Polymorphism In Cancer Patients Research Articles

Prevalence of UGT1A1 polymorphisms in gastrointestinal cancer: A single-institutional retrospective study.

797 Background: UGT1A1 gene polymorphisms are heterogeneously distributed among ethnicities and varying geographical regions. Patients with UGT1A1*6 and UGT1A1*28 polymorphisms have an increased risk of grade 3-4 neutropenia and diarrhea from irinotecan due to poor metabolism. This study evaluated the prevalence of UGT1A1 polymorphisms in the cancer patients in a large tertiary cancer center in the Appalachian region, in order to develop individualized institutional guidelines on the utility of UGT1A1 testing in chemotherapy dose management. Methods: This retrospective study evaluated all patients with gastrointestinal (GI) malignancies who underwent UGT1A1 testing prior to chemotherapy initiation between 1/1/2020 and 6/30/2022 at West Virginia University. All patients within this disease sub-specialty who were eligible for chemotherapy were tested for UGT1A1 *6 and UTG1A1*28 polymorphism via PCR based pharmacogenomic evaluation using OneOme RightMed comprehensive testing. Patients were excluded if they were tested for genetic alterations specifically due to previous treatment intolerances. Prevalence of the alterations along with demographic characteristics of patients are reported. Results: UGT1A1 genotyping was performed in 278 patients prior to initiating chemotherapy and 12 patients were excluded due to insufficient sample. A total of 266 patients met the inclusion criteria. The median age was 66 years (IQR: 26-92). Males constituted a higher proportion of the population compared to females (M: F = 147: 119). Colon (n-81; 30.5%) and pancreatic (n-80; 30%) cancers were the predominant GI malignancies. Fifty five percentage of patients (n-146) had metastatic disease. The distribution of the UGT1A1 variant genotype is showed in the table below. Conclusions: The prevalence of heterozygous and homozygous of UGT1A1*28 polymorphism in GI cancer patients in the Appalachian region is 51.5%, consistent with the reported literature. Homozygous and heterozygous UGT1A1 *28 alterations constituted 13.2 and 38.3% respectively. Data collection for pre-emptive chemotherapy dosage adjustments and adverse events is ongoing to integrate testing for UGT1A1 polymorphism routinely for all GI malignancies cancer patients starting irinotecan chemotherapy.[Table: see text]

Pharmacogenetics findings in Brazilian cancer patients.

e13607 Background: Pharmacogenetic is the study of genetic modifications influence on drugs action. Recent studies have suggested that some genetic polymorphisms may have an influence on patient outcomes. Thus, the objective of this thesis is to evaluate the frequency of genetic polymorphisms in cancer patients. Methods: Cross-sectional study at the Oncology Center of São Paulo. The reports presented a SNP evaluation (saliva - PCR-Multiplex, PCR-RFLP or capillary sequencing - Genotypic variants: 1 allele, 2 alleles and no allelic alteration). Polymorphs were validated according to the localized gene and its relationship to drugs using PharmGKB, NCBI SNP Database, NCBI Gene Database and DrugBank Database. Results: Sample mean aging was 49.92 years (SD = 22.73), with breast cancer (n = 26 /% = 26.3) and stage IV (n = 51 /% = 51.6). Among the evaluated platinum components, it is possible to verify that the presence of polymorphisms was more frequent. Of these, all had the highest frequency of polymorphisms in only 1 allele (xpc__rs2228001 = 25.4%; ercc1_rs11615 = 21.2%; xrcc3_rs861539 = 22.2%; mthfr_rs1801133 = 44.4%). This was repeated when evaluating the Cyclophosphamide, Fluoropyrimidines, Taxanes, Anastrozole and Epirubicin-related polymorphisms. When we evaluated the Tamoxifen-related genes, the polymorphisms absence was more frequent (cyp2d6_rs3892097 = 26.3%; cyp3a4_rs2740574 = 61.6%). Evaluating all medications the highest frequency was polymorphism in only 1 allele. Consequently, for the irinotecan drug evaluation, two polymorphisms were evaluated and presence of polymorphism (xrcc3_rs861539 = 58%), mostly in only 1 allele (44%). Conclusions: Therefore we can evaluate that the allelic frequency variability of the polymorphs observed, despite the great variability, shows most evaluated individuals present some type of genotypic modification, being the majority in only 1 allele.

Prevalence of UGT1A1*93 and ABCC5 Polymorphisms in Cancer Patients Receiving Irinotecan-Based Chemotherapy at Al-Najaf Al-Ashraf

Irinotecan (CPT-11) is a semisynthetic derivative of the antineoplastic agent camptothecin used in a wide range as an anti-cancer agent in many solid tumors because of its cytotoxic effect through the interaction with the topoisomerase I enzyme. The major limiting factors for irinotecan treatment are its association with potentially life-threatening toxicities including neutropenia and acute or delayed-type diarrhea, results from distinct interindividual and interethnic variability due to gene polymorphism.
 This is a cross sectional pharmacogentics study was conducted on 25 cancer patients to estimate the prevalence of UGT1A1*93 and ABCC5 allele single nucleotide polymorphism (SNP) in Iraqi cancer patients treated with irinotecan-based therapy at Middle Euphrates Cancer Center. Four drops of venous blood was drawn for each patient and was applied onto the FTA classic card to perform a genotyping assay for the 2 SNPs. After DNA isolation and purification, real time PCR was performed to detect the SNPs of each gene.
 Results of this study showed the prevalence of one allele variant (heterozygous mutation) of UGT1A1*93 was 64% compared to 36% of patients were wild type to this SNP. No patient (0%) could be detected with homozygous polymorphism of the UGT1A1*93. For the ABCC5 polymorphism, results revealed that 32% of patients have one polymorphic allele (heterozygous), while 28% of them have two polymorphic alleles (homozygous mutation). Wild type ABCC5 gene constitutes 40% of patients. As a conclusion, high prevalence of UGT1A1*93 and ABCC5 polymorphic alleles were detected in patients at Middle Euphrates Cancer Center which may explain the high toxicity features associated with irinotecan therapy.

Quantitative assessment of the clinical susceptibility of calcium-sensing receptor polymorphisms in cancer patients.

BackgroundAccumulating evidence has suggested a relationship between calcium-sensing receptor (CASR) polymorphisms and cancer risk in different types of cancer; however, the findings from epidemiologic studies have been conflicting. The purpose of this meta-analysis was to assess the clinical susceptibility of CASR polymorphisms in cancer patients.Materials and methodsThis study systematically searched MEDLINE and EMBASE databases for eligible articles through March 2017. The strength of association was expressed as odds ratio and 95% CI. Publication bias, heterogeneity, sensitivity analysis, and subgroup analyses were also examined.ResultsFourteen related case–control studies were finally identified to be included in the present analysis. The pooled result showed that no significant associations were found among CASR rs1801725, rs1042636, rs12485716, rs4678174, rs1801726, rs17251221, rs10934578, and rs2270916 polymorphisms and cancer risk under all genetic models (P>0.05). The relationship between CASR rs1801725 polymorphism and risk of cancer was consistent in the subgroup analyses, and robust in sensitivity analysis. No publication bias was presented in our pooled-analysis.ConclusionThe current evidence for our pooled analysis suggests that the CASR polymorphisms are not associated with an increased risk of cancer. Further larger studies are still necessary to warrant and validate the findings in the current meta-analysis.

Identification of polymorphisms in cancer patients that differentially affect survival with age.

The World Health Organization predicts that the proportion of the world's population over 60 will almost double from 12% to 22% between 2015 and 2050. Ageing is the biggest risk factor for cancer, which is a leading cause of deaths worldwide. Unfortunately, research describing how genetic variants affect cancer progression commonly neglects to account for the ageing process. Herein is the first systematic analysis that combines a large longitudinal data set with a targeted candidate gene approach to examine the effect of genetic variation on survival as a function of age in cancer patients. Survival was significantly decreased in individuals with heterozygote or rare homozygote (i.e. variant) genotypes compared to those with a common homozygote genotype (i.e. wild type) for two single nucleotide polymorphisms (rs11574358 and rs4147918), one gene (SIRT3) and one pathway (FoxO signalling) in an age-dependent manner. All identified genes and pathways have previously been associated with ageing and cancer. These observations demonstrate that there are ageing-related genetic elements that differentially affect mortality in cancer patients in an age-dependent manner. Understanding the genetic determinants affecting prognosis differently with age will be invaluable to develop age-specific prognostic biomarkers and personalized therapies that may improve clinical outcomes for older individuals.

Relationship between UGT1A1*6/*28 gene polymorphisms and the efficacy and toxicity of irinotecan-based chemotherapy.

PurposeA retrospective study was performed to analyze the relationship between uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) *6/*28 gene polymorphisms and adverse reactions associated with irinotecan (CPT-11)-based chemotherapy. The correlation between UGT1A1 polymorphisms and the clinical efficacy of CPT-11 was also analyzed, along with the influence of age and tumor type.Patients and methodsPatients administered a CPT-11-based regimen in the Beijing Cancer Hospital from April 2015 to September 2016 were included in our study (n=81). Blood samples for detecting UGT1A1 were collected from each patient after various administration regimens.ResultsColorectal cancer patients with the UGT1A1*6 mutant genotype had a significantly higher risk of severe delayed diarrhea than that of wild-type individuals when administered a CPT-11 dose ≥130 mg/m2 (P=0.042); the same phenomenon was observed when the UGT1A1*6 and UGT1A1*28 mutant genotypes were considered together (P=0.028). However, in lung cancer patients administered a low dose of CPT-11, UGT1A1*6/*28 variants were not significantly associated with severe neutropenia or delayed diarrhea. Furthermore, adult patients with the UGT1A1*6 mutation were more likely to develop severe delayed diarrhea than did wild-type adults (P=0.013); however, the difference was not significant in elderly patients. No significant differences in tumor response were found among the different genotypes (P>0.05).ConclusionThus, age and tumor type influence our ability to predict adverse reactions based on UGT1A1 gene polymorphisms in cancer patients. Further, UGT1A1 gene polymorphisms are not correlated with the efficacy of CPT-11-based regimens.

Low Incidence of the DPD IVS14+1G>A Polymorphism in Jordanian Breast and Colorectal Cancer patients

Background:Dihydropyrimidine dehydrogenase (DPD) is a crucial enzyme in the catabolism of 5-fluorouracil (5-FU), a drug that is frequently used in cancer therapy. Patients with deficient DPD activity are at risk of developing severe 5-FU–associated toxicity. One possible cause of deficiency is genetic polymorphisms in the DPD gene, such as IVS14+1G>A.Aim:The present study was conducted to screen for the IVS14+1G>A polymorphism in cancer patients receiving 5-FU and a control group.Methods:A total of 40 cancer patients (30 colorectal cancer (CRC) and 10 breast cancer patients) were enrolled in this study. One hundred healthy controls were also tested using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). DNA sequence analysis was carried out to confirm the presence of the IVSI14+1G>A polymorphism.Results:Only one CRC patient showed heterozygous IVS14+1G>A polymorphism in the DPD gene.Conclusion:The results of this study demonstrated a very low frequency of the IVS14+1G>A polymorphism among Jordanian patients with colorectal and breast cancer.

Abstract IA32: Commensal microorganisms and polymorphic mucosal surfaces determine the evolution of distal metastatic tumors

Abstract Humans are symbiotic organisms in which bacteria outnumber eukaryotic cells in a ratio of 10 to 1. Interactions between commensal microorganisms and immune cells at mucosal surfaces forge the orchestration of a robust immune system that is able to defend us from infections. Critical for these interactions are pattern recognition receptors, including TLRs, which exhibit functional polymorphisms in at least 30% of individuals in the general population. We show that TLR5 recognition of commensal bacteria drives malignant progression at distant, extra-mucosal locations by promoting systemic up-regulation of IL-6, which is further increased through an autocrine loop in reactive tumor cells and drives MDSC mobilization. MDSCs expanded in response to systemic IL-6 elevation produce adenosine to transform T cells into immunosuppressive players that secrete higher levels of galectin-1 on a per cell basis than any other cell type in the tumor microenvironment. In contrast, in TLR5-unresponsive individuals, there is systemic up-regulation of IL-17 during tumor development. However, this is only relevant for tumor growth when tumors generate relatively low levels of circulating IL-6, resulting in accelerated malignant progression in the absence of TLR5 signaling. Importantly, depletion of commensal bacteria abrogates any variations in tumor progression and has opposite effects in tumors that grow faster in TLR5-competent individuals (delaying malignant progression) vs. tumors that progress faster in the absence of TLR5 signaling (where malignant progression is accelerated). Shockingly, depletion of commensal bacteria has opposite effects in the progression of primary vs. metastatic breast tumors, thus opening new avenues to understand breast cancer recurrence and tumor dormancy. Together, our data indicate that both tumor-promoting inflammation and anti-tumor immunity are influenced by TLR5 signaling, which depends on a common genetic polymorphism in cancer patients. Citation Format: Melanie R. Rutkowski, Jose R. Conejo-Garcia. Commensal microorganisms and polymorphic mucosal surfaces determine the evolution of distal metastatic tumors. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr IA32.

Significance of Polymorphisms and Expression of Enzyme-Encoding Genes Related to Glutathione in Hematopoietic Cancers and Solid Tumors.

Antioxidant compounds such as glutathione and its enzymes have become the focus of attention of medical sciences. Glutathione, a specific tripeptide, is involved in many intercellular processes. The glutathione concentration is determined by the number of GAG repeats in gamma-glutamylcysteine synthetase. GAG polymorphisms are associated with an increased risk of schizophrenia, berylliosis, diabetes, lung cancer, and nasopharyngeal tumors. Cancer cells with high glutathione concentration are resistant to chemotherapy treatment. The oxidized form of glutathione is formed by glutathione peroxidases (GPXs). The changes in activity of GPX1, GPX2, and GPX3 isoforms may be associated with the development of cancers, for example, prostate cancer or even colon cancer. Detoxification of glutathione conjugates is possible due to activity of glutathione S-transferases (GSTs). Polymorphisms in GSTM1, GSTP1, and GSTO1 enzymes increase the risk of developing breast cancer and hepatocellular carcinoma. Gamma-glutamyl transpeptidases (GGTs) are responsible for glutathione degradation. Increased activity of GGT correlates with adverse prognosis in patients with breast cancer. Studies on genes encoding glutathione enzymes are continued in order to determine the correlation between DNA polymorphisms in cancer patients.

Interindividual Variations in Aprepitant Plasma Pharmacokinetics in Cancer Patients Receiving Cisplatin-Based Chemotherapy for the First Time

The pharmacokinetics of aprepitant, a neurokinin-1 receptor antagonist, have not been fully evaluated in clinical settings. The aim of this study was to characterize the plasma pharmacokinetics of aprepitant and reveal their influence of laboratory tests and cytochrome P450 (CYP) 3A5 gene polymorphisms in cancer patients. Forty-four Japanese cancer patients receiving cisplatin-based chemotherapy for the first time following oral aprepitant (125 mg on day 1 and 80 mg on days 2 and 3) were enrolled. The patients did not have gastrointestinal disease and the clinical laboratory values were within their normal reference levels. The plasma concentrations of aprepitant 24 (day 2 predose), 72, and 120 h after the first aprepitant administration were determined using LC-MS/MS. The relationships between plasma exposure to aprepitant and body weight, clinical laboratory values, age, gender, or CYP3A5*3 were investigated. The median and interquartile ranges of the 120-h area under the plasma concentration time curve (AUC)(0-120) of aprepitant were 73215 and 55518-91121 ng h/mL. The coefficient of variation value for aprepitant AUC(0-120) was 53%. The AUC(0-120) of aprepitant was correlated with the levels of total bilirubin and serum albumin, respectively (r=0.454, p<0.01 and r=0.287, p=0.06), but not with other non-genetic factors and CYP3A5 genetic variants in a univariate analysis. The AUC(0-120) of aprepitant was significantly correlated with the level of total bilirubin (adjusted R(2)=0.187, p<0.01) in a multivariate analysis. In conclusion, the plasma pharmacokinetics of aprepitant varied markedly in cancer patients receiving cisplatin-based chemotherapy for the first time and were correlated with the level of total bilirubin.

Abstract CN04-01: Contribution of polymorphic transporters to oncology drug disposition and safety.

Abstract CN04-01: Contribution of polymorphic transporters to oncology drug disposition and safety.

Protease activated receptor 1 gene −506 I / D polymorphism in cancer patients with and without venous thrombosis

European Journal of HaematologyVolume 86, Issue 6 p. 546-547 LETTER TO THE EDITOR Protease activated receptor 1 gene −506 I / D polymorphism in cancer patients with and without venous thrombosis Afife Karabıyık, Afife Karabıyık Department of Pediatric Genetic, Ankara University Medical School, AnkaraSearch for more papers by this authorAydan Eroğlu, Aydan Eroğlu Department of General Surgery, Surgical Oncology, Ankara University Medical School, AnkaraSearch for more papers by this authorNejat Akar, Nejat Akar Department of Pediatric Genetic, Ankara University Medical School, Ankara, TurkeySearch for more papers by this author Afife Karabıyık, Afife Karabıyık Department of Pediatric Genetic, Ankara University Medical School, AnkaraSearch for more papers by this authorAydan Eroğlu, Aydan Eroğlu Department of General Surgery, Surgical Oncology, Ankara University Medical School, AnkaraSearch for more papers by this authorNejat Akar, Nejat Akar Department of Pediatric Genetic, Ankara University Medical School, Ankara, TurkeySearch for more papers by this author First published: 05 March 2011 https://doi.org/10.1111/j.1600-0609.2011.01600.xCitations: 1 Aydan Eroğlu, MD, Department of General Surgery, Surgical Oncology, Ankara University Medical School, Cebeci Kampus, 06590 Ankara, Turkey. Tel: +903125957248; Fax: +90312 3191191; e-mail: [email protected] Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume86, Issue6June 2011Pages 546-547 RelatedInformation

Molecular oncology focus - Is carcinogenesis a 'mitochondriopathy'?

Mitochondria are sub-cellular organelles that produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). As suggested over 70 years ago by Otto Warburg and recently confirmed with molecular techniques, alterations in respiratory activity and in mitochondrial DNA (mtDNA) appear to be common features of malignant cells. Somatic mtDNA mutations have been reported in many types of cancer cells, and some reports document the prevalence of inherited mitochondrial DNA polymorphisms in cancer patients. Nevertheless, a careful reanalysis of methodological criteria and methodology applied in those reports has shown that numerous papers can't be used as relevant sources of data for systematic review, meta-analysis, or finally for establishment of clinically applicable markers.In this review technical and conceptual errors commonly occurring in the literature are summarized. In the first place we discuss, why many of the published papers cannot be used as a valid and clinically useful sources of evidence in the biomedical and healthcare contexts. The reasons for introduction of noise in data and in consequence - bias for the interpretation of the role of mitochondrial DNA in the complex process of tumorigenesis are listed. In the second part of the text practical aspects of mtDNA research and requirements necessary to fulfill in order to use mtDNA analysis in clinics are shown. Stringent methodological criteria of a case-controlled experiment in molecular medicine are indicated. In the third part we suggest, what lessons can be learned for the future and propose guidelines for mtDNA analysis in oncology. Finally we conclude that, although several conceptual and methodological difficulties hinder the research on mitochondrial patho-physiology in cancer cells, this area of molecular medicine should be considered of high importance for future clinical practice.

Mitochondrial NADH-dehydrogenase subunit 3 (ND3) polymorphism (A10398G) and sporadic breast cancer in Poland

Mitochondria are subcellular organelles that produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). As suggested over 70 years ago by Otto Warburg and recently confirmed with molecular techniques, alterations in respiratory activity and mitochondrial DNA (mtDNA) appear to be common features of malignant cells. Somatic mtDNA mutations have been reported in many types of cancer cells, but very few reports document the prevalence of inherited mitochondrial DNA polymorphisms in cancer patients compared to healthy control populations. Here we report the abundance of the 10398G polymorphism in a Polish breast cancer population and its frequency in controls. Amongst individuals with breast cancer the G single nucleotide polymorphism (SNP) is present in 23% of affected females compared to 3% of controls. This difference is highly statistically significant (P = 0.0008). It is therefore possible that the 10398G SNP constitutes an inherited predisposition factor for the development of breast cancer.

The 19-bp deletion of dihydrofolate reductase (DHFR), methylenetetrahydrofolate reductase (MTHFR) C677T, Factor V Leiden, prothrombin G20210A polymorphisms in cancer patients with and without thrombosis

Venous thromboembolism (VTE) is a common complication in cancer patients. Several genetic risk factors related to thrombophilia are known; however, their contributions to thrombotic tendency in cancer patients have conflicting results. In the present study, we have focused on the prevalence of methylenetetrahydrofolate reductase (MTHFR) C677T, dihydrofolate reductase (DHFR) 19-bp deletion within intron 1, factor V Leiden (FVL), and prothrombin (PT) G20210A polymorphisms in cancer patients with and without VTE. The study consisted of 63 cancer patients with VTE (group 1) and 124 cancer patients who had no evidence of VTE (group 2). Four gene polymorphisms were determined by the method of polymerase-chain-reaction-based DNA analysis. The prevalence of DHFR 19-bp deletion and MTHFR C677T polymorphisms was similar in two groups (p > 0.05). The frequency of FVL was significantly higher in group1 compared with group 2 (31.7% vs. 1.6%, p < 0.0001), but PT G20210A polymorphism was not associated with VTE. Cancer patients with thrombosis should be evaluated for FVL, but routine screening for PT G20210A, MTHFR C677T and DHFR 19-bp deletion polymorphisms is not suggested.

Identification and expression analysis of novel LAGE-1 alleles with single nucleotide polymorphisms in cancer patients

The purpose of this study is to identify single nucleotide polymorphisms (SNPs) in the coding region alleles of the X chromosomal LAGE-1 gene, and investigate the frequency of such SNPs in both cancer patients and healthy controls, and thus determine the potential significance of these SNPs with respect to cancer vaccine therapy. In this study, different mRNAs transcribed from the LAGE-1 gene were identified by RT-PCR from healthy donors and cancer patients samples. A new LAGE-1 allele containing three coding region SNPs (69A/G, 317C/G, and 397T/G) were identified. The allele is highly expressed as the LAGE-1a mRNA variant AY679089 in some of the cancer patients. The three SNPs altered the LAGE-1 gene sequence to that of NYESO-1 at both the nucleotide and amino acid level. There is a high frequency of the LAGE-1 gene allele with SNPs in coding regions in cancer patients. There was a clear relationship between the variant AY679089 and gastric cancer. The SNPs may lead to accelerated progress of poorly differentiated gastric cancer. The SNPs found in these alleles may also alter the immunological characteristics of LAGE-1a and should be taken into account if this antigen is adopted as a cancer vaccine component.

Role of Tumor Necrosis Factor Gene Polymorphism (-308 and -238) in Colorectal Cancer Susceptibility

Purpose: The purpose of this study is to investigate the potential association of tumor necrosis factor-α (TNF-α) promoter polymorphisms (-308 G>A and -238 G>A) with colorectal cancer susceptibility. Methods: The study included 77 patients with colorectal cancer and 100 healthy controls. The polymorphisms were genotyped for these TNF-α polymorphisms by PCR-Pyrosequencing (Fig. 1). The distributions of TNF-α promoter polymorphisms were compared between cancer patients and healthy controls by the chi-square test. Odds ratios (OR) and 95% confidence intervals (CI) were also calculated. Results: The Genotype distributions and allele frequencies of the -308 (rs361525) and -238 (rs1800629) TNF-α polymorphism in cancer patients and controls are shown in Table 1. Although the TNF-308A allele frequency was lower in the cancer group compared with the control group (7.8% vs. 14.5%) and TNF-238A allele frequency was higher (7.8% in cancer group vs. 6% in controls), the observed differences were not statistically significant (P > 0.05). The odds ratio for cancer in subjects with the TNF-308A allele was 0.55(95% CI, 0.24–1.25) and with the TNF-238A allele was 1.05 (95% CI, 0.37–3.0).Table 1: Distributions of the two tumor necrosis factor (TNF) polymorphisms in colorectal cancer patients and healthy controlsConclusion: We found no association between the -308G>A polymorphism and the -238G>A polymorphism in the promoter region of TNF-α and susceptibility to colorectal cancer in an Iranian population.[figure1]

Mutations and polymorphisms of the p21B transcript in breast cancer

p21(WAF1/CIP1), transcribed from the CDKN1A locus, plays a key role executing p53-induced growth arrest. The recent discovery that an alternative transcript, p21B, induces apoptosis, suggests an additional important function of this gene. Here, we report p21 and p21B mutation status in large cohorts of breast cancers and compare distributions of p21B polymorphisms in cancer patients to healthy controls. In 521 breast tumor samples analyzed, only one point mutation affecting the p21B protein was observed. No mutations were found when screening a panel of 20 established cell lines. A novel polymorphism, p21B(G128T) was identified. Haplotype analysis revealed no association between this variant and the previously identified p21B polymorphism p21B(T35C) or any of the known p21(WAF1/CIP1) polymorphisms. As previously reported for p21B(T35C), distribution of p21B(G128T) was similar among breast cancer patients and healthy controls (n = 691 and 1,015; incidence 6.1 vs. 4.8%; p = 0.273, respectively). No association between p21B(G128T) or p21B(T35C) and response to chemotherapy with an anthracycline-containing regimen or paclitaxel was recorded. Our findings do not suggest mutations or polymorphisms of p21B to play a major role with respect to either breast cancer risk or sensitivity towards chemotherapy.

Prevalence of Factor V 1691 G–A (Leiden) and prothrombin G20210A polymorphisms and the risk of venous thrombosis among cancer patients

Cancer patients have an increased risk for thromboembolism (TE). Factor V 1691 G-A(Leiden) (FVL) and prothrombin (PT) G20210A mutation are common inherited risk factor for TE. The aim of the study is to evaluate the prevalence of FVL and PT G20210A polymorphism in cancer patients with and without TE as compared to patients with TE without malignancy and healthy control. We have studied 43 cancer patients who developed TE during cancer treatment (group 1); 81 cancer patients without TE (group 2); 100 patients with TE without malignancy (group 3); 100 healthy control (group 4). FVL and PT G20210A polymorphisms were determined by the method of polymerase chain reaction-based DNA analysis. The prevalence of FVL was significantly greater in cancer patients with TE (13 of 43, 30.2%) compared with other groups: 3.7% in group 2; 18% in group 3; 8% in group 4 (P < 0.0001). There was no significant difference in the prevalence of PT G20210A among the groups (P > 0.05). The study suggested that cancer patients with TE should be evaluated for FVL but PT G20210A was not contributing factor to the development of TE during cancer therapy.

Plasminogen activator inhibitor-1 gene 4G/5G polymorphism in cancer patients with and without thrombosis

Plasminogen activator inhibitor-1 gene 4G/5G polymorphism in cancer patients with and without thrombosis