Citations

Object Familial predisposition is a recognized nonmodifiable risk factor for the formation and rupture of intracranial aneurysms (IAs). However, data regarding the characteristics of familial IAs are limited. The authors sought to describe familial IAs more fully, and to compare their characteristics with a large cohort of nonfamilial IAs. Methods The Familial Intracranial Aneurysm (FIA) study is a multicenter international study with the goal of identifying genetic and other risk factors for formation and rupture of IAs in a highly enriched population. The authors compared the FIA study cohort with the International Study of Unruptured Intracranial Aneurysms (ISUIA) cohort with regard to patient demographic data, IA location, and IA multiplicity. To improve comparability, all patients in the ISUIA who had a family history of IAs or subarachnoid hemorrhage were excluded, as well as all patients in both cohorts who had a ruptured IA prior to study entry. Results Of 983 patients enrolled in the FIA study with definite or probable IAs, 511 met the inclusion criteria for this analysis. Of the 4059 patients in the ISUIA study, 983 had a previous IA rupture and 657 of the remainder had a positive family history, leaving 2419 individuals in the analysis. Multiplicity was more common in the FIA patients (35.6% vs 27.9%, p < 0.001). The FIA patients had a higher proportion of IAs located in the middle cerebral artery (28.6% vs 24.9%), whereas ISUIA patients had a higher proportion of posterior communicating artery IAs (13.7% vs 8.2%, p = 0.016). Conclusions Heritable structural vulnerability may account for differences in IA multiplicity and location. Important investigations into the underlying genetic mechanisms of IA formation are ongoing.

Abstract The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with the risk of ovarian cancer. Here, we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 OR, 1.10; 95% confidence interval (CI), 1.05–1.15; P = 3.49 × 10−5] and triple-negative (ER-, PR-, and HER2-negative) breast cancer (rs8170: OR, 1.22; 95% CI, 1.13–1.31; P = 2.22 × 10−7). However, rs8170 was no longer associated with ER-negative breast cancer risk when triple-negative cases were excluded (OR, 0.98; 95% CI, 0.89–1.07; P = 0.62). In addition, a combined analysis of triple-negative cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC; N = 3,566) identified a genome-wide significant association between rs8170 and triple-negative breast cancer risk (OR, 1.25; 95% CI, 1.18–1.33; P = 3.31 × 10−13]. Thus, 19p13.1 is the first triple-negative–specific breast cancer risk locus and the first locus specific to a histologic subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple-negative tumors and other subtypes likely arise through distinct etiologic pathways. Cancer Res; 72(7); 1795–803. ©2012 AACR.

ObjectiveTo determine whether patient factors (eg, indication for initial surgery, medical comorbidity, or age) are associated with adenoid regrowth and subsequent need for revision adenoidectomy and whether surgical factors (eg, surgical technique or level of surgeon’s training) are associated with adenoid regrowth and subsequent need for revision adenoidectomy.Study DesignHistorical cohort study.SettingTertiary care academic medical center.Subjects and MethodsChildren (≤18 years) who underwent adenoidectomy or adenotonsillectomy between 1980 and May 2009 were identified. Medical and surgical records were reviewed for sex, age at surgery, indication for surgery, training level of surgeon, surgical technique, and history of allergies, asthma, or gastroesophageal reflux disease.ResultsOf 8245 surgical cases (53.8% male), 163 were revision adenoidectomies. Age at initial adenoidectomy was a significant factor for revision adenoidectomy, with younger ages associated with higher increased risk. Indication for adenoidectomy was also a significant risk factor; adjusted for age, patients with ear rather than infectious indications were about 10 times more likely to require revision. A diagnosis of gastroesophageal reflux disease was a significant risk factor (hazard ratio, 2.23; P =. 002).ConclusionSeveral risk factors are associated with revision adenoidectomy: young age at initial procedure, indication for adenoidectomy, and diagnosis of gastroesophageal reflux disease. Surgical technique, level of experience of the initial surgeon, and diagnosis of asthma or allergies were not significant risk factors for revision adenoidectomy.