家族遗传倾向对于发生乳腺浸润癌特定组织学亚型的影响尚不明确。
2019年5月23日，美国癌症学会《癌症》在线发表犹他大学医学院、亨茨曼癌症研究所、盐湖城退伍军人医疗中心的研究报告，利用大样本人口数据库分析了不同组织学亚型乳腺癌的家族高发性。
该研究利用犹他州人口数据库将家族谱系（家谱、家系、族谱、血统、血缘关系）记录与美国国家癌症研究所（NCI）监测流行病学最终结果（SEER）癌症登记数据库进行关联，根据组织学确定乳腺癌患者，并通过两两关联对组织学特定亚型共同遗传倾向证据进行检验，推算一级、二级、三级亲属之间的相对风险。
结果，从犹他州3百万人口数据库确定有家族史的原发乳腺浸润癌23629例，其中2883例（12.2%）为导管癌以外的特定组织学亚型：炎性癌178例、小叶癌1688例、黏液癌542例、管状癌134例、髓样癌341例。
远亲乳腺癌病例组与随机选择匹配对照组相比，家族谱系指数：
所有癌：2.37比2.38（P=0.676）
炎性癌：3.54比2.36（P=0.024）
小叶癌：2.36比2.40（P=0.619）
黏液癌：2.88比2.34（P=0.011）
管状癌：2.52比2.47（P=0.426）
髓样癌：2.12比2.33（P=0.723）
对于二级亲属，相对风险显著较高的特定组织学亚型乳腺癌：
炎性癌：高1.32倍（95%置信区间：1.02～1.68，P=0.03）
小叶癌：高1.36倍（95%置信区间：1.25～1.47，P<0.001）
黏液癌：高1.27倍（95%置信区间：1.12～1.44，P=0.00021）
因此，该研究结果表明，小叶癌、黏液癌、炎性癌的高发于乳腺癌家族，故有必要开展进一步研究以确定引起风险增加的潜在基因变异。分析特定组织学亚型乳腺癌高风险家族谱系可能成为有力的易感基因研究设计方法。
Cancer. 2019 May 23. [Epub ahead of print]
Breast cancer histologic subtypes show excess familial clustering.
Henry, NL, Cannon-Albright LA.
University of Utah School of Medicine, Salt Lake City, Utah; Huntsman Cancer Institute, Salt Lake City, Utah; Veterans Affairs Medical Center, Salt Lake City, Utah.
By using the Utah Population Database, the authors find evidence of histology-specific familial clustering for mucinous, lobular, and inflammatory breast carcinomas. Breast cancer cases with specific histologies appear to cluster more in pedigrees than expected, and the homogeneous pedigrees observed may be informative for identification of the predisposition genes responsible.
BACKGROUND: The inherited predisposition to developing specific histologic subtypes of invasive breast carcinoma has been incompletely investigated. By using a large, population-based database, the authors sought to investigate familial clustering of breast cancer by histologic subtype.
METHODS: By using the Utah Population Database, which links genealogy records to the National Cancer Institute's statewide Surveillance, Epidemiology, and End Results cancer registry, the authors identified patients with breast cancer by histology and tested for evidence of shared genetic predisposition to histologic specific subtypes by examining pairwise relatedness and estimating the relative risk (RR) among first-degree, second-degree, and third-degree relatives.
RESULTS: The authors identified 23,629 individuals in the Utah Population Database who had at least 3 generations of genealogy and at least 1 primary breast cancer, 2883 (12.2%) of which were specific histologic subtypes other than invasive ductal carcinoma (including inflammatory [n = 178], lobular [n = 1688], and mucinous [n = 542]). Statistically significant excess distant relatedness was identified for the mucinous subtype (P = .011) as well as for inflammatory breast cancers (P = .024). The RR for breast cancer of any histology in second-degree relatives was significantly increased for patients with inflammatory (RR, 1.32; 95% CI, 1.02-1.68; P = .03), lobular (RR, 1.36; 95% CI, 1.25-1.47; P < .001), and mucinous (RR, 1.27; 95% CI, 1.12-1.44; P = .00021) subtypes.
CONCLUSIONS: These findings provide evidence for significant familial clustering within histological subtypes for lobular, mucinous, and inflammatory breast carcinomas. Further research is required to identify the underlying genetic variants responsible for the increased risk. Studies of high-risk pedigrees segregating a specific histologic subtype could be a powerful design for predisposition gene identification.
KEYWORDS: breast cancer familiality inflammatory lobular mucinous Utah Population Database (UPDB)
DOI: 10.1002/cncr.32198
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