Prevalence of BRCA1 and BRCA2 pathogenic sequence variants in ovarian cancer patients in the Gulf region: the PREDICT study.

BACKGROUND: Patients with pathogenic sequence variants (PSVs) in BRCA1/BRCA2 are at high risk of developing ovarian cancer (OC). However, genetic testing for BRCA1/BRCA2 PSVs is still not a routine practice in the Middle East. With the lack of epidemiological studies in the region, we aim to describe the prevalence of BRCA1/BRCA2 PSVs in patients with OC across different countries in the Gulf region. METHODS: The PREDICT study was an observational, prospective, epidemiological study, which consecutively recruited women with ovarian, primary peritoneal, and fallopian tube cancers from the following Gulf countries over the period from July 2017 to July 2019; United Arab Emirates (UAE), Kuwait, and Oman. The study was approved by the local ethics committee of participating centers. The BRCA1/BRCA2 PSVs were assessed by tissue genetic testing using next-generation sequencing (NGS). RESULTS: A total of 105 women were included with a median age at diagnosis of 52 years (IQR 44.5 - 61.0). Nearly 11.4% of patients reported a family history of ovarian or breast cancer, while 4.7% of patients reported a family history of other cancers. Most of the patients (70.3%) had advanced disease (FIGO stage III/IV) at presentation. Eighty-eight patients (84%) were successfully tested for somatic BRCA1/BRCA2 PSVs. Fifteen patients (17%) were found to have PSVs in either BRCA1, BRCA2, or both genes; of them, 10 patients (11.2%) had BRCA1 somatic PSVs alone, eight patients (9.1%) had BRCA2 somatic PSVs, while three patients (2.9%) had both PSVs. Five patients with BRCA1/BRCA2 somatic PSVs had germline PSVs tests, and three of them tested positive. Concerning treatment, 87.6% of patients received perioperative chemotherapy and 6.6% as first-line palliative chemotherapy. Eighty-seven (82.9%) patients underwent debulking surgery, with no residual disease in 42.5% of patients. CONCLUSION: Our study showed that the prevalence of BRCA1/BRCA2 somatic PSVs in patients with OC is higher than the reported global figures (2-8%). However, more studies are warranted to further elucidate the prevalence of BRCA1/BRCA2 somatic and germline PSVs, as well as other relevant genetic alterations, to better understand their impact on OC patient outcomes in Gulf countries. TRIAL REGISTRATION: NCT03082976 .

Clinicopathological and immunological characteristics and outcome of concomitant coeliac disease and non-alcoholic fatty liver disease in adults: a large prospective longitudinal study.

OBJECTIVE: Concomitant non-alcoholic fatty liver disease (NAFLD) and coeliac disease (CD) have not been adequately studied. This study investigated the frequency of CD among NAFLD patients and the clinicopathological and immunological patterns and outcome of concomitant NAFLD and CD. DESIGN: This prospective longitudinal study screened patients with NAFLD for CD (tissue transglutaminase antibodies (TTGA); anti-TTGA and antiendomysial antibodies (EMA)). Patients with concomitant NAFLD and CD and patients with either NAFLD or CD were enrolled and followed. Duodenal biopsy, transient elastography, tumour necrosis factor (TNF)-alpha, transforming growth factor-beta, interleukins (ILs) 1, 6, 10, 15 and 17, folic acid and vitamins B12 and D were performed at baseline and 1 year after gluten-free diet (GFD). RESULTS: CD was confirmed in 7.2% of patients with NAFLD. Refractory anaemia and nutritional deficiencies were frequent in patients with concomitant NAFLD and CD who had advanced intestinal and hepatic lesions, higher levels of TNF-α, IL-15 and IL-17 compared with patients with CD and NAFLD. Patients concomittant CD and NAFLD showed clinical response to GFD, but intestinal histological improvement was suboptimal. Combining EMA-IgA or anti-TTGA with either IL-15 or IL-17 enhances the prognostic performance of both tests in predicting histological response to GFD. CONCLUSION: Concomitant NAFLD and CD is not uncommon. Recurrent abdominal symptoms, refractory anaemia, nutritional deficiencies in patients with NAFLD warrant screening for CD. The study has important clinical implications since failure in diagnosing CD in patients with NAFLD patients results in marked intestinal and hepatic damage and suboptimal response to GFD that can be alleviated by early diagnosis and initiation of GFD.