Sellers T A, Anderson V E, Potter J D, Bartow S A, Chen P L, Everson L, King R A, Kuni C C, Kushi L H, McGovern P G
Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis 55454-1015, USA.
Genet Epidemiol. 1995;12(4):417-29. doi: 10.1002/gepi.1370120409.
In 1944, a case-control family study was initiated at the Dight Institute for Human Genetics at the University of Minnesota to study the influences of childbearing breastfeeding, and hereditary susceptibility on the occurrence and age-of-onset of breast cancer. Index cases (probands) were women ascertained at the Tumor Clinic of the University of Minnesota Hospital. Medical history and life style information were obtained on probands and relatives, and all cancers were histologically verified. A total of 544 families were studied, with probands diagnosed between 1931 and 1952. All of the records and pathology slides have been maintained from the original study; for most probands this includes the original tissue blocks. We are conducting a historical cohort study of selected of selected first- and second-degree female relatives (sisters, daughters, nieces, granddaughters) of the probands and a group of control women identified as the spouses of all male first- and second-degree relatives (brothers, sons, grandsons, and nephews). The subsequent development of breast cancer is being determined to quantify the absolute risk associated with a positive family history. Current disease status is ascertained with mammography, and stromal density is measured using digital imaging. Segregation analysis will be applied to examine how non-genetic factors such as diet, exogenous hormone use, and body fat distribution influence risk in women at high risk because of family history. A subset of families are being selected for molecular analysis of the BRCA1 gene or for linkage analyses to identify putative susceptibility loci other than BRCA1. Documented cancer histories were known for at least three generations, and the current study extends the pedigrees up to four or five generations for every family, allowing a detailed description of familial risk. This cohort study of breast cancer families is likely to be important in both quantity and quality of data and will serve as a major genetic epidemiologic resource, being free of selection bias and having relevant non-genetic exposure determined in at least four generations.
1944年，明尼苏达大学迪特人类遗传学研究所启动了一项病例对照家系研究，以探讨生育、母乳喂养及遗传易感性对乳腺癌发病及发病年龄的影响。索引病例（先证者）为在明尼苏达大学医院肿瘤门诊确诊的女性。收集了先证者及其亲属的病史和生活方式信息，所有癌症均经组织学证实。共研究了544个家系，先证者于1931年至1952年间确诊。原始研究的所有记录和病理切片均得以保存；对大多数先证者而言，这包括原始组织块。我们正在对先证者的选定的一级和二级女性亲属（姐妹、女儿、侄女、孙女）以及一组被确定为所有男性一级和二级亲属（兄弟、儿子、孙子和侄子）配偶的对照女性进行历史性队列研究。通过确定乳腺癌的后续发病情况来量化与阳性家族史相关的绝对风险。通过乳房X线摄影确定当前疾病状态，并使用数字成像测量基质密度。将应用分离分析来研究饮食、外源性激素使用和体脂分布等非遗传因素如何影响因家族史而处于高风险的女性的患病风险。正在选择一部分家系对BRCA1基因进行分子分析，或进行连锁分析以确定除BRCA1之外的假定易感基因座。至少三代人的癌症病史有记录，当前研究将每个家系的谱系扩展到四或五代，从而能够详细描述家族风险。这项乳腺癌家系队列研究在数据的数量和质量方面可能都很重要，并将成为主要的遗传流行病学资源，不存在选择偏倚，且至少四代人的相关非遗传暴露情况已确定。
