Allen-Brady Kristina, Camp Nicola J, Ward John H, Cannon-Albright Lisa A
Genetic Epidemiology, Department of Medical Informatics, University of Utah School of Medicine, Salt Lake City, 84108, USA.
Int J Cancer. 2005 Nov 20;117(4):655-61. doi: 10.1002/ijc.21236.
Family history of breast cancer (BC) is a strong predictor for developing female BC. Whether this excess familiality differs within morphological BC subgroups remains unclear. We assessed the risk of lobular breast cancer (LOB) and any BC among relatives of probands with LOB. We used the Utah Population Database (UPDB) to estimate familial relative risks (FRR) as well as average relatedness, using the genealogical index of familiality (GIF) statistic. The UPDB, a population-based resource, links genealogical data from over 2 million individuals to the Utah Cancer Registry. Consistent with other studies, analysis of all BC cases showed significantly increased risk of BC to relatives (first-degree relative [FDR]: FRR = 1.83, 95% confidence interval [CI] = 1.75-1.90). Morphology-specific risks showed that relatives of LOB probands had an increased risk of LOB (FDR: FRR = 4.51, 95% CI = 2.79-6.89) and an increased risk of any BC (FDR: FRR = 2.47, 95% CI = 2.12-2.85); both measures were significantly greater than the all BC FRR estimates, and surpassed even generalized early-onset BC risk. GIF analyses corroborated the FRR results and indicated that the excess relatedness of LOB cases extended to third-degree relatives. Our findings suggest that LOB has a heritable component and may represent a genetically homogeneous form of BC. Pedigrees with excess LOB may be useful in isolating additional BC predisposition genes. Relatives of women with LOB are at higher risk for BC than relatives of other BC subtypes; a more rigorous BC screening regime may be warranted for these individuals.
乳腺癌（BC）家族史是女性患BC的一个有力预测指标。这种家族性增加在BC形态学亚组中是否存在差异尚不清楚。我们评估了小叶性乳腺癌（LOB）患者亲属患LOB及任何类型BC的风险。我们使用犹他州人口数据库（UPDB），通过家族性系谱指数（GIF）统计量来估计家族相对风险（FRR）以及平均亲缘关系。UPDB是一个基于人群的资源库，将超过200万人的系谱数据与犹他州癌症登记处相链接。与其他研究一致，对所有BC病例的分析显示，亲属患BC的风险显著增加（一级亲属[FDR]：FRR = 1.83，95%置信区间[CI] = 1.75 - 1.90）。形态学特异性风险显示，LOB先证者的亲属患LOB的风险增加（FDR：FRR = 4.51，95% CI = 2.79 - 6.89），患任何类型BC的风险也增加（FDR：FRR = 2.47，95% CI = 2.12 - 2.85）；这两项指标均显著高于所有BC的FRR估计值，甚至超过了一般早发性BC的风险。GIF分析证实了FRR结果，并表明LOB病例的额外亲缘关系延伸至三级亲属。我们的研究结果表明，LOB具有遗传成分，可能代表一种基因同质的BC形式。LOB过多的家系可能有助于分离出更多的BC易感基因。与其他BC亚型患者的亲属相比，LOB女性患者的亲属患BC的风险更高；可能需要对这些个体采取更严格的BC筛查方案。
