Study of genetic detection of KRAS, FCGR, CYP3A5 and CYP1A1 in predicting clinical outcomes of chemotherapy/target therapy in metastatic colorectal cancer (mCRC) / 中国医师杂志

Objective To investigate the predictive and prognostic value of genetic detection of Kirsten rat sarcoma viral oncogene homolog(KRAS),Fc gamma receptors (FCGR),cytochrome P450 3A5 (CYP3A5) and CYP1A1 in patients with metastatic colorectal cancer (mCRC) receiving C225 combined with CapeOx chemotherapy.Methods Twelve KRAS wild-type (WT) mCRC patients were selected receiving C225 (cetuximab) combined with CapeOx (capecitabine/oxaliplatin) chemotherapy.KRAS,FCGR,CYP3A5,CYP1 A1 gene mutation were detected before treatment.The expressions of phosphatase and tensin homolog deleted on chromosome ten (PTEN) were detected in colorectal cancer tissues and the corresponding adjacent tissues expression with immunohistochemical staining (SP method).The relationship between FCGR,CYP3A5,CYP1A1 mutation,and PTEN expression and survival time were analyzed.Results The mutation rates of FCGR,CYP3A5,and CYP1 A1 were 16.7％ (2/12),25％ (3/12) and 16.7％ (2/12) in 12 patients with KRAS WT,respectively.PTEN was expressed mainly in the nucleus in yellowish brown.The rates of expression in the tissue adjacent to the cancer and in the tumor tissue were 100％ (12/12) and 41.7％ (5/12),respectively.PTEN expression in tumor tissue was reduced or absent.The study indicated that the objective response rate [complete response + partial response (CR + PR)] was 80％ in patients whose KRAS,FCGR,CYP3A5,and CYP1A1 were all in wild type,the CR + PR rates in FCGR,CYP3A5,and CYP1A1 gene mutation group were 0,33.6％ and 50％.The objective response rates of patients with PTEN expression or null were 50％ and 37.5％,respectively (P ＜ 0.05).The progression free survival (PFS) with KRAS/FCGR/CYP3A5/CYP1A1 wild type or mutation were 15.56 or 8.12 months (P ＜ 0.05).The overall survival (OS) with wild type or mutation of KRAS/FCGR/CYP3A5/ CYP1A1 were 25.03 or 19.21 months(P ＜0.05).The PFSs of positive or negative expression of PTEN in patients were 9.13 or 7.87 months (P ＜0.05),and the OSs of positive or negative expression of PTEN in patients were 24.25 or 18.74 months (P ＜0.05).Conclusions FCGR,CYP3A5 and CYP1A1 mutations and PTEN expression null both have been associated with resistance to cetuximab in mCRC patients.FCGR,CYP3A5,CYP1A1 and PTEN can be served as the predictive biomarkers for the response to cetuximab.

Association of CYP1A1z.ast;2C polymorphism with the susceptibility to childhood acute lymphoblastic leukemia: A meta-analysis / 肿瘤

Objective: To explore the contribution of cytochrome P450 (CYP) 1A1z.ast;2C polymorphism to susceptibility to acute lymphoblastic leukemia (ALL) in children. Methods: The case-control studies involving the association of CYP1A1z.ast;2C polymorphism with the susceptibility to childhood ALL were retrieved through computer-based search in PubMed, Embase, Ovid, China Journal Full-text Database, Chinese Biomedical Literature Data, China National Knowledge Infrastructure and Wanfang Database. The statistical analysis was performed by STATA 12.0 software. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated, and the subgroup ananlysis, sensitivity analysis and publication bias were also carried out. Results: A total of seven eligible case-control studies were included for analysis. The Meta analysis revealed that there was a significant association of CYP1A1z.ast;2C ploymorphism with risk of childhood ALL (C vs A: OR = 1.20, 95% CI: 1.01-1.43; GG vs AA: OR = 1.73, 95% CI: 1.1 1-2.70; GG vs AG + AA: OR = 1.68, 95% CI: 1.09-2.59). In a subgroup in which the controls were hospitalized in the same period as the cases hospitalized, there was also a significant association of CYP1A1z.ast;2C ploymorphism with risk of childhood ALL (G vs A: OR = 1.29, 95% CI: 1.04-1.59; GG vs AA: OR = 1.89, 95% CI: 1.15-3.10; GG vs AG+AA: OR = 1.83, 95% CI: 1.14-2.94). After excluding a study with high heterogeneity, the sensitivity analysis showed no significant association between CKP1A1z.ast;2C ploymorphism and childhood ALL. Conclusion: The results of this Meta analysis suggest that CYP1A1z.ast;2C polymorphism may be not significantly associated with the susceptibility to childhood ALL.

Head and Neck Squamous Cell Carcinoma: Genetic Polymorphisms and Occurrence Risks / 한양의대학술지

Head and neck squamous cell carcinoma (HNSCC), which is the 5th most common cancer worldwide, is believed to be induced by environmental carcinogens and host genetic factors. The main etiologic environmental factors are tobacco, alcohol, viral infection, nutritional deficit, mineral inhalation and history of radiation exposure. Accumulating evidence has shown that genetic polymorphisms influence the risk of environmental carcinogenesis, and that genetic susceptibility plays an important role in the development of HNSCC. Genetic susceptibility to HNSCC may be due to genetic polymorphisms in genes controlling both carcinogen metabolism and repair of DNA damage. We analyzed the associations between genetic polymorphisms in the xenobiotics metabolizing gene, alcohol metabolizing gene and DNA repair genes and the risk of HNSCC in an at-risk Korean population. In conclusion, ADH1B +3170A>G His48Arg and XRCC1 R194W (C>T) polymorphism are associated with an increased risk of HNSCC, and these genotypes could be useful biomarkers for identifying Koreans with a greater risk of HNSCC.

Cytochrome P450 1A1 (CYP1A1) polymorphisms and breast ancer risk in Korean women

Cytochrome P450 1A1 (CYP1A1) is involved in the 2-hydroxylation of estrogen, the hormone that plays a critical role in the etiology of breast carcinoma. We evaluated the associations between two CYP1A1 polymorphisms [MspI (rs4646903); Ile462Val (rs1048943)] and breast cancer in a multicenter case-control study of 513 breast cancer cases and 447 controls in Korea. Women carrying the T allele of the CYP1A1 MspI polymorphism were found to have a 1.72-fold (95% CI 1.11-2.68) greater risk of developing breast cancer. No association was found between any CYP1A1 Ile462Val polymorphism and breast cancer. Haplotype analysis of the two loci showed that the CA haplotype was associated with the lowest risk of breast cancer, and CA/CA diplotypes were associated with a lower risk of breast cancer [OR = 0.28 (0.13-0.61)] than others/others diplotypes. Moreover, this reduced risk was more pronounced among women with a lower body mass index (BMI) [OR = 0.18 (0.06-0.58)] or with a shorter lifetime exposure to estrogen [OR = 0.23 (0.07-0.81)]. The results obtained suggest that the CYP1A1 MspI polymorphisms could affect susceptibility to breast cancer.

Polymorphism analysis of CYP1A1 MspI in ovarian cancer / 吉林大学学报(医学版)

Objective To detect the polymorphism of CYP1A1-MspI gene in patients with ovarian cancer.and discuss the relationship between the polymorphism ofCYP1A1-MspI gene and correspond cases' general materials and clinical materials.Methods The free peripheral blood samples of 81 cases confirmed to be ovarian cancer by postoperative pathology were collected preoperatively and the polymorphism of CYP1A1-MspI gene was detected.The clinical materials of the 81 cases with different genotypes were compared.The relationship between the polymorphism and clinical materials was analyzed.Results Among the 81 cases of ovarian cancer,there were 47 cases of wild type-genotype A(T/T)(58%),25 cases of mutation heterozygosis-genotype B(T/C)(31%),and 9 cases of mutation homozygosis-genotype C(C/C)(11%).The genotypic frequency distribution in patients aged from 12 to 29 was one case of genotype A(2.1%),5 cases of genotype B(20.0%),and no case of genotype C.The genotypic frequency distribution in patients aged from 30 to 49 was 12 case of genotype A(25.5%),8 cases of genotype B(32.0%),and 3 cases of genotype C(33.3%).The genotypic frequency distribution in patients aged from 50 to 69 was 31 case of genotype A(66.0%),8 cases of genotype B(32.0%) and 4 cases of genotype C(44.4%).The genotypic frequency distribution in patients aged more than 70 years was 3 case were of genotype A(6.4%),4 cases of genotype B(16.0%),2 case of genotype C(22.2%).There were significant differences of the ages of onset between patients with different CYP1A1-MspI genotypes (P