Prevalence and Risk Factors of Germline Pathogenic Variants in Pancreatic Ductal Adenocarcinoma / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The genetic attribution for pancreatic ductal adenocarcinoma (PDAC) has been reported as 5%-10%. However, the incidence of germline pathogenic variants (PVs) in Korean PDAC patients has not been thoroughly investigated. Therefore, we studied to identify the risk factors and prevalence of PV for future treatment strategies in PDAC. @*Materials and Methods@#Total of 300 (155 male) patients with a median age of 65 years (range, 33 to 90 years) were enrolled in National Cancer Center in Korea. Cancer predisposition genes, clinicopathologic characteristics, and family history of cancer were analyzed. @*Results@#PVs were detected in 20 patients (6.7%, median age 65) in ATM (n=7, 31.8%), BRCA1 (n=3, 13.6%), BRCA2 (n=3), and RAD51D (n=3). Each one patient showed TP53, PALB2, PMS2, RAD50, MSH3, and SPINK1 PV. Among them, two likely PVs were in ATM and RAD51D, respectively. Family history of various types of cancer including pancreatic cancer (n=4) were found in 12 patients. Three patients with ATM PVs and a patient with three germline PVs (BRCA2, MSH3, and RAD51D) had first-degree relatives with pancreatic cancer. Familial pancreatic cancer history and PVs detection had a significant association (4/20, 20% vs. 16/264, 5.7%; p=0.035). @*Conclusion@#Our study demonstrated that germline PVs in ATM, BRCA1, BRCA2, and RAD51D are most frequent in Korean PDAC patients and it is comparable to those of different ethnic groups. Although this study did not show guidelines for germline predisposition gene testing in patients with PDAC in Korea, it would be emphasized the need for germline testing for all PDAC patients.

Phenotypic Analysis of Korean Patients with Abnormal Chromosomal Microarray in Patients with Unexplained Developmental Delay/Intellectual Disability

PURPOSE: The present study aimed to investigate chromosomal microarray (CMA) and clinical data in patients with unexplained developmental delay/intellectual disability (DD/ID) accompanying dysmorphism, congenital anomalies, or epilepsy. We also aimed to evaluate phenotypic clues in patients with pathogenic copy number variants (CNVs). MATERIALS AND METHODS: We collected clinical and CMA data from patients at Konyang University Hospital between September 2013 and October 2014. We included patients who had taken the CMA test to evaluate the etiology of unexplained DD/ID. RESULTS: All of the 50 patients identified had DD/ID. Thirty-nine patients had dysmorphism, 19 patients suffered from epilepsy, and 12 patients had congenital anomalies. Twenty-nine of the 50 patients (58%) showed abnormal results. Eighteen (36%) were considered to have pathogenic CNVs. Dysmorphism (p=0.028) was significantly higher in patients with pathogenic CNVs than in those with normal CMA. Two or more clinical features were presented by 61.9% (13/21) of the patients with normal CMA and by 83.3% (15/18) of the patients with pathogenic CMA. CONCLUSION: Dysmorphism can be a phenotypic clue to pathogenic CNVs. Furthermore, pathogenic CNV might be more frequently found if patients have two or more clinical features in addition to DD/ID.

Response to Nonallergenic Irritants in Children With Allergic and Nonallergic Rhinitis

PURPOSE: Nonallergenic irritants can aggravate the symptoms of rhinitis. We investigated the clinical responses of children with allergic rhinitis (AR) and nonallergic rhinitis (NAR) to nonallergenic irritants, and identified factors associated with these responses. METHODS: Children with chronic rhinitis (n=208) were classified as having AR or NAR based on the presence of aeroallergen-specific IgE. Healthy controls (n=24) were recruited for comparison. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines were used to classify patients, and their irritant score (0-21 points) and current symptom score (5-35 points) were measured. Subjects with irritant scores ≥3 and <3 were classified as having irritant and nonirritant rhinitis, respectively. RESULTS: The mean age of enrolled subjects was 6.8 years (range: 1.8-16.0 years). The AR and NAR groups had similar irritant scores (P=0.394) and proportions of subjects with irritant scores ≥3 (P=0.105). Irritant score correlated positively with symptom score (P=0.005), and the proportion of subjects with irritant scores ≥3 was greater in children with moderate-severe rhinitis than in those with mild rhinitis (P=0.046). Multiple logistic regression analysis indicated that the presence of atopic eczema increased the risk for sensitivity to a nonallergenic irritant (aOR=2.928, 95% CI 1.567-5.473, P=0.001). CONCLUSIONS: Response to a nonallergenic irritant was useful for gauging the severity of rhinitis, but not for differentiating AR from NAR. AR and NAR patients with atopic eczema may increase nasal sensitivity to nonallergenic irritants.

Relationship between exhaled nitric oxide and small-airway dysfunction in children with asthma using spirometry and the impulse oscillometry system

PURPOSE: Fractional exhaled nitric oxide (FeNO) is a maker of airway inflammation, and impedance of low frequency in the impulse oscillometry system (IOS) reflects small-airway obstruction. We investigated the association of the FeNO level with IOS parameters and spirometry results in asthma patients. METHODS: Fifty-eight children with asthma (60.3%, male), mean age 8.3 years (range, 4.5-16.0 years), were enrolled in the study. Reactance and resistance at 5 Hz with IOS, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and forced expiratory flow 25%-75% of the vital capacity (FEF25%-75%) with spirometry and FeNO were measured in all patients. The Z-score of spirometry and IOS parameters and the mean level of FeNO were used for correlation and regression analysis. RESULTS: FeNO was not significantly associated with height, age, or other demographic parameters. There was a statistically significant correlation between spirometry results and IOS measurements. The FeNO level was not significantly correlated with IOS variables. After adjusting for height, sex, atopic status, and the use of inhaled corticosteroid, the FeNO level showed significant correlations with Z-score of FEV1/FVC (P=0.037, adjusted R 2=0.234). CONCLUSION: FeNO was significantly correlated with Z-scores of FEV1/FVC, but not with IOS variables. Therefore, FeNO may be used to detect whole airway obstruction, but not small-airway obstruction.