| 1. |
- Alehagen, Urban, 1951-, et al.
(författare)
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Increased mortality in the A/A genotype of the SNP rs28372698 of interleukin 32
- 2021
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Ingår i: Experimental and Therapeutic Medicine. - : SPANDIDOS PUBL LTD. - 1792-0981 .- 1792-1015. ; 21:2
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Tidskriftsartikel (refereegranskat)abstract
- One of the major causes of mortality in the western hemisphere is cardiovascular disease. Therefore, a variety of markers to identify those at risk are required. Interleukin-32 (IL-32) is a cytokine that is associated with inflammation. The aim of the current study was to investigate variations in single nucleotide polymorphisms (SNPs) of IL-32 and plasma expression, and their associations with mortality. A population of 486 elderly community-living persons were evaluated. The participants were followed for 7.1 years and underwent a clinical examination and blood sampling. SNP analyses of IL-32 rs28372698 using allelic discrimination and plasma measurement of IL-32, using ELISA, were performed. During the follow-up period, 140 (28.8%) all-cause and 87 (17.9%) cardiovascular deaths were registered. No significant difference between mortality and plasma concentration of IL-32 was observed. The A/A genotype group exhibited significantly higher all-cause mortality (P=0.036), and an almost two-fold increased risk in a multivariate Cox regression model for all-cause and cardiovascular mortality. A highly significant difference in all-cause and cardiovascular mortality between the A/A and the T/T groups was demonstrated (P=0.015 resp. P=0.014). In the present study, the cytokine IL-32 was demonstrated to have prognostic information, with an increased risk of all-cause and cardiovascular mortality for those with the A/A genotype rs28372698 of IL-32. The A/A genotype could therefore be regarded as a possible biomarker for mortality risk that may be used to offer optimized cardiovascular patient handling in the future. However, the present study sample was small, and the results should be regarded as hypothesis-generating.
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| 2. |
- Dimberg, Jan, et al.
(författare)
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Effects of diabetes type 2 and metformin treatment in Swedish patients with colorectal cancer
- 2022
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Ingår i: World Journal of Gastroenterology. - : Baishideng Publishing Group Inc.. - 1007-9327 .- 2219-2840. ; 28:19, s. 2148-2151
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The association between type 2 diabetes mellitus (DM) and colorectal cancer (CRC) has been thoroughly investigated and reports have demonstrated that the risk of CRC is increased in DM patients. The association between DM and the survival of patients with CRC is controversial. Evidence suggests that metformin with its anti-inflammatory effects is a protective factor against the development of CRC among DM patients and that metformin therapy is associated with a better prognosis in patients with DM. In our cohort, we did not find any associations between the presence of DM or metformin and cancer specific survival or any relation to plasma levels of a panel of 40 inflammatory factors and irisin. On the other hand, we identified that the insulin-like growth factor binding protein 7 single nucleotide polymorphism rs2041437 was associated with DM in CRC patients. The dominance of the T bearing genotypes in patients with DM was statistically significant (P = 0.038), with an odds ratio of 1.66 (95% confidence interval: 1.03-2.69).
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| 3. |
- Dimberg, Jan, et al.
(författare)
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Emerging role and clinical implication of mRNA scavenger decapping enzyme in colorectal cancer
- 2023
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Ingår i: Pathology, Research and Practice. - : Elsevier. - 0344-0338 .- 1618-0631. ; 253
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Turnover of RNA is a regulated process that in part controls gene expression. This process is partly controlled by the scavenger decapping enzyme (DcpS). This study aimed to investigate the expression of DcpS in colorectal cancer (CRC) tissue, to evaluate its prognostic significance in patients with CRC and to investigate potentially targeted genes by DcpS.METHODS: Immunohistochemical analysis was used to determine localization of DcpS in normal and CRC tissue, western blot analysis for quantification of protein expression and qPCR for mRNA expression in normal and CRC tissue and expression in cell lines after silencing using siRNA. Gene array analysis was used to study regulation of genes after silencing of DcpS. Proliferation was studied using BRDU.RESULTS: DcpS expression was localized to the epithelial cells of both control and cancer tissue. Tumor and paired control tissue samples from 100 patients who underwent surgical resection for primary colorectal adenocarcinomas were utilized. mRNA and protein of DcpS was significantly up-regulated in the patients with CRC and the mRNA level was higher in rectal cancer tissue compared to colon cancer tissue (p < 0.05). Lowest tertile levels of DcpS mRNA in cancer tissue was associated with a decreased cancer-specific survival rate with a hazard ratio (HR) of 4.7 (95% CI=1.02-12.3), independent of disease stage. The low level of DcpS mRNA was a predictor of poorer survival in patients with rectal and disseminated cancer and in patients receiving adjuvant treatment (p < 0.05). After silencing DcpS in Caco-2 cancer cells, altered expression of several genes associated with RNA, cell cycle regulation, alternative splicing and microRNA was observed and resulted in 23% increase in proliferation.CONCLUSIONS: These results indicate that DcpS has potential as a prognostic factor for CRC but further studies in a broader cohort are warranted to evaluate the significance of the findings in the clinic.
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| 4. |
- Dimberg, Jan, et al.
(författare)
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Genetic Variants of the IL2 Gene Related to Risk and Survival in Patients With Colorectal Cancer
- 2019
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Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 39:9, s. 4933-4940
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Tidskriftsartikel (refereegranskat)abstract
- Background: Interleukin 2 (IL2) is a significant factor activating T-cell-mediated immune response by stimulation of natural killer cells, T-cells and in development of regulatory T (Treg) cells. Recent studies have that IL2 participates in cancer development by modifying the local immune response. Based on the suggested role of the single nucleotide polymorphisms (SNPs) rs2069762, rs6822844 and rs11938795 of IL2 in the pathogenesis of certain diseases, the relationship of these SNPs with clinicopathological variables and their possible implication for prognosis and disease outcome were evaluated in a cohort of Swedish patients with colorectal cancer (CRC). Materials and Methods: TaqMan SNP genotype assays based on polymerase chain reaction were used for analysis of the IL2 SNPs in 467 patients with CRC and 467 healthy controls. Expression analysis of IL2 in plasma and CRC tissue was also performed. Results: The allelic variants T in rs11938795 and G in rs6822844 were significantly associated with a higher risk of CRC. Kaplan-Meier analysis showed that cancer-specific survival was worse for individuals with C allele for rs2069762 with stage II CRC and with T allele for rs6822844 with stage III CRC. Conclusion: SNPs rs2069762, rs6822844 and rs11938795 of the IL2 gene may be helpful as prognostic biomarkers in the follow-up and management of the patients.
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| 5. |
- Nguyen, Song Van, et al.
(författare)
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Clinicopathological and prognostic value of CD44 gene polymorphism (rs187115) in Swedish patients with colorectal cancer
- 2023
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Ingår i: Nucleosides, Nucleotides & Nucleic Acids. - : Taylor & Francis. - 1525-7770 .- 1532-2335. ; 42:10, s. 807-817
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Tidskriftsartikel (refereegranskat)abstract
- Cluster of differentiation (CD) 44 plays a crucial role in apoptosis, cell-cell interactions, angiogenesis, metastasis and proliferation. The aim of the present study was to examine the influence of CD44 gene polymorphism rs187115 on colorectal cancer (CRC) susceptibility and the association with various clinical features including long-term survival in Swedish patients with CRC. Genotypes were screened, using TaqMan single nucleotide polymorphism (SNP) assays based on polymerase chain reaction, in 612 CRC patients and 575 healthy controls.The carriers of G allele, genotypes (AG + GG), were found to be associated with an increased risk of CRC with an odds ratio (OR) of 1.35 (95% confidence interval (CI) = 1.01-1.81; p = 0.039) and found to be more common in patients with mucinous cancer compared with non-mucinous cancer, OR = 1.69 (95% CI = 1.02-2.80; p = 0.011). By using Kaplan-Meier analysis, the patients with genotype GG showed shorter cancer-specific and recurrence free survival with a hazard ratio (HR) of 1.25 (95% CI = 1.02-1.54; p = 0.036) and 1.52 (95% CI = 1.12-2.06; p = 0.007), respectively, in comparison with the carriers of A allele (AG + AA). The present findings demonstrated that the variant G allele of CD44 gene polymorphism rs187115 was related to risk for CRC and associated to mucinous cancer and predict worse prognosis in Swedish patients with CRC.
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| 6. |
- Oliva, Delmy, et al.
(författare)
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Single nucleotide polymorphism directed antiemetic treatment in women with breast cancer treated with neo- or adjuvant chemotherapy : a randomised multicentre phase II study. (EudraCT: 2015–000658-39)
- 2023
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 43:6, s. 2671-2681
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Tidskriftsartikel (refereegranskat)abstract
- Background/aim: The role of single nucleotide polymorphisms (SNPs) in the frequency and intensity of chemotherapy-induced nausea and vomiting (CINV) in women with breast cancer (BC) is unclear. The primary purpose of this study was to compare/evaluate the effect of SNP-guided antiemetic treatment versus standard CINV treatment.Patients and methods: A randomised, factorial, phase II multicentre study design was used. Women planned for neoadjuvant or adjuvant chemotherapy with epirubicin, cyclophosphamide and fluorouracil (FEC /EC, with or without fluorouracil) for BC were randomised to SNP-guided antiemetic treatment (based on the results of SNP analyses) versus standard CINV treatment. Blood samples were taken before the treatment was initiated. Patient-reported data on CINV (during 10 days from onset of cancer treatment) and health-related quality of life (HRQoL), were collected before and after the first cancer treatment.Results: A total of 188 women were included. Overall, nausea was reported by 86% (n=129) of the patients during the ten-day period from the start of cancer treatment. The SNP genotype studied varied. In FAS-CD95, the genotypes AG and GG were overrepresented; in RB1-LPAR6, GG was overrepresented, and in CCL2, both AA and GG were overrepresented. We found no statistically significant difference in CINV between SNP-guided antiemetic treatment versus standard CINV treatment.Conclusion: SNP-guided antiemetic treatment could be as effective as standard treatment. SNP-guided antiemetic treatment of CINV is possibly useful in detecting patients with a higher or lower risk for CINV and thus may help in avoiding over-treatment with toxic components. CINV negatively affects the HRQL.Keywords: Breast cancer; chemotherapy-induced nausea and vomiting; single nucleotide polymorphism.
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| 7. |
- Shamoun, Levar, et al.
(författare)
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Association of gene and protein expression and genetic polymorphism of CC chemokine ligand 4 in colorectal cancer
- 2021
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Ingår i: World Journal of Gastroenterology. - : Baishideng Publishing Group. - 1007-9327 .- 2219-2840. ; 27:30, s. 5076-5087
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Leukocytes, such as T cells and macrophages, play an important role in tumorigenesis. CC chemokine ligand (CCL) 4, which is produced by lymphocytes and macrophages, has been found to be expressed in the mucosa of the gastrointestinal tract and is a potent chemoattractant for various leukocytes. AIM To examine CCL4 expression and its genetic polymorphism rs10491121 in patients with colorectal cancer (CRC) and evaluate their prognostic significance. METHODS Luminex technology was used to determine CCL4 Levels in CRC tissue (n = 98), compared with paired normal tissue, and in plasma from patients with CRC (n = 103), compared with healthy controls (n = 97). Included patients had undergone surgical resection for primary colorectal adenocarcinomas between 1996 and 2019 at the Department of Surgery, Ryhov County Hospital, Jönköping, Sweden. Reverse transcription quantitative PCR was used to investigate the CCL4 gene expression in CRC tissue (n = 101). Paired normal tissue and TaqMan single nucleotide polymorphism assays were used for the CCL4 rs10491121 polymorphism in 610 CRC patients and 409 healthy controls. RESULTS The CCL4 protein and messenger RNA expression levels were higher in CRC tissue than in normal paired tissue (90%, P < 0.001 and 45%, P < 0.05, respectively). CRC tissue from patients with localized disease had 2.8-fold higher protein expression levels than that from patients with disseminated disease. Low CCL4 protein expression levels in CRC tissue were associated with a 30% lower cancer-specific survival rate in patients (P < 0.01). The level of plasma CCL4 was 11% higher in CRC patients than in healthy controls (P < 0.05) and was positively correlated (r = 0.56, P < 0.01) with the CCL4 protein level in CRC tissue. The analysis of CCL4 gene polymorphism rs10491121 showed a difference (P < 0.05) between localized disease and disseminated disease in the right colon, with a dominance of allele A in localized disease. Moreover, the rate of the A allele was higher among CRC patients with mucinous cancer than among those with nonmucinous cancer. CONCLUSION The present study indicates that the CRC tissue levels of CCL4 and CCL4 gene polymorphism rs10491121, particularly in the right colon, are associated with clinical outcome in CRC patients.
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| 8. |
- Shamoun, Levar, et al.
(författare)
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Association study on IL-4, IL-4Rα and IL-13 genetic polymorphisms in Swedish patients with colorectal cancer
- 2018
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Ingår i: Clinica Chimica Acta. - : Elsevier. - 0009-8981 .- 1873-3492. ; 487, s. 101-106
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Interleukin 4 (IL-4) and interleukin 13 (IL-13) are anti-inflammatory and immunomodulatory cytokines which share a common cellular receptor IL4Rα and are involved in the same signaling pathways. Our purpose was to assess whether genetic variants within IL-4, IL-13 and IL-4Rα are associated with the risk or clinical outcome of colorectal cancer (CRC).METHODS: Three single nucleotide polymorphisms (SNPs) were screened in 466 patients with CRC and 445 healthy controls. The selected SNPs were IL-4 SNP rs2243250, IL-4Rα SNP rs1801275 and IL-13 SNP rs1800925.RESULTS: We found that the genotype variant T/T in IL-13 gene was associated with a higher risk of CRC. Kaplan-Meier analysis showed that the cancer specific survival differed between C/C and CT + TT for IL-4 SNP. Moreover, the carriers of the T allele were associated with the highest risk of CRC death with a hazard ratio (HR) of 1.57, 95% CI 1.06-2.36, p = .024. The observed effect of the T allele was restricted to stage III patients.CONCLUSION: Our results indicate IL-13 SNP rs1800925 as a risk factor for CRC and that IL-4 SNP rs2243250 could be a useful prognostic marker in the follow-up and clinical management of patients with CRC especially in stage III disease.
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| 9. |
- Shamoun, Levar, et al.
(författare)
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Protein expression and genetic variation of IL32 and association with colorectal cancer in Swedish patients
- 2018
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 38:1, s. 321-328
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Tidskriftsartikel (refereegranskat)abstract
- Background: Interleukin 32 (IL32) is an intracellular pluripotent cytokine produced by epithelial cells, monocytes, T-lymphocytes and natural killer cells and seems to be involved in the pathogenesis of cancer and inflammatory diseases. Our purpose was to assess the role of protein expression and genetic polymorphisms of IL32 in colorectal cancer (CRC) susceptibility.Materials and Methods: To gain insight into clinical significance of IL32 in Swedish patients with CRC, using enzyme-linked immunosorbent assay, we determined whether IL32 protein level is altered in CRC tissue (n=75) compared with paired normal tissue and in plasma from patients with CRC (n=94) compared with controls (n=81). The expression of IL32 protein was confirmed by immunohistochemistry (n=73). We used Luminex technology to investigate protein levels of the cytokines IL6, tumor necrosis factor-a (TNFa) and vascular endothelial growth factor (VEGF) to relate these to IL32 levels in CRC tissue. Three single nucleotide polymorphisms (SNPs) (rs28372698, rs12934561, rs4786370) of the IL32 gene have been proposed as modifiers for different diseases. The present study evaluated the susceptibility of patients possessing these SNPs to CRC. Using TaqMan SNP genotyping assays, these SNPs were screened in Swedish patients with CRC (n=465) and healthy controls (n=331).Results: We found no significant differences in the genotypic frequencies between the patients and healthy controls and no relation to survival for any of the SNPs. However, the SNP rs12934561 was statisticalLY significant associated with older patients. IL32 protein was up-regulated in CRC tissue and related to IL6, TNFa, and VEGF, and seems to be modulated by SNP rs28372698. The IL32 protein level in CRC tissue also reflects both disseminated disease and location. Conclusion. Our results suggest that altered IL32 protein concentrations in CRC tissue and genotypic variants of IL32 are related to disseminated CRC.
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| 10. |
- Van Nguyen, Song, et al.
(författare)
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Cytotoxic T-lymphocyte antigen-4 (CTLA-4) gene polymorphism (rs3087243) is related to risk and survival in patients with colorectal cancer
- 2021
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Ingår i: In Vivo. - : International Institute of Anticancer Research. - 0258-851X .- 1791-7549. ; 35:2, s. 969-975
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIM: Cytotoxic T-lymphocyte antigen-4 (CTLA-4), transiently expressed on T cells, plays a pivotal role in the negative feedback regulation of T-cell activation and proliferation. The aim of the present study was to examine the influence of CTLA-4 gene polymorphism rs3087243 on CRC susceptibility and long-term survival in Swedish patients with CRC.PATIENTS AND METHODS: Genotypes of 491 patients and 433 healthy controls were determined, using TaqMan single nucleotide polymorphism (SNP) assays based on polymerase chain reaction.RESULTS: Patients carrying allele A were found to be at a higher risk of CRC and this allele was found to be more common in patients with disseminated disease compared to localized disease in the right colon. Kaplan-Meier analysis of cancer-specific survival showed that carriers of allele A had the highest risk of CRC-related death.CONCLUSION: The SNP rs3087243 of the CTLA-4 gene was associated with CRC risk and, therefore, it could be a prognostic marker for Swedish patients with CRC.
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