中国乳腺癌专病队列研究：泛共享生物样本库的建设与进展

目的 生物样本库建设在疾病的精准预防、诊治研究中发挥着不可替代的作用，基于大人群队列的可共享生物样本库网络是未来发展方向。本研究的生物样本库是国家精准医学计划“中国乳腺癌专病队列研究”的重点内容之一，旨在解决标准化程度不足、共享性不够的瓶颈。方法 通过建设“实体库-信息库-延伸库”、泛共享的乳腺癌专病队列生物样本库网络以及建立严格的标准制定与质量控制标准建设标准化生物样本库。结果 生物样本库为乳腺癌风险评估、预测预警、早期筛查、分型分类、个体化治疗、疗效和安全性预测及监控等精准防治诊治方案和临床决策系统研究提供可共享的生物样本库资源。结论 生物样本库资料细化完整，病例样本量充足，可满足医疗大数据、基因组学、代谢组学和表观遗传学等多个领域的研究需要。     

中国乳腺癌专病队列研究：人群队列研究方法及基线特征

目的 乳腺癌在女性癌症中发病率第一且逐年上升。2016年9月,国家重点研发计划精准医学研究中国乳腺癌专病队列项目启动,旨在整合队列资源、提高随访质量、构建标准共享的乳腺癌专病队列,为实现乳腺癌发现、预防、早诊、治疗及预后研判等提供研究基础与标准化数据共享平台。方法 本研究基于社区人群,采用询问调查、身体测量、生物样本采集、乳腺超声和钼靶X线检查建立前瞻性队列,采用区域健康监测和定向监测随访队列。结果 整合乳腺癌专病社区人群队列112 118人,其中完成55 419人标准化队列调查,54 304人采集生物样本。平均年龄51.7岁,超重/肥胖女性占62.7%,绝经女性占48.9%。结论 本研究将为中国女性乳腺癌精准防治提供队列基础和研究平台。     

呼吸系统疾病专病队列研究的标准制定与数据共享

目的 慢性阻塞性肺疾病、哮喘、间质性肺疾病和肺血栓栓塞症是重大呼吸系统疾病,严重危害我国居民健康,整合并开展大规模人群队列研究有助于观察疾病的暴露、发病与转归情况。本研究针对我国社区与临床队列资源的多源异构现状,制定呼吸系统疾病专病队列（呼吸专病队列）数据标准,为解决多源异构数据所致共享障碍,以及项目最大程度开展数据交换、整合、共享、储存与利用提供思路与方法。方法 呼吸专病队列数据标准制定思路：①学习、参考国际标准,包括临床数据交换标准协会（CDISC）的CDASH模型,观察性医疗结果合作组织（OMOP）的CDM通用数据模型;②整理、归纳所纳入的4个呼吸专病队列资源,评估各队列资源间的同质性与整合的可能性;③专家讨论,建立呼吸专病队列数据标准。结果 研究纳入的现有呼吸专病队列变量模块同质性较好,基本结构相似,具有数据整合的可行性。参考国际标准,经专家讨论,项目组构建呼吸专病队列的数据标准概念框架,由呼吸专病队列通用数据标准及疾病特异数据标准两部分构成,其中通用数据标准针对各专病队列中均有涉及、能够统一标准的问题或研究变量;特异数据标准则为各疾病特有的问题。经映射匹配,认为该标准与各现有专病队列的变量模块匹配良好,标准可行。结论 数据标准建立后,在回顾性整合现有队列资源的同时,使不同项目以相同的定义和标准开展长期随访,收集核心数据集,为未来开展多中心研究扫除因数据标准不一导致的数据共享障碍,更有利于多源的整合与共享。     

孤独症谱系障碍队列研究进展的概括性评价

目的 了解孤独症谱系障碍（ASD）队列研究现状,探讨基于真实世界数据（RWD）构建ASD专病队列的可行性。方法 检索、筛选主要中英文数据库中截至2022年12月发表的ASD队列研究,归纳ASD队列研究特点。结果 共纳入ASD队列研究1 702篇,我国仅有60项（3.53%）。筛选出ASD相关队列163个,其中55.83%为出生队列,28.22%为ASD专病队列,4.91%为ASD高危人群队列;多数队列利用医院注册登记等RWD或开展社区现场调查获取研究对象信息,并通过量表或临床诊断确认ASD患者。研究内容包括ASD发生及预后相关危险因素研究、ASD共病模式研究及ASD对自身其他健康状况和对子代健康影响的研究。结论 目前发达国家ASD队列研究全面丰富,我国仍处于起步阶段。RWD为ASD专病队列构建提供了数据基础,也带来了研究的新机遇,但仍需开展病例验证等工作保证队列建设的科学性。     

华西职业性尘肺病队列研究设计及初步结果

尘肺病是影响我国职业人群健康最主要的职业性肺部疾病,其预防、诊断、治疗和康复尚缺乏系统性的研究,国内外开展的尘肺队列研究多以接尘作为观察起点,以发病或死亡作为结局,缺乏精细化的尘肺病临床队列研究。本课题以国家临床重点专科职业病科为依托,建立华西职业性尘肺病专病队列,以循证医学证据为基础,通过专家论证建立尘肺病队列入组标准,招募尘肺病患者入组,并开展长期随访,收集入组对象的基线信息、职业暴露信息、诊疗信息,同时采集血液、肺灌洗液等生物样本,在此基础上搭建尘肺病队列多模态数据动态采集及管理信息系统。根据大型人群队列终点事件长期随访技术规范,数据安全及数据处理技术规范,中国人类遗传资源管理要求,对队列观察对象开展连续、规范地追踪随访,为尘肺病发病、诊疗及预后的系统性多组学多模态研究提供支撑。精细化的华西职业性尘肺队列还将为尘肺纤维化机制的深入研究、靶向药物开发及尘肺病的精准诊疗提供研究平台。本文主要针对华西职业性尘肺病队列的研究设计和初步结果做简要介绍。     

肺癌社区高危人群队列研究进展

肺癌社区高危人群队列是2017年启动的国家重点研发计划精准医学专项"肺癌专病队列研究"的一部分，其主要目标是在全国7个大区的7个城市，收集5万例以上社区人群肺癌危险因素暴露信息，识别肺癌高危人群，开展低剂量螺旋CT筛查，并进一步追踪肺癌确诊和死亡信息；同时采集生物样本，建立以社区人群为基础、涵盖危险因素暴露、人群危险评估、低剂量螺旋CT筛查、生物样本以及结局随访信息的肺癌社区高危人群队列，为后续开展肺癌精准医学研究提供数据和样本支持。     

亚欧地区部分国家队列研究进展分析

目的 梳理西亚地区17个国家和中东欧地区16个国家队列研究概况,分析典型前瞻性自然人群队列的分布、建设及发展状况。方法 采用文献回顾法收集队列研究的基本信息,采用描述性研究方法分析队列研究的特征。结果 西亚和中东欧地区各国共有样本量在1 000人及以上的队列研究562项,国家内队列研究468项（83.27%）,国际多中心队列研究94项（16.73%）;从研究性质来看,病因学研究347项（61.74%）;从研究内容来看,慢性非传染性疾病研究310项（55.16%）,母婴健康研究125项（22.24%）,其中,慢性非传染性疾病研究中,癌症研究51项（16.45%）,心血管疾病研究83项（26.77%）;共有大型前瞻性自然人群队列研究10项,主要分布在伊朗和欧洲地区各国,均为在研项目,持续时间在8～29年之间,队列规模>50 000人的4项;从建立机制看,均进行流行病学调查、健康体检和生物样本收集;从队列发展来看,10项队列研究中有9项在建设初期发表文章较少,随后逐年增长并保持在一定水平上下波动。结论 西亚和中东欧地区各国队列研究地区分布不平衡,主要进行病因学研究,重点关注癌症、心血管疾病、糖尿病、呼吸系统疾病、精神心理疾病等慢性非传染性疾病和母婴健康,具有少数可供借鉴的大型前瞻性自然人群队列。     

中国海南百岁老人队列研究:研究设计及初步结果

目的 调查海南百岁老年人群的健康状况、功能状态、精神心理、卫生需求等其他长寿相关的流行病学特征及其主要影响因素,以探讨长寿及衰老的自然历程及相关机制。方法 中国海南百岁老人队列研究（CHCCS）是一项基于社区人群,具有问卷信息、身体测量、生物标本、临床影像等数据库和生物样本资料的全省百岁老人全样本的前瞻性队列研究。2014-2017年为基线调查,根据海南省民政部门提供的百岁老人户籍信息,对全省18市（县）百岁老人和5市（县）高龄对照老人进行入户调查,调查内容主要包括问卷访谈、体格检查和生物标本采集。计划每2年随访1次其患病与生存现状。结果 在海南省民政部门2014年提供的百岁老人名单中,1 473位百岁老人健在并可取得联系。截至2016年12月,其中的268人去世,203人拒访,1 002位百岁老人同意参加本研究。本文对海南百岁老人队列2014-2016年完成调查且资料完整的722例百岁老人的基线数据进行了初步分析,其平均年龄为（102.7±2.7）岁,女性占83.0%、丧偶占88.8%、汉族占84.5%、与家人同居者占87.8%、文盲占89.7%、农民占81.0%。结论 CHCCS将提供我国及亚洲最大样本的长寿人群的数据资料,并抢救性采集其珍稀的生物样本资源,为我国长寿、衰老及健康老龄化研究提供多学科交叉的技术平台和研究基地。     

东风-同济队列研究:研究方法及调查对象基线和第一次随访特征

目的 探讨环境、职业因素、个人生活方式、遗传因素和遗传-环境交互作用对某职业人群的主要慢性病发生和发展的影响。方法 东风-同济队列研究为一项建立有生物样本库的前瞻性开放式队列研究。2008-2009年对湖北省十堰市东风汽车公司退休职工进行基线调查,包括问卷调查、体格检查、生化指标检查和血液样本采集。计划每5年随访一次。2013年4-10月完成了第一次随访,再次进行了问卷调查、体格检查、生化指标检查和血液样本采集。结果 基线调查共邀请了31000名东风汽车公司退休职工,其中27009名(占87%)退休职工同意参加并提供了流行病学调查信息和基线血液样本。东风-同济队列研究入选人群的基线平均年龄为63.6岁,其中男性占44.6%。2013年第一次随访共纳入了38295名退休职工,男性占44.7%。在2013年第一次随访研究人群中,40.5%的参与者为高中及以上学历。队列人群男性和女性的现在吸烟率分别为33.6%和2.0%,饮酒率分别为39.9%和10.6%;38295人群中流行病学调查自我报告的慢性疾病患病率分别为高血压41.1%、高脂血症24.3%、糖尿病13.9%、冠心病16.7%、中风5.1%、慢性支气管炎12.7%和哮喘4.0%;男性高血压和中风的自我报告患病率高于女性。2008年基线人群中,共有25978人随访到相关信息,2008年基线人群第一次的随访率为96.2%。结论 东风-同济队列的建立为研究遗传、环境及遗传-环境交互作用对慢性病发生和发展提供了重要资源。     

中国慢性病前瞻性研究:研究方法和调查对象的基线特征

目的 探讨环境、个体生活方式、体格和生化指标以及遗传易感性等因素对中国成年人主要慢性病发生、发展的影响.方法 中国慢性病前瞻性研究为一项建立有生物样本库的超大型前瞻性队列研究.2004-2008年在城市和农村各5个地区开展基线调查,包括问卷调查、体格检查和血液样本采集.2008年对随机抽取5％的队列成员进行第一次重复调查.通过常规和定向监测对队列成员进行长期全死因监测和四类主要慢性病的发病监测,并从全民医疗保险数据库获取个体全病种入院诊疗信息.结果 基线调查共入选30～79(平均51.5)岁512 891名对象.其中男性占41.0％,农村人群占55.9％.队列人群男女性现在吸烟率分别为61.3％和2.4％;男性过去一年中每周至少一次饮酒率为33.4％,女性为2.1％;超重肥胖(BMI≥24.0 kg/m2)率,男性为41.8％,女性为45.3％;调查时SBP≥140 mm Hg或DBP≥90 mm Hg(1 mm Hg=1.33 kPa)的比例男性为32.2％,女性为30.2％.不同年龄、性别和地区各主要调查指标均有差异.结论 中国不同地区、年龄、性别及出生年代人群具有不同的慢性病暴露谱.     

A Patient-Level Calibration Framework for Evaluating Surveillance Strategies: A Case Study of Mammographic Follow-Up After Early Breast Cancer

ObjectiveCurrently all women who have completed their primary treatment for early breast cancer are invited to receive routine annual mammography. There is no randomized controlled trial evidence to support this schedule, and model-based analysis is required. This paper describes a novel data collection and model calibration process to analyze the cost-effectiveness of alternative follow-up schedules for early breast cancer survivors.MethodsA discrete event simulation model describes the progression of early breast cancer after the completion of primary treatment, representing impalpable and palpable recurrence and the detection of impalpable disease via follow-up mammography. Retrospective data from the South Australian Cancer Registry and clinical and administrative hospital databases were linked for 407 postmenopausal women diagnosed with moderate-prognosis early breast cancer from 2000 to 2008. These data formed the basis of a patient-level probabilistic calibration process.ResultsFor 50- to 69-year-old survivors, annual follow-up for 5 years, with visits every 2 years thereafter, appears to be cost-effective. For women aged 70 to 79 years at diagnosis, a surveillance schedule similar to general population screening (2 yearly) appears to be most cost-effective if high rates of adherence can be maintained.ConclusionsThis study demonstrated the potential value of combining linked, retrospective data and decision analytic modeling to provide estimates of costs and health outcomes that are sufficiently robust to inform cancer clinical guidelines and individual patient decisions regarding appropriate follow-up schedules.     

What Women Want: Patient Recommendations for Improving Access to Breast and Cervical Cancer Screening and Follow-up

BackgroundThe patient voice remains underrepresented in clinical and public health interventions. To inform interventions that strive to improve access to breast and cervical cancer screening and follow-up among low-income populations, we explored recommendations from low-income women pursuing health care in the safety net.MethodsSemi-structured interviews were conducted among women receiving follow-up care for an abnormal breast or cervical cancer screening result or a positive cancer diagnosis in federally qualified health centers, free clinics, or an academic cancer center in the Chicago metropolitan area.FindingsOf the 138 women interviewed in the parent study, 52 women provided recommendations for improving access to screening and follow-up care. Most were between 41 and 65 years old (62%) and African American (60%) or White (25%). Recommendations included strengthening community-based health education with more urgent messaging, strategic partnerships, and active learning experiences to increase patient engagement, which women regarded as a key driver of access. Women also suggested increasing access by way of changes to health care delivery systems and policy, including more direct patient–provider and patient–clinic communications, addressing delays caused by high patient volume, combining preventive services, expanding insurance coverage, and adjusting screening guidelines.ConclusionsThis exploratory study demonstrates important insights from the patient lens that may help to increase the acceptability and efficacy of community and clinical interventions aimed at improving access to breast and cervical cancer screening and follow-up. Further research is needed to identify appropriate integration of patient input into interventions, practice, and policy change.     

“Whilst you are here…” Acceptability of providing advice about screening and early detection of other cancers as part of the breast cancer screening programme

ObjectivesThis research aimed to assess women''s willingness to receive advice about cervical and bowel cancer screening participation and advice on cancer symptom awareness when attending breast cancer screening.MethodsWomen (n = 322) aged 60–64 years, living in the United Kingdom, who had previously taken part in breast cancer screening were recruited via a market research panel. They completed an online survey assessing willingness to receive advice, the potential impact of advice on breast screening participation, prospective acceptability and preferences for mode and timing of advice.ResultsMost women would be willing to receive information about cervical (86%) and bowel cancer screening (90%) and early symptoms of other cancers (92%) at a breast cancer screening appointment. Those who were not up to date with cervical cancer screening were less willing. Prospective acceptability was high for all three forms of advice and was associated with willingness to receive advice. Women would prefer to receive advice through a leaflet (41%) or discussion with the mammographer (30%) either before the appointment (27%), at the appointment (44%) or with their results (22%).ConclusionsWhile there is high willingness and high acceptability towards using breast cancer screening as a teachable moment for advice about prevention and early detection of other cancers, some women find it unacceptable and this may reduce their likelihood of attending a breast screening appointment.Patient or Public ContributionThis study focused on gaining women''s insights into potential future initiatives to encourage screening and early diagnosis of cancer. Members of the public were also involved in piloting the questionnaire.     

Chocolate Candy and Incident Invasive Cancer Risk in the Women’s Health Initiative: An Observational Prospective Analysis

BackgroundLaboratory and animal studies suggest an inverse association between chocolate consumption and the risk of cancer. Epidemiological studies have yielded inconsistent evidence.ObjectiveTo assess the association of chocolate candy consumption with incident, invasive total, breast, colorectal, and lung cancers in a large cohort of postmenopausal American women.DesignProspective cohort study with a mean 14.8-year follow-up. Chocolate candy intake was assessed by food frequency questionnaire. Invasive cancer events were assessed by physician adjudication.Participants/settingThe Women’s Health Initiative Study enrolled 161,808 postmenopausal women at 40 clinical centers nationwide between 1993 and 1998. Of these women, 114,281 with plausible food frequency or biometric data and no missing data on chocolate candy exposure were selected for analysis.Main outcome measuresCancer risk in quartiles of chocolate candy consumption with the first quartile as referent.Statistical analysesMultivariable Cox regression was used to calculate hazard ratios and 95% confidence intervals.ResultsThere were 16,164 documented incident invasive cancers, representing an incidence rate of 17.0 per 100 participants and 12.3 per 1000 person years during follow-up among participants without any preexisting cancers or missing outcome data. There were no statistically significant associations for total invasive cancer (P-linear = .47, P-curvature = .14), or invasive breast cancer (P-linear = .77, P-curvature = .26). For colorectal cancer P-linear was .02, P-curvature was .03, and compared with women eating a 1 oz (28.4 g) chocolate candy serving <1 time per month, the hazard ratio for ≥1.5 times/wk was 1.18 (95% confidence interval: 1.04-1.35). This result may be attributable to the excess adiposity associated with frequent chocolate candy consumption.ConclusionsIn the Women’s Health Initiative, there was no significant association between chocolate candy consumption and invasive total or breast cancer. There was a modest 18% higher risk of invasive colorectal cancer for women who ate chocolate candy at least 1.5 times/wk. These results require confirmation.     

Hormonal and body-size factors in relation to breast cancer risk: a prospective study of 11,889 women in a low-incidence area

PURPOSE: This prospective cohort study of 11,889 women was conducted to determine significant factors associated with the risk of breast cancer among Chinese women in Taiwan, a low-incidence area. METHODS: In-person interviews were completed for subjects to solicit information on hormonal factors. Measurements of height, weight, and waist-and- hip circumferences were performed by well-trained assistants using standardized techniques. Cox proportional hazards models were employed to estimate relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: During an average follow-up time of 10.3 years (range: 1 to 11 years) with an accumulation of 134,063 person-years, 104 incident breast cancer cases were identified through data linkage with national cancer registry profile. There was a significant elevation in breast-cancer risk with increasing duration of the interval between age at menarche and age at first full-term pregnancy (FFTP). Additionally, central adiposity reflected by hip circumference was a significant predictor of breast cancer in this Chinese female population. CONCLUSIONS: The findings of this study indicated common mechanisms responsible for the higher incidence of breast cancer in Western populations may also explain the risk of breast cancer development in Taiwan, a low-incidence area.     

P.O.W. (Protect Our Women): Results of a Breast Cancer Prevention Project Targeted to Older African-American Women

ABSTRACT

Objective: Encourage older African-American women to participate in breast cancer detection. Breast cancer deaths for older African-American women are higher than for Caucasian counterparts. Effective outreach education about mammography and breast exam is one method to reduce the disparity by encouraging women to enter treatment earlier through earlier diagnosis. Traditional outreach strategies have proven ineffective with this cohort.

Method: In this study we utilized the trust placed in known community leaders to recruit older African-American women to participate in breast health education leading to completion of a mammogram. One hundred sixty-two women were identified as participants.

Results: Seventy-nine percent of the women who completed the project obtained mammograms and 9% had mammograms scheduled at 1-month follow-up, whereas 22% of the individuals who received only mailed educational materials completed mammograms and none had scheduled mammograms pending.

Discussion: Health education for difficult-to-reach populations can be effective but requires greater inclusion of community partners to offset issues related to trust, health beliefs, and access.