期刊
CANCER
卷 125, 期 18, 页码 3131-3138出版社
WILEY
DOI: 10.1002/cncr.32198
关键词
breast cancer; familiality; inflammatory; lobular; mucinous; Utah Population Database (UPDB)
类别
资金
- NCI NIH HHS [HHSN261201800016I, HHSN261201800016C, P30 CA042014] Funding Source: Medline
- Utah Cancer Registry Funding Source: Medline
- Huntsman Cancer Foundation Funding Source: Medline
- CDC HHS [NU58DP0063200-01] Funding Source: Medline
- Huntsman Cancer Institute [P30 CA42014] Funding Source: Medline
- University of Utah Funding Source: Medline
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.
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