Race/Ethnicity and Mammographic Density: Genetic and Lifestyle Factors

描述（由申请人提供）：这个导师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)群体遗传学的分子遗传流行病学和统计方法；3)生物标本的收集和使用。该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R01申请。乳房x光检查密度（MD）是乳腺癌的一个重要危险因素，但目前尚不清楚黑人、西班牙裔和白人女性之间的差异程度，密度如何随时间变化，这种变化轨迹是否因种族/民族而异，以及哪些基因影响了黑人和西班牙裔女性的乳房x光检查密度。我们建议研究乳腺x线摄影密度和密度变化的种族/民族模式，探索早期和成年期MD和密度变化的预测因素，并调查白人女性中与百分比密度相关的snp是否与黑人和西班牙裔女性相似。我们的研究对象是波士顿乳房x线摄影队列研究（BMCS）。BMCS是一项在马萨诸塞州波士顿布里格姆妇女医院（BWH）接受乳房x光检查的妇女的乳房x光密度研究。自2007年以来，已有2500多名妇女注册，注册仍在进行中。我们预计，在研究开始前，将有额外的约500名妇女被纳入研究。女性在入组时完成了一份关于乳腺癌风险因素的调查问卷，作为这项研究的一部分，我们将要求她们完成一份后续调查问卷来更新她们的暴露情况。对于每一位女性，我们已经收集了，或者将要收集，作为BWH患者收到的所有数字乳房x光片。MD的评估使用VolparaTM软件，该软件可以自动计算密度百分比、绝对密集体积和绝对非密集体积的体积测量。我们将尝试收集队列中所有自认为是黑人（n=295）和西班牙裔（n=340）女性的唾液。从收集的唾液中提取的DNA将进行基因分型。我们期望提出的研究领域将提供：对乳房x线摄影密度的种族模式的重要见解，关于不同种族/民族人群密度随时间变化的新信息，关于新的MD测量方法的多种族数据，以及未来黑人和西班牙裔女性MD风险等位基因精细定位的目标。

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.