Genetic determinants of taxane-induced peripheral neuropathy.

The efficacy of taxane­containing regimens has been demonstrated for various cancers, particularly ovarian, endometrial, breast, lung, and prostate cancers. However, extensive taxane-induced toxicities limit their use. Prediction and management of many toxic complications in cancer patients have evolved significantly over the last decade. Peripheral neuropathy is the most typical non-hematological taxane-related complication, and it has a multifactorial pathogenesis. It is often dose-dependent and progressive during therapy and sometimes even after treatment. Unfortunately, the prediction of these common adverse events remains unclear. In the past few years, several polymorphisms of candidate genes with a possible role in the development of this consequence were studied. This minireview aims to highlight the critical yet underappreciated roles of genetic predictors that may increase susceptibility to taxane-induced peripheral neuropathy in cancer patients (Ref. 40). Keywords: taxanes, paclitaxel, docetaxel, peripheral neuropathy, risk factors, genetic polymorphisms.

New trends in criteria indicative of neoadjuvant oncological therapy of lower and middle rectal cancers.

The indication for primary surgical resection or neoadjuvant therapy in lower and middle rectal cancers is often disputable. The aim of the study was to evaluate the occurrence of local recurrence of rectal cancer as for a period of at least 4 years after radical resection. The second aim was to evaluate and compare the results of preoperative magnetic resonance (MR) staging with definitive histology.From September 2013 to December 2017, we, at the 3rd Surgical Department Comenius University, Bratislava, prospectively evaluated patients with lower and middle rectal cancers with the distal tumor border being in a 12-cm distance from the anal verge. All patients underwent MR examination at the same MRI department and were operated on at the 3rd Surgical Department, Comenius University, Bratislava. Inclusion criteria included parameters based on MRI examination, i.e., T-staging of T1-T3b, negative extramural vascular infiltration (EMVI), negative circumferential margin (CRM), no mesorectal fascia infiltration with a distance of more than 2 mm. We did not take lymph node staging into account in the indication for primary surgical resection. We performed a radical primary resection procedure (R0 resection) in all patients. The group consisted of 87 patients, of whom 49 were men and 38 were women. The mean age of the patients was 66 years (min. 36 - max. 86 years). Our study also shows significant differences in preoperative T and N staging as compared to definitive histology. The incidence of local recurrence during a period of at least 4 years after surgery was 6.76 %. Study also shows that the indication for preoperative radiotherapy for lower and middle rectal cancers based on N status is inaccurate and leads to unnecessary indications for preoperative radiotherapy which may decrease the patients´ quality of life and increase the post­operative complications. We have also shown that leaving out the N-based radiotherapy from indications does not lead to an increase in the number of local recurrences in lower and middle rectal cancers (Tab. 1, Fig. 5, Ref. 22). Text in PDF www.elis.sk Keywords: rectal cancer, neoadjuvant therapy, local recurrence.

Risk genetic polymorphism and haplotype associated with papillary thyroid cancer and their relation to associated diseases in Slovak population.

BACKGROUND: Risk for developing papillary thyroid carcinoma (PTC), the most common endocrine malignancy, is thought to be mediated by lifestyle, environmental exposures and genetic factors. Recent progress in the genome-wide association studies of thyroid cancer leads to the identification of several genetic variants conferring risk to this malignancy across different ethnicities. METHODS AND RESULTS: We set out to elucidate the impact of selected single nucleotide polymorphisms (SNPs) on papillary thyroid carcinoma risk and to evaluate the interactions of these genetic variants with associated diseases for the first time in the Slovak population. Six SNPs (rs966423, rs2439302, rs965513, rs116909374, rs1537424 and rs944289) were genotyped in 86 patients with PTC and 99 healthy control subjects. The association analysis and multivariable modelling of PTC risk by the genetic factors, supplemented with a rigorous statistical validation, were performed. One of the six SNPs rs966423 (DIRC3, OR=1.51, p=0.03) was significantly associated with PTC. Next two SNPs rs965513 (PTCSC2, OR=1.34) and rs116909374 (MBIP, OR=0.44) showed a suggestive association. Haplotype TTC (SNPs located on chromosome 14q13) showed a suggestive association with PTC (p=0.07, OR=1.55). In the PTC group, significant associations were observed between rs966423 (DIRC3) and ischemic heart diseases (p=0.009), rs965513 (PTCSC2) and diabetes mellitus (p=0.04) and haplotype 14q13 and musculoskeletal diseases. Next three associations rs966423 (DIRC3) and arterial hypertension; rs116909374 (MBIP) and other benign diseases; rs1537424 (MBIP) and disorder lipid metabolism, rs965513 (PTCSC2) and anti-Tg (thyroglobulin antibody) showed suggestive associations. CONCLUSION: These results indicate that germline variants not only predispose to PTC, but may also be related to other risk factors, including associated diseases. However, these associations were only moderate, and further multi-ethnic studies are required to evaluate the usefulness of these germline variants in the clinical stratification of PTC patients (Tab. 8, Ref. 37).