Relatives of Crohn's disease patients and breast cancer: An overlooked condition

AbstractRecent data suggest that patients suffering from Crohn’s disease (CD) may be at higher risk of developing extra-intestinal malignancies. This is attributed to inflammation and immunodepression due to medications. However, a genetic predisposition cannot ruled out. In the present study we investigated the prevalence of breast cancer in first-degree female relatives of CD patients compared with relatives of patients without evidence of gastrointestinal diseases. A total of 1302 female first-degree relatives of CD patients and 1294 relatives of controls were included. We found that CD was an independent risk factor for breast cancer development (OR = 2.76, 95% CI = 1.2–6.2; p = 0.017), and this is particularly evident in mothers (3.6% vs 1%, p = 0.009 − OR = 3.7, 95% CI 1.4–10). Among CD group, smoking habit of CD patients was associated with increased risk of cancer compared with relatives of non-smokers (7.7% vs 2.9%, p = 0.01 – OR = 2.8 95% CI 1.2–6.6). Intriguingly, stage at diagnosis was significantly higher in CD relatives (p = 0.04). Our findings suggest that first-degree female relatives of CD patients are at higher risk of developing breast cancer but receive diagnosis at more advanced stages, therefore advocating the need of more active screening protocol in this population

The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis

Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 × 10-12) and IRF4 (rs9405192, OR = 1.29, P = 1.4 × 10-14), fine-map the PLA2R1 locus (rs17831251, OR = 2.25, P = 4.7 × 10-103) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 × 10-49), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 × 10-93), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 × 10-23 and OR = 3.39, P = 5.2 × 10-82, respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20-37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk

Cytoreductive surgey and ovarian carcinoma

Purpose of investigation:the aim of this study is to demostrate if cytoreductive surgery in patients with ovarian carcinoma increases overall surviva

Fatigue in inflammatory bowel diseases: Relationship with age and disease activity

A higher rate of patients suffering from inflammatory bowel diseases (IBD) are reported to experience the symptom of fatigue compared with general population. Fatigue can impair quality of life of IBD patients by limiting their daily functioning. However, this problem is poorly understood and addressed. Our aim was to investigate the impact of fatigue in IBD patients compared with controls, and to seek for relation between age and disease activity. IBD patients aged between 16 and 75 years observed at our Unit from June 2011 through June 2012 were evaluated for fatigue. Patients were asked to fill the fatigue impact scale (FIS) questionnaire. A cohort of age- and sex-matched patients observed for other-than-IBD diseases were prospectively enrolled to act as controls. Patients diagnosed with malignancies were excluded from evaluation. Each group included 16 patients, of whom half aged over 65 years. Fatigue was more severe in IBD patients than in controls (p = 0.02), irrespective of age and disease activity. IBD patients with moderate to severe disease activity showed worse fatigue compared with controls at any age (p < 0.0001). Young IBD patients with low disease activity showed a trend toward worse FIS score when compared with old IBD counterparts (p = 0.06). IBD significantly impacted on fatigue in our series. Considering IBD patients in remission, younger patients may experience worse fatigue. Further studies are needed to explore the effects of fatigue on quality of life and the potential of appropriate intervention strategies

Copy Number Variant Analysis and Genome-wide Association Study Identify Loci with Large Effect for Vesicoureteral Reflux

BACKGROUND: Vesicoureteral reflux (VUR) is a common, familial genitourinary disorder, and a major cause of pediatric urinary tract infection (UTI) and kidney failure. The genetic basis of VUR is not well understood. METHODS: A diagnostic analysis sought rare, pathogenic copy number variant (CNV) disorders among 1737 patients with VUR. A GWAS was performed in 1395 patients and 5366 controls, of European ancestry. RESULTS: Altogether, 3% of VUR patients harbored an undiagnosed rare CNV disorder, such as the 1q21.1, 16p11.2, 22q11.21, and triple X syndromes ((OR, 3.12; 95% CI, 2.10 to 4.54; P=6.35×10(−8)) The GWAS identified three study-wide significant and five suggestive loci with large effects (ORs, 1.41–6.9), containing canonical developmental genes expressed in the developing urinary tract (WDPCP, OTX1, BMP5, VANGL1, and WNT5A). In particular, 3.3% of VUR patients were homozygous for an intronic variant in WDPCP (rs13013890; OR, 3.65; 95% CI, 2.39 to 5.56; P=1.86×10(–9)). This locus was associated with multiple genitourinary phenotypes in the UK Biobank and eMERGE studies. Analysis of Wnt5a mutant mice confirmed the role of Wnt5a signaling in bladder and ureteric morphogenesis. CONCLUSIONS: These data demonstrate the genetic heterogeneity of VUR. Altogether, 6% of patients with VUR harbored a rare CNV or a common variant genotype conferring an OR >3. Identification of these genetic risk factors has multiple implications for clinical care and for analysis of outcomes in VUR