scholarly journals Relationship between Arg753Gln Toll-like receptor 2 and Asp299Gly Toll-like receptor 4 genetic variations and susceptibility to colorectal cancer in Southern Iran

2018 ◽  
Vol 70 (4) ◽  
pp. 775-779 ◽  
Author(s):  
Seyed Hosseini ◽  
Zahra Mojtahedi ◽  
Zahra Beizavi ◽  
Hajar Khazraei ◽  
Mozhdeh Zamani

Variations in Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) encoding genes have been associated with tumorigenesis through the disruption of immune and inflammatory responses. The aims of this study were to evaluate the two single nucleotide polymorphisms (SNPs) of the genes Arg753Gln TLR2 (rs5743708) and Asp299Gly TLR4 (rs4986790) in colorectal cancer patients in southern Iran. Colorectal cancer patients and healthy controls were included in this study (150 Persian subjects in each group). Blood samples were used for genotyping by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The association between these SNPs and colorectal cancer and clinicopathological factors, including age, gender, tumor stage and differentiation were also investigated. A significant association was found between Arg753Gln TLR2 SNP and colorectal cancer. This SNP was significantly more frequent in male patients. However, there was no association between Asp299Gly TLR4 and colorectal cancer. Therefore, Arg753Gln TLR2 SNP can be considered as a risk factor for colorectal cancer incidence in southern Iran, especially in men. Further investigations in other populations are recommended in order to assess the association of this SNP with colorectal cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3581-3581
Author(s):  
Anita Roselyn Peoples ◽  
Biljana Gigic ◽  
Jennifer Ose ◽  
Andreana Natalie Holowatyj ◽  
Patrick M. Mallea ◽  
...  

3581 Background: Pain is a prevalent, debilitating symptom in more than half of cancer patients. Accumulating evidence suggests a bi-directional relationship between gut microbiota and pain, potentially via inflammation and oxidative stress. Fusobacterium nucleatum (Fn), a pro-inflammatory anaerobic bacterium, is frequently detected in colorectal cancer (CRC) patients. To date, no study has identified a relationship between Fn and cancer pain in CRC patients. We investigated the associations between pre-treatment Fn and cancer pain at 6 months post-surgery in CRC patients. Methods: We utilized pre-surgery stool samples collected from 80 prospectively followed, newly diagnosed CRC patients recruited from the German site of the international ColoCare Study. Eligible patients were neo-adjuvant treatment naïve and did not use antibiotics for at least 1 month before stool collection. Fn DNA was assessed via quantitative real-time polymerase chain reaction. Patients were median split into Fn-high (>17.27; n=40) or Fn-low (≤17.27; n=40). Cancer pain was assessed using the 2 pain symptom items from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core-30 (lower score=lower pain) at pre- and 6 months post-surgery. Results: Before surgery, 48% of all patients reported any pain. At 6 months post-surgery, we observed a decrease in cancer pain by 33% for Fn-low, while there was an increase in cancer pain by 41% for Fn-high. After controlling for pre-surgery cancer pain in ANCOVA model, we observed significantly higher mean cancer pain at 6 months post-surgery in the Fn-high group vs. the Fn-low group (24.07 vs. 13.44; effect size, ES=0.45; p=0.04). These results were maintained even after controlling for age, sex, tumor stage and site, adjuvant chemotherapy, BMI, physical activity, and any pain medications (29.11 vs. 16.55; ES=0.53; p=0.03). Conclusions: These findings suggest that high Fn is an independent predictor of cancer pain at 6 months post-surgery in colorectal cancer patients. Further research is needed to confirm and understand the mechanisms of these results. Funding: NCI U01 CA206110.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 199-199
Author(s):  
Mitsukuni Suenaga ◽  
Wu Zhang ◽  
Tetsuo Mashima ◽  
Marta Schirripa ◽  
Shu Cao ◽  
...  

199 Background: We previously reported that genetic variant in the CCL5/CCR5 pathway predict efficacy of regorafenib in metastatic colorectal cancer patients (mCRC). CCL5 rs2280789 G allele and CCL5 rs3817655 T allele were associated with longer overall survival (OS) and severe skin toxicity due to low VEGF-A production via endothelial progenitor cell (EPC). CCL4 rs1634517 G allele and CCL3 rs1130371 C allele correlated with longer Progression-free survival (PFS) and OS. We investigated the biological role of CCL4 and CCL3 gene polymorphisms. Methods: We analyzed genomic DNA extracted from 79 samples of a Japanese cohort receiving regorafenib. Single nucleotide polymorphisms (SNPs) of genes in CCL5/CCR5 pathway were analyzed by PCR-based direct sequencing. Blood samples were obtained from 57 patients at baseline (BL), day 21 and progressive disease (PD), and serum CCR5, CCR5 ligands (CCL3, CCL4, CCL5) and VEGF-A levels were measured using ELISA. PFS and OS were analyzed using Kaplan-Meier curves and log-rank test. Results: Increased CCL3 levels at PD were associated with longer OS than decreased (12.6 vs 4.8 mos, P = 0.003). Patients with decreased CCL4 levels at day 21 had a trend toward longer PFS and tumor shrinkage. Positive correlation was observed between CCL3 and CCR5 throughout the treatment independent of other ligands (change at day 21: r = 0.426, P = 0.009). There was no significant correlation of CCL3 and CCL4 levels with VEGF-A levels. Patients with the G/G variant in CCL3 rs1130371 had increased CCL3, CCR5 and CCL5 levels at day 21 than any A allele. Similarly, patients with the C/C variant had increased CCL3, CCR5 and CCL5 levels at day 21 compared with those with any A allele. In contrast, both CCL5 rs2280789 G allele and CCL5 rs3817655 T allele were associated with increased CCL3 levels and decreased CCL4 levels at day 21 (P = 0.006, P = 0.043; P = 0.006, P = 0.043). Conclusions: Positive correlation of CCL3, CCR5 and CCL5 impact similarly on CCL3 and CCL4 SNPs, while different manner between CCL3 and CCL4 was found in CCL5 SNPs. This suggests an alternative mechanism of action in the network of CCR5 and the ligands except CCL5-VEGF-A signaling via EPC in mCRC patients receiving regorafenib.


2020 ◽  
Vol 57 (2) ◽  
pp. 131-136
Author(s):  
Marianne Regina Silva Potengy de MELLO ◽  
Silmara Fernandes MOURA ◽  
Camila Drumond MUZI ◽  
Raphael Mendonça GUIMARÃES

ABSTRACT BACKGROUND: Colorectal cancer is the third most common type of cancer in the world and the increased survival of the colorectal cancer population is very significant. Thus, it becomes relevant to study the symptoms associated with the progression of the disease and treatment, for proper clinical management. OBJECTIVE: To describe the clinical and epidemiological profile of colorectal cancer patients and to identify the most prevalent signs and symptoms patterns. METHODS: Cross-sectional study evaluating the prevalence of symptoms in 348 colorectal cancer patients admitted to a referral oncology hospital. We applied MSAS-BR scale and, through factor analysis with principal componente analysys, we performed the grouping of symptoms. RESULTS: There was a predominance of men, aged 60 years or older, married, white, with high school, moderately differentiated tumor, stage III/IV disease, colon cancer and no distant metastasis. The most prevalent symptoms were weight loss (67.53%) and the least prevalent were mouth sores (2.01%). The groupings of symptoms established were “fatigue and psychic symptoms”, “gastrointestinal symptoms”, “self-perceptive symptoms” and “general symptoms”, which described 80% of the symptoms presented. CONCLUSION: We evidenced the importance of identifying these symptoms clusters in order to improve strategies for clinical management in patients with colorectal cancer.


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