How much of the predisposition to Hashimoto's thyroiditis can be explained based on previously reported associations?

Purpose Our insight in the genetics of Hashimoto’s thyroiditis (HT) has become clearer through information provided by genome-wide association studies and candidate gene studies, but remains still not fully understood. Our aim was to assess how many different genetic risk variants contribute to the development of HT. Methods 147 HT cases (10.2% men) and 147 controls (13.6% men) were qualified for the analysis. Intrinsic and environmental factors were controlled for. Polymorphisms (SNP) were chosen based on the literature and included markers of the genes PTPN22, CTLA4, TG, TPO among others, and of genomic regions pointed by GWAS studies. SNP were typed on a microarray. Variants in the HLA-DRB1 gene were identified by Sanger sequencing. Results Multivariate predisposition to HT was modeled. Based on the investigated group, a model of seven variables was obtained. The variability explained by this model was assessed at only 5.4821% (p = 2 × 10-6), which indicates that many dozens of factors are required simultaneously to explain HT predisposition. Conclusions We analyzed genetic regions commonly and most significantly associated with autoimmune thyroid disorders in the literature, on a carefully selected cohort. Our results indicated a lack of possibility to predict the risk of HT development, even with a multivariate model. We therefore conclude that strong associations of single genetic regions with HT should be interpreted with great caution. We believe that a change in the attitude towards genetic association analyses of HT predisposition is necessary. Studies including multiple factors simultaneously are needed to unravel the intricacies of genetic associations with HT

State of the art for gastric signet ring cell carcinoma: from classification, prognosis, and genomic characteristics to specified treatments

Julita Machlowska,1,* Małgorzata Pucułek,1,* Monika Sitarz,2 Paweł Terlecki,3 Ryszard Maciejewski,1 Robert Sitarz1,3 1Department of Human Anatomy, Medical University of Lublin, Lublin, Poland; 2Department of Conservative Dentistry and Endodontics, Medical University of Lublin, Lublin, Poland; 3Department of Surgery, St. John’s Cancer Center, Lublin, Poland *These authors contributed equally to this work Abstract: Gastric cancer (GC) is responsible for 9% of cancer deaths worldwide. Over 950,000 new cases are diagnosed each year, and about 90% of them are in advanced stage, requiring chemotherapy. In Europe there has been research based on pre- and postoperative chemotherapy treatment, using 5-fluorouracil, epirubicin, cisplatin, capecitabine, and docetaxel. Chemotherapy significantly impairs the quality of life of patients; however, the final effects are not always satisfactory. There is scientific evidence that gastric mucus tumors and signet ring cell carcinomas have a pattern of specific signatures, that distinguish them from other gastric cancer subtypes, and may be associated with a poor response to systematic treatment. Signet ring cell carcinoma is less chemosensitive than others, and the increase in the percentage of signet ring cells correlates with resistance to chemotherapy. Perioperative chemotherapy in advanced signet ring cell carcinomas is an independent factor of poor prognosis and survival, which is explained by the toxicity of neoadjuvant treatment. Therefore, curative surgical resection enhanced by standardized lymphadenectomy remains the recommended gold standard in GC therapy. According to presented studies, early detection and aggressive treatments for this subtype of GC is a reasonable approach. This review paper is mostly addressed to physicians who are interested in updating to the state of the art concerning different subtypes of gastric carcinoma. Keywords: gastric cancer, signet ring cells, CDH1, TP53, advanced stage, gastrectomy, adjuvant chemotherap