Recurrent BRCA1 Mutation,but no BRCA2 Mutation,in Vietnamese Patients with Ovarian Carcinoma Detected with Next Generation Sequencing

Background: Identification of germline and somatic BRCA1/2 mutations in ovarian cancer is important for genetic counseling and treatment decision making with poly ADP ribose polymerase inhibitors. Unfortunately, data on the frequency of BRCA1/2 mutations in Vietnamese patients are scare. Methods: We aim to explore the occurrence of BRCA1/2 mutations in 101 Vietnamese patients with ovarian cancer including serous (n = 58), endometrioid (n = 14), mucinous (n = 24), and clear cell (n = 5) carcinomas. BRCA1/2 mutations were detected from formalin-fixed parafin-embedded tumor samples using the OncomineTM BRCA Research Assay on Personal Genome Machine Platform with Ion Reporter Software for sequencing data analysis. The presence of pathogenic mutations was confirmed by Sanger sequencing. Results: We found no BRCA2 mutation in the entire cohort. Four types of pathogenic mutations in BRCA1 (Ser454Ter, Gln541Ter, Arg1751Ter, and Gln1779AsnfsTer14) were detected in 8 unrelated patients (7.9%) belonging to serous and endometrioid carcinoma groups. Except for the c.1360_1361delAG (Ser454Ter) mutation in BRCA1 exon 11 that was somatic, the other mutations in exons 11, 20, and 22 were germline.  Interestingly, the recurrent Arg1751Ter mutation in BRCA1 exon 20 appeared in 4 patients, suggesting that this is a founder mutation in Vietnamese patients. Conclusion: Mutational analysis of tumor tissue using next generation sequencing allowed the detection of both germline and somatic BRCA1/2 mutations.     

Association between Hepatitis B Surface Antigen Levels and the Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Infection: Systematic Review and Meta-Analysis

Background: The role of hepatitis B surface antigen (HBsAg) levels in predicting the risk of developinghepatocellular carcinoma (HCC) has remained unclear. The aim of this study was to obtain the most up-to-date estimatedmeasure of the association between HBsAg levels and the development of HCC in patients. Methods: We performed asystematic review by searching for relevant studies on PubMed, Scopus, ProQuest and the Cochrane Central Registerof Controlled Trials from January 2002 to November 2017. We presented the effects of HBsAg levels at each cut-offvalue as the odds ratios (ORs) at 95% confidence interval (CI). We also investigated HCC and its potential risk factorsincluding HBeAg, and HBV DNA. We registered our protocol with the International Prospective Register of SystematicReviews (PROSPERO) with the registration number CRD42018081138. Results: We selected 10 studies representing12 541 cases. At the 100 IU/ml cut-off, the OR for HCC at the high HBsAg level versus the low level was 4.99 (95%CI, 3.01–8.29) with high inconsistency (I2=79%). At the 1,000 IU/ml threshold, the pooled OR for HCC at the highHBsAg versus the low level was 2.46 (95% CI, 2.15–2.83) with low variance. We also found correlations between therisk of HCC and male gender (OR=2.12), hepatitis B e-antigen positivity (OR=2.99), or hepatitis B (HBV) viral load≥ 2,000 IU/ml (OR=4.37). Conclusion: Our study revealed that HBsAg levels ≥ 100 IU/ml, and notably >1,000 IU/ml, are associated with an increased risk of HCC development.     

Pre-implantation Genetic Diagnosis: The Road Forward in Canada

The use of pre-implantation genetic diagnosis (PGD) is increasing as the list of indications it can test for constantly expands. This raises new challenges for clinicians and prospective parents regarding possible uses and calls for guidance. Policy approaches towards PGD vary greatly worldwide. The 2004 Canadian Assisted Human Reproduction Act does not provide guidance, except for prohibiting non-medical sex selection. Criminal legislation is an unsuitable policy instrument to regulate human genetics and reproductive medicine. We call for professional societies to issue guidelines regarding the uses of PGD that would establish the standard of care and legal norms. Such guidelines should be based on a patient-centered approach and respect individual autonomy in reproductive decision-making. Canadian approaches to PGD should also consider issues related to equity of access. Moreover, since PGD often raises concerns about eugenic uses, guidelines should also consider its societal impact and its implementation should be accompanied by policies that maintain or increase social support for people with disabilities. Finally, public engagement could provide an evidence-base regarding Canadian societal values and concerns that should guide regulatory reform, for example, the regulation of non-medical sex selection through PGD.