Estimation of cancer incidence and mortality attributable to alcohol drinking in china

Background. Cancer constitutes a serious burden of disease worldwide and has become the second leading cause of death in China. Alcohol consumption is causally associated with the increased risk of certain cancers. Due to the current lack of data and the imperative need to guide policymakers on issues of cancer prevention and control, we aim to estimate the role of alcohol on the cancer burden in China in 2005. Methods. We calculated the proportion of cancers attributable to alcohol use to estimate the burden of alcohol-related cancer. The population attributable fraction was calculated based on the assumption of no alcohol drinking. Data on alcohol drinking prevalence were from two large-scale national surveys of representative samples of the Chinese population. Data on relative risk were obtained from meta-analyses and large-scale studies. Results. We found that a total of 78,881 cancer deaths were attributable to alcohol drinking in China in 2005, representing 4.40% of all cancers (6.69% in men, 0.42% in women). The corresponding figure for cancer incidence was 93,596 cases (3.63% of all cancer cases). Liver cancer was the main alcohol-related cancer, contributing more than 60% of alcohol-related cancers. Conclusions. Particular attention needs to be paid to the harm of alcohol as well as its potential benefits when making public health recommendations on alcohol drinking. \ua9 2010 Liang et al; licensee BioMed Central Ltd

The Level of the Transcription Factor Pax6 Is Essential for Controlling the Balance between Neural Stem Cell Self-Renewal and Neurogenesis

Neural stem cell self-renewal, neurogenesis, and cell fate determination are processes that control the generation of specific classes of neurons at the correct place and time. The transcription factor Pax6 is essential for neural stem cell proliferation, multipotency, and neurogenesis in many regions of the central nervous system, including the cerebral cortex. We used Pax6 as an entry point to define the cellular networks controlling neural stem cell self-renewal and neurogenesis in stem cells of the developing mouse cerebral cortex. We identified the genomic binding locations of Pax6 in neocortical stem cells during normal development and ascertained the functional significance of genes that we found to be regulated by Pax6, finding that Pax6 positively and directly regulates cohorts of genes that promote neural stem cell self-renewal, basal progenitor cell genesis, and neurogenesis. Notably, we defined a core network regulating neocortical stem cell decision-making in which Pax6 interacts with three other regulators of neurogenesis, Neurog2, Ascl1, and Hes1. Analyses of the biological function of Pax6 in neural stem cells through phenotypic analyses of Pax6 gain- and loss-of-function mutant cortices demonstrated that the Pax6-regulated networks operating in neural stem cells are highly dosage sensitive. Increasing Pax6 levels drives the system towards neurogenesis and basal progenitor cell genesis by increasing expression of a cohort of basal progenitor cell determinants, including the key transcription factor Eomes/Tbr2, and thus towards neurogenesis at the expense of self-renewal. Removing Pax6 reduces cortical stem cell self-renewal by decreasing expression of key cell cycle regulators, resulting in excess early neurogenesis. We find that the relative levels of Pax6, Hes1, and Neurog2 are key determinants of a dynamic network that controls whether neural stem cells self-renew, generate cortical neurons, or generate basal progenitor cells, a mechanism that has marked parallels with the transcriptional control of embryonic stem cell self-renewal

Relationship between cancer mortality/incidence and ambient ultraviolet B irradiance in China

Background: Studies finding an inverse correlation of ambient solar irradiance with cancer mortality were the first to suggest that sun exposure and probably, therefore, vitamin D might protect against some cancers. Such correlation has been shown in Asian populations in some studies. We analyzed the correlation between mortality and incidence from a number of cancers and ambient solar ultraviolet (UV) B irradiance in China. Methods: Cancer mortality data were obtained from the Second National Death Survey conducted in a sample of 263 counties in China from 1990 to 1992. National cancer registration data 1998-2002 in China were used for estimation of cancer incidence. Satellite measurements of cloud-adjusted ambient UVB intensity at 305 nm were obtained from a NASA database and GIS methods used to estimate the average daily irradiance for the 263 counties in 1990. We estimated cancer mortality rate ratios per 10 mW/(nm m2) change in UVB by fitting a negative binomial regression model with mortality as the response variable and UVB as the independent variable, adjusted for sex, age, and urban or rural area. Results: Mortality rates for all cancers and cancers of the esophagus, stomach, colon and rectum, liver, lung, breast, and bladder were inversely correlated with ambient UVB. This correlation was present in men and women and rural residents for all these cancers but not urban residents for cancers of the esophagus, colon and rectum and liver. Lung cancer mortality showed the strongest inverse correlation with an estimated 12% fall per 10 mW/(nm m2) increase in UVB irradiance even if adjusted for smoking. Only incidence rates for cancers of the esophagus, stomach, colon and rectum and cervix were inversely correlated with ambient UVB. Mortality and incidence from nasopharyngeal cancer increased with increasing UVB [respectively 27 and 12% per mW/(nm m2)]. Mortality from cancer of the cervix also increased, but to a lesser extent and mortality from leukemia was not consistently correlated with UVB irradiance. Conclusion: Mortality from all cancers together and most major cancers in China was inversely associated with solar UVB. These associations were similar to those observed in a number of populations of European origin. Incidence of some cancer types had the same correlation with UVB. They suggest the possibility that vitamin D may reduce the incidence or improve the outcome of cancer in Chinese people

Potential Autoregulation of Transcription Factor PU.1 by an Upstream Regulatory Element

Regulation of the hematopoietic transcription factor PU.1 (Spi-1) plays a critical role in the development of white cells, and abnormal expression of PU.1 can lead to leukemia. We previously reported that the PU.1 promoter cannot induce expression of a reporter gene in vivo, and cell-type-specific expression of PU.1 in stable lines was conferred by a 3.4-kb DNA fragment including a DNase I hypersensitive site located 14 kb upstream of the transcription start site. Here we demonstrate that this kb −14 site confers lineage-specific reporter gene expression in vivo. This kb −14 upstream regulatory element contains two 300-bp regions which are highly conserved in five mammalian species. In Friend virus-induced erythroleukemia, the spleen focus-forming virus integrates into the PU.1 locus between these two conserved regions. DNA binding experiments demonstrated that PU.1 itself and Elf-1 bind to a highly conserved site within the proximal homologous region in vivo. A mutation of this site abolishing binding of PU.1 and Elf-1 led to a marked decrease in the ability of this upstream element to direct activity of reporter gene in myelomonocytic cell lines. These data suggest that a potential positive autoregulatory loop mediated through an upstream regulatory element is essential for proper PU.1 gene expression