDK4 expression acted as an independent prognostic factor of poor survival in patients with GC. DHA suppressed cell proliferation, migration and invasion in vitro and in vivo and induced G1 phase cell cycle arrest in a dose-dependent manner by regulating cyclin D1-CDK4-Rb signaling. CONCLUSIONS: DHA inhibits the tumorigenesis and invasion of GC by regulating cyclin D1-CDK4-Rb signaling and may provide therapeutic strategies for the treatment of GC.

Prevalence of tobacco related chronic diseases and its role in smoking cessation among smokers in a rural area of Shanghai, China: a cross sectional study.

BACKGROUND: Tobacco smoking is a recognized risk factor for many chronic diseases and previous study evidences have indicated that smokers receive smoking cessation service after the diagnosis of chronic diseases increases successful rate in quitting. But the prevalence of tobacco related chronic diseases (TCD) among smokers, as well as the role of TCD diagnosis in smoking cessation is still unclear in China. METHODS: From June 2016 to December 2017, we sampled 36, 698 residents aged over 18 years by a three stage sampling in Songjiang district, Shanghai. We conducted a cross-sectional study to understand the prevalence of TCD among smokers, and the role of TCD diagnosis in smoking cessation among ex-smokers as well as the smoking cessation attempt among current smokers. RESULTS: Over all, the prevalence of current smoking is 19.78% (48.36% for male and 0.22% for female). 15.93% of smokers have stopped smoking successfully (1, 376/8, 636). The prevalence of ten selected TCDs among smokers range from 0.63% (Chronic Obstructive Pulmonary Disease, COPD) to 36.31% (hypertension). All of 1, 376 ex-smokers had at least one kind of TCD, and 52.33% of them stop smoking after the diagnosis of TCD, the time interval between TCD diagnosis and smoking cessation ranges from 0 to 65 years, with a median of 9 years. Smokers with TCD had higher prevalence of quit smoking, and current smokers with TCD had higher smoking cessation attempt proportion. CONCLUSIONS: The prevalence of current smoking is still very high among male residents in rural area of Shanghai, and the occurrence of TCD even non-lethal one could provide an opportunity for doctors to assist the smoking cessation among smokers.

Lung cancer incidence in female rises significantly in urban sprawl of Shanghai after introduction of LDCT screening.

OBJECTIVES: LDCT screening for lung cancer has been widely used in China since the release of the NLST trial data in 2011, but little is known about its impact on the incidence and mortality rates of lung cancer in China. METHODS: Official cancer registry data of lung cancer incidence and mortality were collected by Shanghai Municipal Center for Disease Control and Prevention from 2005 to 2014. Two districts (Xuhui and Songjiang Districts) were selected to represent populations with different levels of accessibility to LDCT. Incidence and mortality age-standardized rates (ASRs) were calculated using the Segi/Doll 1960 world standard population. Trends in lung cancer incidence and mortality rate over time, the average annual percent change (APC) and the corresponding 95% confidence interval (CI) were calculated using Joinpoint. RESULTS: In Shanghai, lung cancer incidence rate in men did not change significantly between 2005 and 2014 (APC = 0.76%; 95% CI: -0.27%, 1.80%; P = 0.127); while lung cancer incidence in women increased significantly (APC: 5.50%; 95% CI: 2.94%, 8.13%; P = 0.001). In Xuhui district, where eight tertiary hospitals was located, including Shanghai Cancer Center and Shanghai Chest Hospital, both of which provided LDCT lung cancer screening for eligible patients, the incidence rate of lung cancer increased significantly in women only since 2011(APC: 19.84%, P < 0.001). Overall mortality rate of lung cancer showed a significantly decreasing trend from 2005 to 2014 in men (APC = -2.68%, P = 0.009) but not in women (APC = -0.91%, P = 0.305). In Songjiang district, where limited access to LDCT was provided, lung cancer incidence in women increased significantly between 2005 and 2014 (APC: 5.42%, P = 0.001). Lung cancer incidence rates did not change significantly in men in either district from 2005 to 2014. Mortality rate of lung cancer did not change significantly from 2005 to 2014 in both men (APC = -0.51%, P = 0.259) and women (APC = -1.46%, P = 0.186). CONCLUSION: There is a steady increase in the incidence of lung cancer in women, especially after the wide use of LDCT screening, but without a clear mortality reduction.

Evaluation of a novel fluorescent nanobeacon for targeted imaging of Thomsen-Friedenreich associated colorectal cancer.

The Thomsen-Friedenreich (TF) antigen represents a prognostic biomarker of colorectal carcinoma. Here, using a nanobeacon, the surface of which was fabricated with peanut agglutinin as TF-binding molecules, we demonstrate that the nanobeacon is able to detect TF antigen in frozen and freshly biopsied polyps using fluorescence microscopy. Our results provide important clues about how to detect aberrant colonic tissues in the most timely fashion. Given the versatile application method for this topical nanobeacon, the protocol used in this work is amenable to clinical colonoscopy. Moreover, the prospects of clinical translation of this technology are evident.

The Joint Effects of Lifestyle Factors and Comorbidities on the Risk of Colorectal Cancer: A Large Chinese Retrospective Case-Control Study.

BACKGROUND: Colorectal cancer (CRC) is a major cause of cancer morbidity and mortality. In previous epidemiologic studies, the respective correlation between lifestyle factors and comorbidity and CRC has been extensively studied. However, little is known about their joint effects on CRC. METHODS: We conducted a retrospective case-control study of 1,144 diagnosed CRC patients and 60,549 community controls. A structured questionnaire was administered to the participants about their socio-demographic factors, anthropometric measures, comorbidity history and lifestyle factors. Logistic regression model was used to calculate the odds ratio (ORs) and 95% confidence intervals (95%CIs) for each factor. According to the results from logistic regression model, we further developed healthy lifestyle index (HLI) and comorbidity history index (CHI) to investigate their independent and joint effects on CRC risk. RESULTS: Four lifestyle factors (including physical activities, sleep, red meat and vegetable consumption) and four types of comorbidity (including diabetes, hyperlipidemia, history of inflammatory bowel disease and polyps) were found to be independently associated with the risk of CRC in multivariant logistic regression model. Intriguingly, their combined pattern- HLI and CHI demonstrated significant correlation with CRC risk independently (ORHLI: 3.91, 95%CI: 3.13-4.88; ORCHI: 2.49, 95%CI: 2.11-2.93) and jointly (OR: 10.33, 95%CI: 6.59-16.18). CONCLUSIONS: There are synergistic effects of lifestyle factors and comorbidity on the risk of colorectal cancer in the Chinese population.

Mortality rates and the causes of death related to diabetes mellitus in Shanghai Songjiang District: an 11-year retrospective analysis of death certificates.

BACKGROUND: China is one of the countries with the highest prevalence of diabetes in the world. We analysed all the death certificates mentioning diabetes from 2002 to 2012 in Songjiang District of Shanghai to estimate morality rates and examine cause of death patterns. METHODS: Mortality data of 2654 diabetics were collected from the database of local CDC. The data set comprises all causes of death, contributing causes and the underlying cause, thereby the mortality rates of diabetes and its specified complications were analysed. RESULTS: The leading underlying causes of death were various cardiovascular diseases (CVD), which collectively accounted for about 30% of the collected death certificates. Diabetes was determined as the underlying cause of death on 28.7%. The trends in mortality showed that the diabetes related death rate increased about 1.78 fold in the total population during the 11-year period, and the death rate of diabetes and CVD comorbidity increased 2.66 fold. In all the diabetes related deaths, the proportion of people dying of ischaemic heart disease or cerebrovascular disease increased from 18.0% in 2002 to 30.5% in 2012. But the proportions attributed directly to diabetes showed a downtrend, from 46.7-22.0%. CONCLUSIONS: The increasing diabetes related mortality could be chiefly due to the expanding prevalence of CVD, but has nothing to do with diabetes as the underlying cause. Policy makers should pay more attention to primary prevention of diabetes and on the prevention of cardiovascular complications to reduce the burden of diabetes on survival.