Attributable Causes of Breast Cancer and Ovarian Cancer in China:Reproductive Factors,Oral Contraceptives and Hormone Replacement Therapy

Objective： To provide an evidence-based, consistent assessment of the burden of breast cancer attributable to reproductive factors （RFs, including nulliparity, mean number of children, age at first birth and breastfeeding）, use of oral contraceptives （OCs, restricted to the age group of 15-49 years）, and hormone replacement therapy （HRT）, as well as of the burden of ovarian cancer attributable to the mean number of children in China in 2005. Methods： We derived the prevalence of these risk factors and the relative risk of breast and ovarian cancer from national surveys or large-scale studies conducted in China. In the case of RFs, we compared the exposure distributions in 2001 and counterfactual exposure. Results： Exposure of RFs in 2002 was found to account for 6.74% of breast cancer, corresponding to 9,617 cases and 2,769 deaths, and for 2.78% of ovarian cancer （712 cases, 294 deaths）. The decrease in mean number of children alone was responsible for 1.47% of breast cancer and 2.78% of ovarian cancer. The prevalence of OC use was 1.74% and the population attributable fraction （PAF） of breast cancer was 0.71%, corresponding to 310 cases and 90 deaths. The PAF of breast cancer due to HRT was 0.31%, resulting in 297 cases and 85 deaths. Conclusion： RFs changes in China contributed to a sizable fraction of breast and ovarian cancer incidence and mortality, whereas HRT and OCs accounted for relatively low incidence of breast cancer in China.

Attributable Causes of Cancer in China:Fruit and Vegetable

Objective：To provide an evidence-based and consistent assessment of the burden of cancer attributable to inadequate fruit and vegetable intake in China in 2005.Methods：The proportions of cancers attributable to low consumption of vegetable and fruit were calculated separately to estimate the burden of related cancers for the year 2005 in China.Data on the prevalence of exposure were derived from a Chinese nutrition and health survey.Data on relative risks were mainly derived from meta-analysis.Attributable fractions were calculated based on the counterfactual scenario which was a shift in the exposure distribution.Results：The total cancer burden attributable to inadequate consumption of fruit was up to 233,000 deaths （13.0% of all cancers） and 300,000 cases （11.6% of all cancers） in 2005.Increasing consumption of vegetable to the highest quintile could avoid total cancer deaths and cases by 3.6% （64,000 persons） and 3.4% （88,000 persons）.The contributions to cancer burden were higher in rural areas than in urban areas.They have greater influence on men than on women.The largest proportions of cancer burden attributable to low fruit and vegetable intake were for oral and pharyngeal cancers.Conclusion：This study showed that inadequate intake of fruit and vegetable makes a significant contribution to the cancer burden.Increasing consumption of fruit and vegetable could prevent many cancer deaths and save many lives.Promoting the consumption of fruit and vegetable is an important component in diet-based strategies for preventing cancer.

IFN-γ^(+) cytotoxic CD4^(+) T lymphocytes are involved in thepathogenesis of colitis induced by IL-23 and the foodcolorant Red 40

The food colorant Red 40 is an environmental risk factor for colitis development in mice with increased expression of interleukin(IL)-23.This immune response is mediated by CD4^(+)T cells,but mechanistic insights into how these CD4^(+)T cells trigger andperpetuate colitis have remained elusive.Here,using single-cell transcriptomic analysis,we found that several CD4^(+)T-cell subsetsare present in the intestines of colitic mice,including an interferon(IFN)-γ-producing subset.In vivo challenge of primed mice withRed 40 promoted rapid activation of CD4^(+)T cells and caused marked intestinal epithelial cell(IEC)apoptosis that was attenuated bydepletion of CD4^(+)cells and blockade of IFN-γ.Ex vivo experiments showed that intestinal CD4^(+)T cells from colitic mice directlypromoted apoptosis of IECs and intestinal enteroids.CD4^(+)T cell-mediated cytotoxicity was contact-dependent and required FasL,which promoted caspase-dependent cell death in target IECs.Genetic ablation of IFN-γconstrained IL-23-and Red 40-inducedcolitis development,and blockade of IFN-γinhibited epithelial cell death in vivo.These results advance the understanding of themechanisms regulating colitis development caused by IL-23 and food colorants and identify IFN-γ^(+)cytotoxic CD4^(+)T cells as a newpotential therapeutic target for colitis.

Immune responses elicited by ssRNA(-) oncolytic viruses in the host and in the tumor microenvironment

Oncolytic viruses(OVs)are at the forefront of biologicals for cancer treatment.They represent a diverse landscape of naturally occurring viral strains and genetically modified viruses that,either as single agents or as part of combination therapies,are being evaluated in preclinical and clinical settings.As the field gains momentum,the research on OVs has been shifting efforts to expand our understanding of the complex interplay between the virus,the tumor and the immune system,with the aim of rationally designing more efficient therapeutic interventions.Nowadays,the potential of an OV platform is no longer defined exclusively by the targeted replication and cancer cell killing capacities of the virus,but by its contribution as an immunostimulator,triggering the transformation of the immunosuppressive tumor microenvironment(TME)into a place where innate and adaptive immunity players can efficiently engage and lead the development of tumor-specific long-term memory responses.Here we review the immune mechanisms and host responses induced by ssRNA(-)(negative-sense single-stranded RNA)viruses as OV platforms.We focus on two ssRNA(-)OV candidates:Newcastle disease virus(NDV),an avian paramyxovirus with one of the longest histories of utilization as an OV,and influenza A(IAV)virus,a well-characterized human pathogen with extraordinary immunostimulatory capacities that is steadily advancing as an OV candidate through the development of recombinant IAV attenuated platforms.