Race/Ethnicity and Mammographic Density: Genetic and Lifestyle Factors

描述（由申请人提供）：这个指导职业发展奖的主要目标是为候选人提供过渡到独立调查员所需的培训和技能发展。将在以下领域获得指导培训：1）癌症风险的替代和中间标志物; 2）分子和遗传流行病学以及群体遗传学的统计方法; 3）生物标本的收集和使用。这个指导培训和研究计划的预期结果是在奖励期的第四年提交R 01申请。乳腺摄影密度（MD）是乳腺癌的一个强有力的危险因素，但目前尚不清楚黑人，西班牙裔和白色女性之间的差异程度，密度如何随时间变化，这种轨迹是否因种族/民族而异，以及哪些基因导致黑人和西班牙裔女性的乳腺摄影密度。我们建议研究乳腺摄影密度和密度变化的种族/民族模式，探索早期和成年MD和密度变化的预测因子，并调查与白色女性密度百分比相关的SNP是否与黑人和西班牙裔女性相似。我们的研究人群是波士顿乳房X线摄影队列研究（BMCS）。BMCS是一项在马萨诸塞州波士顿的布里格姆妇女医院（BWH）接受乳房X光检查的妇女中进行的乳房X光密度研究。自2007年以来，已有2 500多名妇女注册，注册工作仍在进行中。我们预计在研究开始前将再招募约500名女性。女性在入组时完成了一份关于乳腺癌风险因素的问卷，作为本研究的一部分，我们将要求她们完成一份随访问卷，以更新其暴露情况。对于每一位女性，我们已经收集或将收集作为BWH患者收到的所有数字乳房X光照片。MD使用VolparaTM软件进行评估，该软件可计算密度百分比、绝对致密体积和绝对非致密体积的自动体积测量值。我们将尝试从队列中的所有自我确认的黑人（n=295）和西班牙裔（n=340）女性中收集唾液。从收集的唾液中提取的DNA将进行基因分型。我们预计，拟议的研究领域将提供：重要的洞察种族模式的乳房X线摄影密度，新的信息，随着时间的推移，在不同种族/民族群体的密度变化，和多种族的数据，新的措施，MD和目标，为未来精细映射的MD风险等位基因在黑人和西班牙裔妇女。

DESCRIPTION (provided by applicant): The primary goal of this mentored career development award is to provide the candidate with training and skills development needed to transition to an independent investigator. Mentored training will be obtained in the following areas: 1) surrogate and intermediate markers of cancer risk; 2) molecular and genetic epidemiology and statistical methods for population genetics; 3) biospecimen collection and use. The anticipated result of this mentored training and research program is the submission of an R01 application in year four of the award period. Mammographic density (MD) is a strong risk factor for breast cancer, yet it remains unclear the extent to which it differs between black, Hispanic and white women, how density changes over time and whether this trajectory differs by race/ethnicity, and what genes contribute to mammographic density in black and Hispanic women. We propose to examine the racial/ethnic patterns of mammographic density and change in density, explore early-life and adult predictors of MD and change in density, and investigate whether SNPs associated with percent density in white women are similarly associated among black and Hispanic women. Our study population is the Boston Mammography Cohort Study (BMCS). BMCS is a study of mammographic density among women obtaining mammograms at Brigham and Women's Hospital (BWH) in Boston, MA. Over 2500 women have been enrolled since 2007 and enrollment is ongoing. We anticipate that an additional ~500 women will be enrolled prior to the start of the study period. Women completed a questionnaire on breast cancer risk factors at enrollment and as a part of this study we will request that they complete a follow-up questionnaire to update their exposures. For each woman, we have collected, or will collect, all digital mammograms received as a patient at BWH. MD is assessed using VolparaTM software that calculates automated volumetric measures of percent density, absolute dense volume and absolute non-dense volume. We will attempt to collect saliva from all self-identified black (n=295) and Hispanic (n=340) women in the cohort. DNA extracted from collected saliva will be genotyped. We expect that the proposed area of research will provide: important insight into racial patterns of mammographic density, novel information about changes in density over time across racial/ethnic groups, and multiethnic data on novel measures of MD, and targets for future fine mapping of MD risk alleles in black and Hispanic women.