Guidelines for the standardized diagnosis and treatment of non-specific orbital inflammation(2024)

Non-specific orbital inflammation(NSOI)is a noninfectious orbital inflammation.Although it is often considered the most common diagnosis in orbital biopsies,it is an exclusionary diagnosis that requires ruling out systemic disease or other possible causes.Its characteristics include acute orbital signs and symptoms,including pain,proptosis,periorbital edema,chemosis,diplopia,and visual impairment.The clinical manifestations and histological findings of NSOI are heterogeneous,without specific diagnostic criteria or treatment guidelines,which poses significant challenges for diagnosis and treatment.This guideline provides a detailed description of the definition,classification,diagnosis,and treatment of NSOI.

Influence of reduced-port laparoscopic surgery on perioperative indicators, postoperative recovery, and serum inflammation in patients with colorectal carcinoma

BACKGROUND Conventional five-port laparoscopic surgery,the current standard treatment for colorectal carcinoma(CRC),has many disadvantages.AIM To assess the influence of reduced-port laparoscopic surgery(RPLS)on perioperative indicators,postoperative recovery,and serum inflammation indexes in patients with CRC.METHODS The study included 115 patients with CRC admitted between December 2019 and May 2023,52 of whom underwent conventional five-port laparoscopic surgery(control group)and 63 of whom underwent RPLS(research group).Comparative analyses were performed on the following dimensions:Perioperative indicators[operation time(OT),incision length,intraoperative blood loss(IBL),and rate of conversion to laparotomy],postoperative recovery(first postoperative exhaust,bowel movement and oral food intake,and bowel sound recovery time),serum inflammation indexes[high-sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)],postoperative complications(anastomotic leakage,incisional infection,bleeding,ileus),and therapeutic efficacy.RESULTS The two groups had comparable OTs and IBL volumes.However,the research group had a smaller incision length;lower rates of conversion to laparotomy and postoperative total complication;and shorter time of first postoperative exhaust,bowel movement,oral food intake,and bowel sound recovery;all of which were significant.Furthermore,hs-CRP,IL-6,and TNF-αlevels in the research group were significantly lower than the baseline and those of the control group,and the total effective rate was higher.CONCLUSION RPLS exhibited significant therapeutic efficacy in CRC,resulting in a shorter incision length and a lower conversion rate to laparotomy,while also promoting postoperative recovery,effectively inhibiting the inflammatory response,and reducing the risk of postoperative complications.

Are preoperative inflammatory and nutritional markers important for the prognosis of patients with peritoneal metastasis of colorectal cancer?

Colorectal cancer(CRC)is a type of cancer that grows from polypoid lesions developing over the years.It has a high incidence of about 1.8 million new cases annually.While screening and lifestyle modifications have stabilized the rate of CRC in high-income countries,the incidence of early-onset CRC is increasing globally.The worst prognosis for this cancer is linked to recurrence and metastasis,with peritoneal metastasis occurring in 8%to 20%of cases.In these cases,treatment with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is indicated.However,this approach is risky and requires careful selection of patients who will truly benefit from it.This article will discuss the correlation between nutrition and inflammation in patients with peritoneal metastasis and advanced CRC,emphasizing the importance of nutritional and inflammatory markers for assessing disease status.Finally,we will highlight the main biomarkers in the field.

Systemic inflammation in colorectal cancer: Underlying factors,effects, and prognostic significance

Systemic inflammation is a marker of poor prognosis preoperatively present in around 20%-40%of colorectal cancer patients.The hallmarks of systemic inflammation include an increased production of proinflammatory cytokines and acute phase proteins that enter the circulation.While the low-level systemic inflammation is often clinically silent,its consequences are many and may ultimately lead to chronic cancer-associated wasting,cachexia.In this review,we discuss the pathogenesis of cancer-related systemic inflammation,explore the role of systemic inflammation in promoting cancer growth,escaping antitumor defense,and shifting metabolic pathways,and how these changes are related to less favorable outcome.

Inflammation and colorectal cancer, when microbiota-host mutualism breaks

Structural changes in the gut microbial community have been shown to accompany the progressive development of colorectal cancer.In this review we discuss recent hypotheses on the mechanisms involved in the bacteria-mediated carcinogenesis,as well as the triggering factors favoring the shift of the gut microbiota from a mutualistic to a pro-carcinogenic configuration.The possible role of inflammation,bacterial toxins and toxic microbiota metabolites in colorectal cancer onset is specifically discussed.On the other hand,the strategic role of inflammation as the keystone factor in driving microbiota to become carcinogenic is suggested.As a common outcome of different environmental and endogenous triggers,such as diet,aging,pathogen infection or genetic predisposition,inflammation can compromise the microbiota-host mutualism,forcing the increase of pathobionts at the expense of health-promoting groups,and allowing the microbiota to acquire an overall pro-inflammatory configuration.Consolidating inflammation in the gut,and favoring the bloom of toxigenic bacterial drivers,these changes in the gut microbial ecosystem have been suggested as pivotal in promoting carcinogenesis.In this context,it will become of primary importance to implement dietary or probiotics-based interventions aimed at preserving the microbiota-host mutualism along aging,counteracting deviations that favor a pro-carcinogenic microbiota asset.

Role of epigenetics in transformation of inflammation into colorectal cancer

Molecular mechanisms associated with inflammation-promoted tumorigenesis have become an important topic in cancer research. Various abnormal epigenetic changes, including DNA methylation, histone modification, chromatin remodeling, and noncoding RNA regulation, occur during the transformation of chronic inflammation into colorectal cancer(CRC). These changes not only accelerate transformation but also lead to cancer progression and metastasis by activating carcinogenic signaling pathways. The NF-κB and STAT3 signaling pathways play a particularly important role in the transformation of inflammation into CRC, and both are critical to cellular signal transduction and constantly activated in cancer by various abnormal changes including epigenetics. The NF-κB and STAT3 signals contribute to the microenvironment for tumorigenesis through secretion of a large number of pro-inflammatory cytokines and their crosstalk in the nucleus makes it even more difficult to treat CRC. Compared with gene mutation that is irreversible, epigenetic inheritance is reversible or can be altered by the intervention. Therefore, understanding the role of epigenetic inheritance in the inflammation-cancer transformation may elucidate the pathogenesis of CRC and promote the development of innovative drugs targeting transformation to prevent and treat this malignancy. This review summarizes the literature on the roles of epigenetic mechanisms in the occurrence and development of inflammation-induced CRC. Exploring the role of epigenetics in the transformation of inflammation into CRC may help stimulate futures studies on the role of molecular therapy in CRC.

Comparison of selected inflammation-based prognostic markers in relapsed or refractory metastatic colorectal cancer patients

AIM: To investigate the impact of systemic inflammationbased prognostic markers on overall survival in relapsed/refractory metastatic colorectal cancer(m CRC) patients. METHODS: To investigate prognostic markers in m CRC patients,this study was performed with patients who have experienced relapsed/refractory m CRC with standard chemotherapy or were inapplicable to conventional treatment modality because of poor performance status,age,or comorbidity. We reviewed the medical records of 177 m CRC patients managed with Korean Medicine(KM) treatment modality using an anticancer agent of Rhus verniciflua Stokes extract from June 2006 to April 2013. The clinicopathologic characteristics,laboratory test,the systemic inflammation markers including the modified Glasgow prognostic score(m GPS),neutrophil lymphocyte ratio(NLR),platelet lymphocyte ratio(PLR),lymphocyte monocyte ratio(LMR),and prognostic nutritional index(PNI) were analyzed. The overall survival of patients was calculated with the Kaplan-Meier method and the statistical significance was compared using with the log-rank test. To compare the impact of systemic inflammation based markers,the hazard ratio(HR) of m GPS,NLR,PLR,LMR,and PNI for overall survival were evaluated with the Cox proportional hazards regression.RESULTS: The majority of m CRC patients had relapsed/refractory to standard chemotherapy; 128 patients(72.3%) had undergone more than second line chemotherapy,and the median time from diagnosis of m CRC to initiation of KM was 9.4 mo. The median overall survival of enrolled patients was 8.3 mo. On univariate analyses,the inflammation markers of higher m GPS(P < 0.001),NLR ≥ 5(P < 0.001),PLR > 300(P = 0.004),LMR ≤ 3.4(P < 0.001),and PNI ≤ 45.3(P = 0.001) were significantly associated with decreased survival time. On stepwise multivariate proportional hazards model,m GPS at 2 vs 0(HR = 3.212,95%CI: 1.437-7.716,P = 0.004),and LMR ≤ 3.4(HR = 1.658,95%CI: 1.092-2.518,P = 0.018) as independent predictors associated with poor overall survival along with carbohydrate antigen 19-9(HR = 1.482,95%CI: 1.007-2.182,P = 0.046),AST ≥ 40(HR = 2.377,95%CI: 1.359-4.155,P = 0.002),and the treatment duration for KM less than 2.9 mo(HR = 1.718,95%CI: 1.160-2.543,P = 0.007).CONCLUSION: These results indicate that the inflammatory markers,m GPS and LMR are independent prognostic factors for predicting overall survival in relapsed/refractory m CRC patients.

Intestinal inflammation and colorectal cancer:A doubleedged sword?

Chronic inflammation is thought to be the leading cause of many human cancers including colorectal cancer(CRC).Accordingly,epidemiologic and clinical studies indicate that patients affected by ulcerative colitis and Crohn's disease,the two major forms of inflammatory bowel disease,have an increased risk of developing CRC.In recent years,the role of immune cells and their products have been shown to be pivotal in initiation and progression of colitis-associated CRC.On the other hand,activation of the immune system has been shown to cause dysplastic cell elimination and cancer suppression in other settings.Clinical and experimental data herein reviewed,while confirming chronic inflammation as a risk factor for colon carcinogenesis,do not completely rule out the possibility that under certain conditions the chronic activation of the mucosal immune system might protect from colonic dysplasia.

Inflammation-associated microsatellite alterations:Mechanisms and significance in the prognosis of patients with colorectal cancer

Microsatellite alterations within genomic DNA frameshift as a result of defective DNA mismatch repair(MMR). About 15% of sporadic colorectal cancers(CRCs) manifest hypermethylation of the DNA MMR gene MLH1, resulting in mono-and di-nucleotide frameshifts to classify it as microsatellite instability-high(MSI-H) and hypermutated, and due to frameshifts at coding microsatellites generating neo-antigens, produce a robust protective immune response that can be enhanced with immune checkpoint blockade. More commonly, approximately 50% of sporadic nonMSI-H CRCs demonstrate frameshifts at di-and tetra-nucleotide microsatellites to classify it as MSIlow/elevated microsatellite alterations at selected tetranucleotide repeats(EMAST) as a result of functional somatic inactivation of the DNA MMR protein MSH3 via a nuclear-to-cytosolic displacement. The trigger for MSH3 displacement appears to be inflammation and/or oxidative stress, and unlike MSI-H CRC patients, patients with MSI-L/EMAST CRCs show poor prognosis. These inflammatory-associated microsatellite alterations are a consequence of the local tumor microenvironment, and in theory, if the microenvironment is manipulated to lower inflammation, the microsatellite alterations and MSH3 dysfunction should be corrected. Here we describe the mechanisms and significance of inflammatory-associated microsatellite alterations, and propose three areas to deeply explore the consequences and prevention of inflammation's effect upon the DNA MMR system.

Predictive Values of Postoperative and Dynamic Changes of Inflammation Indexes in Survival of Patients with Resected Colorectal Cancer

The aim of the present study was to evaluate the prognostic potential of postoperative scores of inflammation indexes and the dynamic changes of scores before and after tumor resection in colorectal cancer patients.The study included 516 colorectal cancer patients with primary colorectal tumor resection.Cox regression was applied to estimate the associations of postoperative and dynamic changes of inflammation indexes with progression-free survival and overall survival.As results,we found that higher postoperative neutrophil to lymphocyte ratio (NLR),neutrophil and monocyte to lymphocyte ratio (NMLR),platelet to lymphocyte ratio (PLR) and systemic immune inflammation index (SII)were associated with shorter progression-free survival.The increased NLR,NMLR,PLR,SII and C-reaction protein (CRP)to albumin (ALB) ratio (CAR)were associated with poor progression-free survival,with HRs (95% CIs)of 1.92 (1.27-2.90),1.46(1.11-2.09),2.10(1.34-3.30),1.81(1.22-2.70)and 1.65(1.03-2.67), respectively.Postoperative NMLR,SII,CAR,and their dynamic changes were also significantly correlated with overall survival,with the HRs (95% CIs)of 2.63(1.30-3.97), 2.44(1.43-4.17),2.74(1.31-5.74),2.08(1.21-3.60),1.97(1.12-3.45)and 2.55(1.21-5.38)respectively.In conclusion,postoperative inflammation indexes and their dynamic changes,particularly for NMLR,SII and CAR are promising prognostic predictors of CRC patients.

Plecanatide-mediated activation of guanylate cyclase-C suppresses inflammation-induced colorectal carcinogenesis in Apc+/Min-FCCC mice

AIM To evaluate the effect of orally administered plecanatide on colorectal dysplasia in Apc^(+/Min-FCCC) mice with dextran sodium sulfate(DSS)-induced inflammation. METHODS Inflammation driven colorectal carcinogenesis was induced in Apc^(+/Min-FCCC) mice by administering DSS in their drinking water. Mice were fed a diet supplemented with plecanatide(0-20 ppm) and its effect on the multiplicity of histopathologically confirmed polypoid,flat and indeterminate dysplasia was evaluated. Plecanatide-mediated activation of guanylate cyclase-C(GC-C) signaling was assessed in colon tissues by measuring cyclic guanosine monophosphate(cG MP) by ELISA, protein kinase G-II and vasodilator stimulated phosphoprotein by immunoblotting. Ki-67, c-myc and cyclin D1 were used as markers of proliferation. Cellular levels and localization of b-catenin in colon tissues were assessed by immunoblotting and immunohistochemistry, respectively. Uroguanylin(UG) and GC-C transcript levels were measured by quantitative reverse transcription polymerase chain reaction(RT-PCR). A mouse cytokine array panel was used to detect cytokines in the supernatant of colon explant cultures. RESULTS Oral treatment of Apc^(+/Min-FCCC) mice with plecanatide produced a statistically significant reduction in the formation of inflammation-driven polypoid, flat and indeterminate dysplasias. This anti-carcinogenic activity of plecanatide was accompanied by activation of cG MP/GC-C signaling mediated inhibition of Wnt/b-catenin signaling and reduced proliferation. Plecanatide also decreased secretion of pro-inflammatory cytokines(IL-6, IL-1 TNF), chemokines(MIP-1, IP-10) and growth factors(GCSF and GMCSF) from colon explants derived from mice with acute DSS-induced inflammation. The effect of plecanatidemediated inhibition of inflammation/dysplasia on endogenous expression of UG and GC-C transcripts was measured in intestinal tissues. Although GC-C expression was not altered appreciably, a statistically significant increase in the level of UG transcripts was detected in the proximal small intestine and colon, potentially due to a reduction in intestinal inflammation and/or neoplasia. Taken together, these results suggest that reductions in endogenous UG, accompanied by dysregulation in GC-C signaling, may be an early event in inflammation-promoted colorectal neoplasia; an event that can potentially be ameliorated by prophylactic intervention with plecanatide.CONCLUSION This study provides the first evidence that orally administered plecanatide reduces the multiplicity of inflammation-driven colonic dysplasia in mice, demonstrating the utility for developing GC-C agonists as chemopreventive agents.

Cysteinyl leukotrienes and their receptors: Bridging inflammation and colorectal cancer

Long-standing inflammation has emerged as a hallmark of neoplastic transformation of epithelial cells and may be a limiting factor of successful conventional tumor therapies.A complex milieu composed of distinct stromal and immune cells,soluble factors and inflammatory mediators plays a crucial role in supporting and promoting various types of cancers.An augmented inflammatory response can predispose a patient to colorectal cancer(CRC).Common risk factors associated with CRC development include diet and lifestyle,altered intestinal microbiota and commensals,and chronic inflammatory bowel diseases.Cysteinyl leukotrienes are potent inflammatory metabolites synthesized from arachidonic acid and have a broad range of functions involved in the etiology of various pathologies.This review discusses the important role of cysteinyl leukotriene signaling in linking inflammation and CRC.

STAT3 and sphingosine-1-phosphate in inflammation-associated colorectal cancer

Accumulated evidences have demonstrated that signal transducer and activator of transcription 3(STAT3)is a critical link between inflammation and cancer.Multiple studies have indicated that persistent activation of STAT3 in epithelial/tumor cells in inflammation-associated colorectal cancer(CRC)is associated with sphingosine-1-phosphate(S1P)receptor signaling.In inflammatory response whereby interleukin(IL)-6 production is abundant,STAT3-mediated pathways were found to promote the activation of sphingosine kinases(SphK1and SphK2)leading to the production of S1P.Reciprocally,S1P encourages the activation of STAT3 through a positive autocrine-loop signaling.The crosstalk between IL-6,STAT3 and sphingolipid regulated pathways may play an essential role in tumorigenesis and tumor progression in inflamed intestines.Therapeutics targeting both STAT3 and sphingolipid are therefore likely to contribute novel and more effective therapeutic strategies against inflammation-associated CRC.

Inflammation,microbiome and colorectal cancer disparity in African-Americans:Are there bugs in the genetics?

Dysregulated interactions between host inflammation and gut microbiota over the course of life increase the risk of colorectal cancer(CRC).While environmental factors and socio-economic realities of race remain predominant contributors to CRC disparities in African-Americans(AAs),this review focuses on the biological mediators of CRC disparity,namely the under-appreciated influence of inherited ancestral genetic regulation on mucosal innate immunity and its interaction with the microbiome.There remains a poor understanding of mechanisms linking immune-related genetic polymorphisms and microbiome diversity that could influence chronic inflammation and exacerbate CRC disparities in AAs.A better understanding of the relationship between host genetics,bacteria,and CRC pathogenesis will improve the prediction of cancer risk across race/ethnicity groups overall.

Protective effect of notoginsenoside and tanshinone IIA on inflammation-related colorectal cancer mice and the inhibition effect on COX-2 expression

Objective To explore the preventive effects and possible mechanisms of action of notoginsenoside(NGS)and tanshinone IIA(TSN)in inflammation-related colorectal cancer(IRCC)in mice.Methods Eighty-eight male C57BL/6 mice were randomly assigned to 11 groups(n=8 each group).Azomethane oxide+dextran sulfate(AOM+DSS)model control(model),NGS lowdose(l-NGS),NGS medium-dose(m-NGS),NGS high-dose(h-NGS),TSN low-dose(l-TSN),TSN medium-dose(m-TSN),TSN high-dose(h-TSN),(NGS+TSN)low-dose[l-(NGS+TSN)],(NGS+TSN)medium-dose[m-(NGS+TSN)],(NGS+TSN)high-dose[h-(NGS+TSN)],and blank groups were established.The first 10 groups were intraperitoneally injected with AOM to induce inflammatory colon cancer,whereas the blank group was intraperitoneally injected with 0.9%NaCl solution.The first 10 groups drank a 2.5%sodium DSS aqueous solution continuously from day 5 for three cycles(one cycle:five days,every three weeks),and the blank group was allowed free access to water.Drug groups were administered NGS(low,medium,or high dose),TSN(low,medium,or high dose),or NGS+TSN(low,medium,or high dose),and the model and blank groups were administered saline by lavage until the end of the experiment.The general activity,body weight,and survival rate of and incidence of adenocarcinoma in mice were detected and the expression of cyclooxygenase 2(COX-2)was detected by immunohistochemistry.Results(1)The survival rate of mice with IRCC in the h-NGS,m-TSN,h-TSN,m-(NGS+TSN),and h-(NGS+TSN)groups was significantly increased than that in other groups(P<0.05).(2)The incidence of tumors in the h-(NGS+TSN),m-TSN,and l-NGS groups was significantly lower than that in the model group(P<0.05).(3)The expression level of COX-2 in tumor tissues of mice in the m-(NGS+TSN)and h-(NGS+TSN)groups was significantly lower than that in the model group(P<0.05).Conclusion Tumor formation was inhibited by m-TSN and h-(NGS+TSN)treatments in mice with IRCC,and h-(NGS+TSN)treatment inhibited the COX-2 pathway.

Inflammation-based factors and prognosis in patients with colorectal cancer

Several parameters for predicting survival in patients with colorectal cancer have been identified, including the performance status, age, gender and tumor-nodemetastasis(TNM) stage. Although the TNM stage is important and useful for predicting the prognosis and determining the appropriate treatment, it is well known that the survival time varies widely, even in patients with the same stage of disease. Therefore, the identification of new parameters capable of more precisely predicting patient survival is needed to help select the optimal treatment, especially in patients in the advanced stage of disease. Although the TNM stage reflects the tumor characteristics, cancer progression and survival are not determined solely based on the local characteristics of the tumor, but also the host systemic immune/inflammatory response. Therefore, using a combination of parameters that reflect both tumor characteristics and the host systemic inflammatory status is thought to be important for accurately predicting patient survival.

Hyperhomocysteinemia as a potential contributor of colorectal cancer development in inflammatory bowel diseases: A review

Homocysteine is an amino acid generated metabolically by the S-adenosylmethionine-dependent transmethylation pathway. In addition to being a well-known independent risk factor for coronary heart disease, is also a risk factor for cancer. Patients suffering from inflammatory bowel diseases(IBD) including ulcerative colitis and Crohn's disease are at increased risk of developing colorectal cancer in comparison to healthy individuals. Furthermore, the risk of hyperhomocysteinaemia is significantly higher in IBD patients when compared with controls. In the present article, we review the mechanisms in which hyperhomocysteinemia may contribute to increased risk of colorectal cancer in IBD patients.

Relationship between Fusobacterium nucleatum,inflammatory mediators and microRNAs in colorectal carcinogenesis

AIM To examine the effect of Fusobacterium nucleatum(F. nucleatum) on the microenvironment of colonic neoplasms and the expression of inflammatory mediators and microRNAs(miRNAs).METHODS Levels of F. nucleatum DNA, cytokine gene mRNA(TLR2, TLR4, NFKB1, TNF, IL1 B, IL6 and IL8), and potentially interacting miRNAs(miR-21-3p, miR-22-3p, mi R-28-5p, miR-34a-5p, miR-135b-5p) were measured by quantitative polymerase chain reaction(qPCR) TaqMan? assays in DNA and/or RNA extracted from the disease and adjacent normal fresh tissues of 27 colorectal adenoma(CRA) and 43 colorectal cancer(CRC) patients. KRAS mutations were detected by direct sequencing and microsatellite instability(MSI) status by multiplex PCR. Cytoscape v3.1.1 was used to construct the postulated miRNA:mRNA interaction network.RESULTS Overabundance of F. nucleatum in neoplastic tissue compared to matched normal tissue was detected in CRA(51.8%) and more markedly in CRC(72.1%). We observed significantly greater expression of TLR4, IL1 B, IL8, and miR-135 b in CRA lesions and TLR2, IL1 B, IL6, IL8, mi R-34 a and miR-135 b in CRC tumours compared to their respective normal tissues. Only two transcripts for miR-22 and miR-28 were exclusively downregulated in CRC tumour samples. The mRNA expression of IL1 B, IL6, IL8 and miR-22 was positively correlated with F. nucleatum quantification in CRC tumours. The mRNA expression of miR-135 b and TNF was inversely correlated. The miRNA:mRNA interaction network suggested that the upregulation of miR-34 a in CRC proceeds via a TLR2/TLR4-dependent response to F. nucleatum. Finally, KRAS mutations were more frequently observed in CRC samples infected with F. nucleatum and were associated with greater expression of miR-21 in CRA, while IL8 was upregulated in MSI-high CRC.CONCLUSION Our findings indicate that F. nucleatum is a risk factor for CRC by increasing the expression of inflammatory mediators through a possible mi RNA-mediated activation of TLR2/TLR4.

Inflammatory pathways in the early steps of colorectal cancer development

Colorectal cancer is a major cause of cancer-related death in many countries.Colorectal carcinogenesis is a stepwise process which,from normal mucosa leads to malignancy.Many factors have been shown to influence this process,however,at present,several points remain obscure.In recent years some hypotheses have been considered on the mechanisms involved in cancer development,expecially in its early stages.Tissue injury resulting from infectious,mechanical,or chemical agents may elicit a chronic immune response resulting in cellular proliferation and regeneration.Chronic inflammation of the large bowel(as in inflammatory bowel diseases),has been associated with the subsequent development of colorectal cancer.In this review we examine the inflammatory pathways involved in the early steps of carcinogenesis,with particular emphasis on colorectal.Firstly,we describe cells and proteins recently suggested as central in the mechanism leading to tumor development.Macrophages and neutrophils are among the cells mostly involved in these processes and proteins,as cyclooxygenases and resolvins,are crucial in these inflammatory pathways.Indeed,the activation of these pathways establishes an oxidative and anaerobic microenvironment with DNA damage to epithelial cells,and shifting from an aerobic to an anaerobic metabolism.Many cellular mechanisms,such as proliferation,apoptosis,and autophagy are altered causing failure to control normal mucosa repair and renewal.

Relation between common polymorphisms in genes related to inflammatory response and colorectal cancer

AIM： To investigate the association between common single nucleotide polymorphisms （SNPs） in inflammatory response-related genes such as interleukin （IL）-6, IL-8, tumor necrosis factor α （TNFα）, peroxisome proliferators-activated receptor γ （PPARγ）, intercellular adhesion molecule-1 （ICAM-1） and the risk of colorectal cancer （CRC） in a group of Greek patients. METHODS： The study group consisted of 222 CRC patients and 200 healthy controls. Genotyping was performed using allele-specific PCR of PRC-RFLP and the results were confirmed by sequencing. We studied the association of SNPs in the IL-6 （-174G 〉 C）, IL-8 （-251T 〉 A）, TNFα （-308G 〉 A）, ICAM-1 （R241G and K469E）, and PPARγ （Pro12Ala） genes and the risk of CRC. RESULTS： The IL-6 -174G, R241 and K469 alleles of ICAM-1 were associated with increased risk of CRC （OR = 1.77, 95% CI： 1.34-2.34; OR = 1.83, 95% CI： 1.23-2.72; and OR = 1.35, 95% CI： 1.03-1.77 respectively）. The IL-8 and TNFα polymorphisms had no effect. Whereas the PPARγ Pro12 genotype was associated with increased risk of disease （OR = 1.78, 95% CI： 1.25-2.49）. CONCLUSION： The association between common SNPs in immunologic response-related genes and CRC is reported in the present study. Apart from shedding light on the mechanisms of malignancy initiation and progression, SNPs may improve appropriate screening for sub-populations at risk.