UGT1As polymorphisms predict toxicity in colorectal cancer patients treated with different recommended doses of irinotecan oriented by UGT1A1*28 polymorphism based on previous phase I study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14511-14511 ◽  
Author(s):  
S. Hazama ◽  
H. Koudo ◽  
S. Yoshida ◽  
R. Shimizu ◽  
H. Ozasa ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Maximum Tolerated Dose ◽  
Wild Type ◽  
Eligibility Criteria ◽  
Metastatic Lesions ◽  
Significant Difference ◽  
The Difference ◽  
Colorectal Cancer Patients ◽  
Previous Phase ◽  
Written Informed Consent

14511 Background: We have presented at 2006 ASCO annual meeting about a genetic UGT1A1 polymorphism oriented phase (P) I study of Irinotecan and 5’-DFUR for metastatic colorectal cancer (MCRC) to determine the maximum tolerated dose (MTD) and the recommend doses (RD) for each UGT1A1 *1/*1 and *1/*28 genotypes. The RD of biweekly Irinotecan administration was 150 mg/m2 for patients (pts) with wild *1/*1 genotype and 70 mg/m2 of Irinotecan for mutated *1/*28. Now we are carrying out a *28 oriented P II study based on this RD. Here we report the profiles of toxicities in the P II study of irinotecan and 5’-DFUR to analyze other kinds of UGT1As polymorphisms in relation to irinotecan toxicities. Patients & Methods: Eligibility criteria were as follows; histologically proven CRC with unresectable metastatic lesions, PS 0–1, age<76, adequate organ functions, and written informed consent. Twenty one pts with wild type genotype and 9 pts with mutated genotype were enrolled. Irinotecan was infused 150 mg/m2 for pts with *1/*1 genotype and 70 mg/m2 for *1/*28. Hematological and non-hematological toxicities were graded, and UGT1As polymorphisms (UGT1A1*6 and *7, UGT1A7*1*2*3*4, UGT1A9*22) were analyzed. Results: Grade (G)3 & 4 toxicities were observed in 6 of 22 (27%) wild type pts and in 3 of 9 (33%) mutated pts, and in 9 of 31 (29%) all pts. There was no significant difference on the profiles of toxicities between the pts with wild genotype and mutated genotype, irrespective of the difference of the quantity of irinotecan. So, the RD was thought to be adequate. In pts with UGT1A1*6 allele, G3 & 4 toxicities were observed 6/11 (55%), on the other hand 3/20 (15%) in pts without *6 allele (p=0.038). G3 & 4 toxicities were also more frequent in pts with UGT1A7*3 alleles than pts without *3 allele (p<0.10). Conclusions: The profiles of toxicities of pts with *1/*1 or *1/*28 genotypes were similar irrespective of the difference of the quantity of irinotecan. The result indicated that the RD of latest PI for each group was adequate, and this P II study is suitable to analyze other kinds of polymorphisms that have correlation to irinotecan toxicities. UGT1A1*6 and UGT1A7*3 allele will be a novel predictor for toxicity of irinotecan. No significant financial relationships to disclose.

KRAS mutation profile in colorectal cancer patients in Brazil: A cohort of 989 individuals

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15017-e15017
Author(s):  
M. G. Zalis ◽  
F. M. Vieira ◽  
I. Zalcberg-Renault ◽  
M. H. Bonamino ◽  
C. G. Ferreira ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Kras Mutation ◽  
Genetic Background ◽  
Brazilian Population ◽  
Wild Type ◽  
Asian Populations ◽  
Mutation Profile ◽  
Significant Difference ◽  
Colorectal Cancer Patients

e15017 Background: KRAS mutation is common event in colorectal cancer occurring in around 40% of the patients. It is well- known that patients harboring the KRAS mutation do not derive benefit from cetuximab. However data available KRAS mutation profile is limited to Caucasian and Asian individuals and there is a lack of data in the population from Latin America. Brazilian population has a heterogeneous genetic background and this may have pharmacogenetic implications (Suarez-Kurtz, 2006). Methods: Between July and November 2008, we analyzed 989 consecutive patient samples sent to our laboratory for KRAS genotyping as a screening for cetuximab use. DNA was extracted from paraffin-embedded tissue, exons 1 were amplified by PCR and submitted to automatic sequencing. Codons 12 and 13 were analyzed. Results: The median age was 59 years and 53% of the patients were male and 47% female. The percentage of wild-type and mutated KRAS was 62 and 38%, respectively. Among the 375 mutated cases, 87% were in codon 12 versus 13% in codon 13. Mutation Gly12Asp was the most common being detected in 39% of the mutated cases. Due to the sample size a comparison among patients from different regions of Brazil was possible. However, no significant difference was observed in relation to the type or percentage of patients harboring the KRAS mutation. Interestingly, a significant difference in the percentage of mutated KRAS patients was observed between male and female (41 versus 35%, p= 0.05). Conclusions: The profile of KRAS mutation in the Brazilian population is similar to that reported for Caucasian and Asian populations. This is one of the largest cohorts of KRAS genotyping in colorectal cancer patients ever reported. To the best of our knowledge our data is the first to put forward the issue of a potential difference in the mutation rate according to gender. The observed higher incidence of KRAS-mutation in male than female deserves further investigation. No significant financial relationships to disclose.

Predictive value of ERCC1 and KRAS in colorectal cancer patients with FOLFOX chemotherapy.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 588-588
Author(s):  
In Kyu Lee ◽  
Sung-Bong Choi ◽  
DaeYoung Cheung ◽  
Jin Il Kim
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Kras Mutation ◽  
Disease Free Survival ◽  
Wild Type ◽  
Free Survival ◽  
Significant Difference ◽  
Colorectal Cancer Patients ◽  
Disease Free

588 Background: To determine the clinical significance of KRAS mutation and ERCC1 overexpression as a predictive factor of resistance in oxaliplatin based treatment. Methods: We retrospectively analyzed the clinicopathologic features, status of KRAS mutation and ERCC1 overexpression of 386 colorectal cancer patients who received curative intent surgery. Among them 84 patients were treated by FOLFOX regimen as the first line. Their disease-free survival and overall survival according to the KRAS and ERCC1 were analyzed. Results: About a quarter of patients (25.5%) were represented KRAS wild type with ERCC1 overexpression. Among the patients who treated by FOLFOX regimen, 73 patients were evaluated both of the KRAS and ERCC1. There were no significant differences of disease-free survival and overall survival according to KRAS status and ERCC1 expression each. Under the subgroup analysis, overall survival of ERCC1 overexpression group in wild type KRAS was poor than ERCC1 negative group (p=.029), but no significant difference was in mutant KRAS group (p=.671). Conclusions: Our results suggest that the KRAS wild type with ERCC1 overexpression would be associated with the resistance of oxaliplatin.If oxaliplatin based chemotherapy would beconsidered, status of KRAS mutation and ERCC1 overexpression should be evaluated.

scholarly journals Derajat Toksisitas Hemoglobin Pada Penderita Kanker Kolorektal Yang Mendapat Kemoterapi CapeOX

2020 ◽  
Vol 1 (4) ◽  
pp. 299-305
Author(s):  
Yusmaidi ◽  
Jordy Oktobiannobel ◽  
Muhammad Nur ◽  
Bella Sabila Dananda
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
The United States ◽  
Hematological Toxicity ◽  
P Value ◽  
Chemotherapy Drugs ◽  
Number Of Patients ◽  
Significant Difference ◽  
The Difference ◽  
Colorectal Cancer Patients

Advances in the treatment and use of chemotherapy have been shown to improve the life expectancy rate for colorectal cancer patients. Studies conducted in China and Hongkong have shown that CapeOX combination chemotherapy regimens are more commonly used than in Europe and the United States. However, the use of chemotherapy drugs containing oxaliplatin and capecitabine can cause side effects such as hematological toxicity, which is one of them is anemia. This study aims to determine the difference in the form of a decrease in the average levels of hemoglobin and the degree of hemoglobin toxicity in colorectal cancer patients undergoing CapeOX chemotherapy. The Design in this study is a historical (retrospective) cohort. This study sample was 70 colorectal cancer patients who received CapeOX chemotherapy for 6 cycles at RSUD Dr. H. Abdul Moeloek in 2018-2019. Consecutive sampling is used in the sampling method. The statistical analysis is using Paired T-Test. There is a significant difference in the average hemoglobin level of colorectal cancer patients (p-value = <0.005), which receive CapeOX chemotherapy for 6 cycles.  Besides, there is an increase in the number of patients who get hemoglobin toxicity and the chemotherapy cycle. In the first cycle, 59 patients (84.3%) got hemoglobin toxicity after chemotherapy, and the number continued to increase to 69 patients (98.6%) in the sixth cycle. There was a decrease in hemoglobin levels in colorectal cancer patients who received CapeOX chemotherapy with p-value = <0.05 and increased patients who got hemoglobin toxicity.

Combined mutational analysis of KRAS, NRAS and BRAF genes in Indian patients with colorectal carcinoma

2012 ◽  
Vol 27 (1) ◽  
pp. 27-33 ◽  
Author(s):  
Sarita B. Bagadi ◽  
Meera Sanghvi ◽  
Sudish B. Nair ◽  
Bibhu R. Das
Keyword(s):  
Colorectal Cancer ◽  
Colorectal Carcinoma ◽  
Mutational Analysis ◽  
Growth Factor Receptor ◽  
Tumor Location ◽  
Wild Type ◽  
Significant Difference ◽  
Unknown Significance ◽  
Exon 1 ◽  
Colorectal Cancer Patients

The epidermal growth factor receptor (EGFR) is an excellent candidate for targeted therapy in colorectal cancer. Recent studies have demonstrated that apart from wild-type KRAS, a wild-type BRAF and NRAS genotype is required for response to anti-EGFR therapy. This suggests that NRAS and BRAF genotype criteria should be used together with KRAS genotype to select patients who will likely benefit from anti-EGFR therapy. We investigated the prevalence of mutations in the KRAS, BRAF and NRAS genes and its correlation with demographic characteristics, tumor location and stage in 100 colorectal carcinoma patients from India. The frequency of KRAS, BRAF and NRAS mutations was found to be 23%, 17% and 2.0%, respectively. There was no significant difference in KRAS, NRAS and BRAF mutation with respect to gender, age, tumor location (colon vs rectum) and clinicopathological stage. In addition, we found a novel point variant (T20I) of unknown significance in NRAS exon 1 in addition to a KRAS codon 12 mutation in one of the rectal carcinoma patients. In the present study, combined evaluation of genetic biomarkers (KRAS, NRAS and BRAF) was able to classify 42% of colorectal cancer patients as likely non-responders to anti-EGFR therapy.

scholarly journals Significant Associations of lncRNA H19 Genotypes with Susceptibility to Childhood Leukemia in Taiwan

2021 ◽  
Vol 14 (3) ◽  
pp. 235
Author(s):  
Jen-Sheng Pei ◽  
Chao-Chun Chen ◽  
Wen-Shin Chang ◽  
Yun-Chi Wang ◽  
Jaw-Chyun Chen ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Childhood Leukemia ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Wild Type ◽  
Single Nucleotide ◽  
Genotypic Distribution ◽  
Heterozygous Variant ◽  
Significant Difference ◽  
The Difference

The purpose of our study was to investigate whether genetic variations in lncRNA H19 were associated with susceptibility to childhood leukemia. Two hundred and sixty-six childhood leukemia patients and 266 healthy controls were enrolled in Taiwan, and two single nucleotide polymorphisms (SNPs), rs2839698 and rs217727, in H19 were genotyped and analyzed. There was a significant difference in the genotypic distribution of rs2839698 between patients and healthy controls (p = 0.0277). Compared to the wild-type CC genotype, the heterozygous variant CT and homozygous variant TT genotypes were associated with significantly increased risks of childhood leukemia with an adjusted odd ratio (OR) of 1.46 (95% confidence interval (CI), 1.08–2.14, p = 0.0429) and 1.94 (95%CI, 1.15–3.31, p = 0.0169), respectively (pfor tread = 0.0277). The difference in allelic frequencies between childhood leukemia patients and controls was also significant (T versus C, adjusted OR = 1.53, 95%CI, 1.13–1.79, p = 0.0077). There were no significant differences in the genotypic and allelic distributions of rs217727 between cases and controls. Interestingly, the average level of H19 rs2839698 was statistically significantly higher for patients with CT and TT genotypes than from those with the CC genotype (p < 0.0001). Our results indicate that H19 SNP rs2839698, but not rs217727, may serve as a novel susceptibility marker for childhood leukemia.

scholarly journals EZH2 Expression and its Correlation with Clinicopathological Features in Patients with Colorectal Carcinoma

2016 ◽  
Vol 11 (1) ◽  
pp. 287-292
Author(s):  
Xiao-yang Liu ◽  
Hua Liu ◽  
Lin Gu ◽  
Hai-lun Zheng
Keyword(s):  
Colorectal Cancer ◽  
Colorectal Carcinoma ◽  
Disease Progression ◽  
Western Blotting ◽  
Progression Free Survival ◽  
Clinicopathological Features ◽  
Tumor Biomarker ◽  
Ezh2 Expression ◽  
Significant Difference ◽  
Colorectal Cancer Patients

AbstractObjectiveTo explore the correlation between the enhancer of zeste homolog 2 (EZH2) expression and clinicopathological features in colorectal cancer patients.MethodsA total of sixty-six patients with colorectal carcinoma were admitted to our general surgery department from January 2011 to December 2014. The EZH2 expression levels in the cancer tissues (CTs) from the 66 patients with colorectal cancer and those in distant normal colorectal tissues from 30 cases were examined through immunohistochemistry and western blotting assays. The relationship between the expression of EZH2 and the clinicopathological features and prognosis of the patients was analyzed.ResultsEZH2 in colorectal carcinoma tissues is granularly brown, predominantly expressed and diffused in the nuclei of tumor cells. Positive rates of EZH2 in intestinal CTs and in distant normal intestinal tissues are 62.12% (41/66) and 6.67% (2/30), respectively with significant difference (P < 0.05). Western blotting also confirmed its elevated expression in colorectal CTs. EZH2-positive expression in CTs was related to degree of differentiation, Duke staging, and tumor size (P < 0.05) but was unrelated to the patient’s gender, age or tumor site (P = 0.05). The 3-year progression-free survival (PFS) rates of the EZH2-positive group and the EZH2-negative group were 43.8% and 67.5%, respectively. The risk of disease progression of the EZH2-positive patients in the follow-up period was significantly higher than that of the EZH2-negative patients (HR = 2.49, 95% CI = 1.04–4.80, P < 0.05).ConclusionEZH2 is closely related to colorectal carcinoma development and disease progression, and thus could be used as a tumor biomarker that may indicate prognosis.

scholarly journals Perbedaan Penyembuhan Luka Pasca Ekstraksi Gigi Antara Pasien Perokok Dengan Bukan Perokok Di RSGM Unsrat

e-GIGI ◽  
2019 ◽  
Vol 7 (2) ◽  
Author(s):  
Lidia A. Kewo ◽  
Damajanty H.C. Pangemanan ◽  
Aurelia Supit
Keyword(s):  
Wound Healing ◽  
Tooth Extraction ◽  
Soft Tissues ◽  
P Value ◽  
Eligibility Criteria ◽  
Cross Sectional ◽  
Inflammatory Phase ◽  
Significant Difference ◽  
The Difference ◽  
Cross Sectional Design

Abstract: To date, there are lots of documentations about the adverse effects of smoking on the oral cavity. Albeit, smoking is still considered as a casual thing in our community. Chemicals contained in the cigarette smoke can irritate the gums and soft tissues of the mouth, thus inhibiting wound healing after tooth extraction. This study was aimed to determine the difference in post-extraction dental wound healing between smokers and non-smokers. This was a comparative analytical study with a cross sectional design. Samples were obtained by using total sampling method. Subjects consisted of 16 smokers and 16 non-smokers that fulfilled the study eligibility criteria. Their oral cavities were examined to check the signs of inflammation (calor, dolor, rubor, tumor, and functio laesa). The results showed that there was a difference in post-extraction wound healing in inflammatory phase between smokers and non-smokers. As many as 9.4% of smoker patients and 34.4% of non-smoker patients recovered at 7 days post extraction. The Mann Whitney U test showed a p-value of 0.005. In conclusion, there was a significant difference in post-extraction wound healing between smokers and non-smokers.Keywords: smokers, non-smokers tooth extraction, wound healing Abstrak: Kebiasaan merokok bukan merupakan hal asing di masyarakat walaupun banyak dokumentasi mengenai akibat buruk dari merokok terhadap rongga mulut. Bahan kimia yang terdapat dalam asap rokok dapat mengiritasi gusi dan jaringan lunak mulut sehingga menghambat penyembuhan luka pasca ekstraksi gigi. Penelitian ini bertujuan untuk mengetahui perbedaan penyembuhan luka pasca ekstraksi gigi antara pasien perokok dengan bukan perokok. Jenis penelitian ialah analitik komparatif dengan desain potong lintang. Pengambilan sampel menggunakan total sampling yang memenuhi kriteria penelitian. Terdapat sebanyak 16 orang perokok dan 16 orang bukan perokok sebagai subyek penelitian. Pemeriksaan rongga mulut dilakukan untuk melihat tanda-tanda inflamasi (kalor, dolor, rubor, tumor, dan fungsio laesa). Hasil penelitian menunjukkan terdapat perbedaan penyembuhan luka 7 hari pasca ekstraksi gigi pada fase inflamasi antara pasien perokok dengan yang bukan perokok; sebanyak 9,4% pasien perokok dan 34,4% pasien bukan perokok yang sudah sembuh. Hasil uji Mann Whitney U mendapatkan nilai p=0,005. Simpulan penelitian ini ialah terdapat perbedaan bermakna dalam penyembuhan luka pasca ekstraksi gigi antara pasien perokok dengan yang bukan perokokKata kunci: perokok, bukan perokok, ekstraksi gigi, penyembuhan luka

scholarly journals POTENTIAL PREVENTIVE EFFECT OF LACTOBACILLUS ACIDOPHILUS AND LACTOBACILLUS PLANTARUM IN PATIENTS WITH POLYPS OR COLORECTAL CÂNCER

2018 ◽  
Vol 55 (4) ◽  
pp. 407-411 ◽  
Author(s):  
Nazi ZINATIZADEH ◽  
Farzad KHALILI ◽  
Parviz FALLAH ◽  
Malihe FARID ◽  
Maryam GERAVAND ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lactobacillus Plantarum ◽  
Lactobacillus Acidophilus ◽  
Rrna Gene ◽  
Preventive Effect ◽  
Healthy Group ◽  
Significant Difference ◽  
Average Copy ◽  
And Gender ◽  
Colorectal Cancer Patients

ABSTRACT BACKGROUND: Colorectal cancer is one of the major causes of death worldwide. Many studies have been done on the biology of its formation as well as its treatment in recent years. One of the factors involved in the formation or treatment of this malignancy can be attributed to the microbial flora in the intestine. OBJECTIVE: This study investigate the potential preventive effect of Lactobacillus acidophilus and Lactobacillus plantarum in patients with polyps or colorectal cancer (CRC). METHODS: A total of 77 samples were selected in the form of three groups including individuals suffering from CRC, polyps and healthy subjects. Genomic DNA of fecal specimens and standard strains were extracted and amplified employing primers targeting of the 16S rRNA gene for initial detection. Absolute Real Time PCR quantification was used to determine the copy of the bacterial expression per gram of feces. RESULTS: No significant difference were observed between age and gender in the mentioned groups (P=0.06). The average copy number of Lactobacillus acidophilus shows Significant difference between the healthy group and those with polyps (P<0.0001), the healthy group and those with colorectal cancer (P<0.0001), as well as those with polyps and the colorectal cancer patients (P<0.0001). CONCLUSION: These results may indicate that taking Lactobacillus acidophilus in people with a family history of CRC and people with polyps may be a way of preventing, treating or reducing the severity of CRC.

Relationship between Genetic Polymorphism of CYP1A1 at Codon 462 (Ile462Val) in Colorectal Cancer

2008 ◽  
Vol 23 (1) ◽  
pp. 18-23 ◽  
Author(s):  
P.V. Pereira Serafim ◽  
I.D. Cotrim Guerreiro da Silva ◽  
N. Manoukian Forones
Keyword(s):  
Colorectal Cancer ◽  
Group Versus ◽  
Positive Association ◽  
Control Group ◽  
Case Group ◽  
Wild Type ◽  
Cancer Group ◽  
Increased Risk ◽  
Colorectal Cancer Patients ◽  
Alcohol Users

Aims and background The enzyme cytochrome P450 plays an important role in the metabolization and detoxification of various compounds. CYP1A1 is a polymorphic enzyme and some of its alleles have been correlated with an increased risk of developing various types of cancer. The aim of this study was to investigate the incidence of the polymorphism A→G (Ile462Val, exon 7) in colorectal cancer patients and the correlation of this polymorphism with others risk factors. Patients and methods 114 Brazilian patients with colorectal cancer were matched by age and sex to 114 healthy individuals. DNA was extracted from peripheral blood and the genotypes of the polymorphisms were assessed by PCR-restriction fragment length polymorphism. Results In the case group 64 subjects were male, 53 were alcohol users and 68 were smokers. In the control group 61 were male, 67 were alcohol users and 53 smokers. There were 14 subjects with wild-type homozygous A/A, 97 with heterozygous A/G, and 3 with homozygous mutated G/G in the cancer group versus 81 subjects with wild-type homozygous A/A and 33 with heterozygous A/G in the control group. The presence of the G allele (OR 5.14, 95%CI 3.15–10.80) was associated with an increased risk of colorectal cancer (p=0.001). The prevalence of smokers was higher in the cancer group (p=0.047, OR 1.71, 95%CI 1.03–3.11). Conclusion These results suggest a positive association between the A→G polymorphism and the risk of colorectal cancer. In addition, smoking was also a colorectal cancer risk. We did not find any correlation between this polymorphism and sex, grade of differentiation, stage, or evolution of the disease.

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