Single nucleotide polymorphisms rs911160 in AURKA and rs2289590 in AURKB mitotic checkpoint genes contribute to gastric cancer susceptibility.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in mitotic checkpoint genes could confer increased susceptibility to gastric cancer (GC). We investigated the association of Aurora kinase A (AURKA), Aurora kinase B (AURKB), Aurora kinase C (AURKC), Polo-like kinase 1 (PLK1) and Budding uninhibited by benzimidazol 3, yeast (BUB3) gene polymorphisms with GC risk. MATERIALS AND METHODS: Genotyping of 6 SNPs in AURKA (rs911160 and rs8173), AURKB (rs2289590), AURKC (rs11084490), PLK1 (rs42873), and BUB3 (rs7897156) was performed using TaqMan genotyping assays. RESULTS: Our study demonstrated that rs911160 (AURKA) heterozygous genotype was associated with an increased GC risk (OR = 1.50, 95% CI = 1.01-2.22, P = 0.043). Analysis of rs911160 (AURKA) showed significant association with an increased risk for intestinal type GC (OR = 1.80, 95%CI = 1.01-3.21, P = 0.040) and the risk was significantly higher in women than men (OR = 2.65, 95%CI = 1.02-6.87, P = 0.033). SNP rs2289590 in AURKB might contribute to susceptibility for the development of gastric cancer, particularly in women (OR = 2.08, 95% CI = 1.05-4.09, P = 0.032). CONCLUSION: Our findings suggested that AURKA (rs911160) and AURKB (rs2289590) polymorphisms could affect GC risk. Further validation studies in larger and multi-ethnical populations are needed to elucidate their functional impact on the development of GC. Environ. Mol. Mutagen. 58:701-711, 2017. © 2017 Wiley Periodicals, Inc.

Association of the AURKA and AURKC gene polymorphisms with an increased risk of gastric cancer.

Single nucleotide polymorphisms (SNPs) in mitotic checkpoint genes can contribute to susceptibility of human cancer, including gastric cancer (GC). We aimed to investigate the effects of Aurora kinase A (AURKA), Aurora kinase B (AURKB), and Aurora kinase C (AURKC) gene polymorphisms on GC risk in Slovenian population. We genotyped four SNPs in AURKA (rs2273535 and rs1047972), AURKB (rs2241909), and AURKC (rs758099) in a total of 128 GC patients and 372 healthy controls using TaqMan allelic discrimination assays to evaluate their effects on GC risk. Our results showed that genotype frequencies between cases and controls were significantly different for rs1047972 and rs758099 (P < 0.05). Our study demonstrated that AURKA rs1047972 TT and (CC + CT) genotypes were significantly associated with an increased risk of gastric cancer. Our results additionally revealed that AURKC rs758099 TT and (CC + CT) genotypes were also associated with increased GC risk. In stratified analysis, genotypes TT and (CC + CT) of AURKA rs1047972 SNP were associated with increased risk of both, intestinal and diffuse, types of GC. In addition, AURKC rs758099 TT and (CC + CT) genotypes were positively associated with increased intestinal type GC risk, but not with an increased diffuse type GC risk. Based on these results, we can conclude that AURKA rs1047972 and AURKC rs758099 polymorphisms could affect the risk of GC development. Further larger studies are needed to confirm these findings. © 2016 IUBMB Life, 68(8):634-644, 2016.

Laparoscopic rectal resection of deep infiltrating endometriosis.

PURPOSE: Deep infiltrating endometriosis with colorectal involvement is a complex disorder, often requiring segmental bowel resection. Complete removal of all visible lesions is considered the adequate treatment of infiltrating endometriosis in order to reduce recurrence. In this article, we describe our experience with laparoscopic management of deep infiltrating endometriosis with involvement of the rectum. METHODS: A retrospective analysis of data from patients with deep infiltrating endometriosis with rectal involvement who underwent a laparoscopic surgery in the years 2002-2009 at the Department of Obstetrics and Gynecology at our institution was done. RESULTS: Between 2002 and 2009, a laparoscopic partial rectal resection was performed in 52 patients, and laparoscopic disk resection was performed in 4 cases with deep infiltrating endometriosis. The mean age of patients was 34.4 years (range, 22-62 years). Preoperative symptoms included dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility. The laparoscopic procedure was converted to formal laparotomy in 3 patients (5.4%). The mean duration of surgery was 145 minutes. Postoperative complications included 3 cases of anastomotic leakage with rectovaginal fistula in two cases and intraabdominal bleeding in 1 case. The mean hospital stay was 7 days. Postoperatively, nine patients had a normal delivery, two of them after in vitro fertilization treatment. CONCLUSION: Laparoscopic rectal resection for deep infiltrating endometriosis is a relatively safe procedure, when performed by a surgeon and a gynecologist with sufficient experience in laparoscopic colorectal surgery.

A genomic approach to investigate expression profiles in Slovenian patients with gastric cancer.

Despite its decreasing frequency in developed countries, gastric cancer remains a significant health burden. The aim of the present study was to construct cDNA libraries and analyze differentially expressed genes related to this disease. Gene expression profiles were generated with suppressive subtraction hybridization (SSH). We constructed eight SSH libraries, four representing up-regulated genes and four representing down-regulated genes in tumor tissues. Our approach revealed that several genes are abnormally expressed in gastric cancer. We also identified global deregulation of several pathways involved in the maintenance of normal gastric homeostasis. The results of this study support the view that, as a result of complex pathogenesis, diversity of genomic aberrations and multiplicity of carcinogenic causes, gastric cancer cannot be reduced to a single molecule. Our results may contribute new insight into molecular aspects of the disease and may prove advantageous for future development of therapeutic targets and diagnostic molecular markers.

Genetic changes in Slovenian patients with gastric adenocarcinoma evaluated in terms of microsatellite DNA.

OBJECTIVES: Adenocarcinoma of the stomach is a relatively frequent malignant disease in Slovenia. We investigated the frequency of microsatellite instability (MSI) and loss of heterozygosity (LOH) in gastric carcinomas from the Slovenian population to determine their prognostic significance. METHODS: We evaluated MSI of mismatch repair associated loci and LOH on loci associated with following tumour suppressors: APC, nm23, Rb and p53. Results of the multiplex-PCR amplifications were correlated with clinicopathological factors for 73 patients. RESULTS: LOH was found in 52% of informative samples (20.5% LOH-H; 31.5% LOH-L). We found correlation of MSI with low-frequency LOH (LOH-L) in 11% of cases and with high-frequency LOH (LOH-H) tumours in 4% of cases. LOH-H and high-frequency MSI (MSI-H) were not associated. LOH was found in APC 36%, p53 33%, Rb 24% and nm23 33% of informative samples, whereas MSI was found in 30% of samples (12% MSI-H; 18% MSI-L). LOH-H status was associated with ulceration (P=0.029). LOH-N status was associated with diagnosis at higher TNM status (0.074) and infiltrative growth (P=0.006). Interestingly, in 6% of samples we found MSI on LOH loci as well. MSI-H was associated with higher age at diagnosis (r=0.24; P=0.04), antral location (r=0.252; P=0.04), intestinal type (P=0.044), expansive growth (P=0.001), tubular type (0.014), better differentiation (P=0.01), less nodal involvement (0.006) and better survival (P=0.022). The poorest prognosis was found in patients with both low-frequency MSI (MSI-L) and low-frequency LOH (LOH-L) tumours. CONCLUSION: The experimental design presented in the study may be of potential value for clinicians: at least five relevant markers for both MSI and LOH analysis may be needed to evaluate a gastric cancer (GC) patient's clinical status.

Significance of genetic abnormalities of p53 protein in Slovenian patients with gastric carcinoma.

AIM: To analyze genetic alterations of p53 gene in Slovenian gastric cancer patients and to compare these alterations with clinicopathological parameters in order to assess the value of p53 as a prognostic factor. METHODS: We analyzed the samples from 230 Slovenian patients with gastric cancer, collected between 1983 and 2001. p53 expression was evaluated immunohistochemically with DO-7 monoclonal antibody. In addition, loss of heterozigosity (LOH) and microsatellite instability (MSI) of p53 gene were evaluated, as well as its mutational status in the selected population of patients. RESULTS: p53 expression was associated with poorer survival and it was an independent predictor in multivariate analysis, along with TNM (T--size of tumor, N--nodal involvement, M--distant metastasis) stage status. Loss of heterozigosity and microsatellite instability status did not influence survival, however we found association of loss of heterozigosity with Lauren's (Mantel-Haenszel test, P=0.004) and Ming's (Mantel-Haenszel test, P<0.001) classification, whereas microsatellite instability was associated with gender (Mantel-Haenszel test, P=0.017), TNM stage (chi(2) test, P=0.006) of gastric cancer, and lymph node involvement (pN) (chi(2) test, P=0.004). Conclusions. The data on p53 abnormalities, when considered separately, could be of relative value for predicting the behavior of gastric tumors. However, our analyses showed that studying p53 overexpression, loss of heterozigosity, microsatellite instability, and mutational analysis could provide data that, particularly in combination with some clinicopathological features, might be of clinical value for predicting the tumor behavior and patient response to therapy.