[Association of the Thr241Met polymorphism of DNA repair gene XRCC3 with genetic susceptibility to AFB1-related hepatocellular carcinoma in Guangxi population].

OBJECTIVE: To explore the association of the Thr241Met polymorphism of X-ray cross-complementing group 3 (XRCC3) gene with genetic susceptibility to aflatoxin B1(AFB-1)-related hepatocellular carcinoma (HCC)in Guangxi population. METHODS: We conducted a hospital-based case-control study, including 257 HCC cases and 711 controls without cancers or liver diseases. The XRCC3 Thr241Met polymorphism was analyzed by PCR. RESULTS: The XRCC3 genotypes XRCC3-Thr/Met or XRCC3-Met/Met were related with an elevated risk of HCC. The risk of HCC was associated with the number of mutant Met copies (adjusted OR were 2.20 and 8.56 for XRCC3-Thr/Met and Met/Met, respectively); moreover, there seemed to be combined effects for HCC risk between the variant genotypes and AFB1-DNA adduct levels from peripheral blood leukocytes (adjusted OR was 2.34 to 20.44, P < 0.01). CONCLUSION: These results suggested that XRCC3 polymorphism may be associated with the risk of AFB1- related HCC among the Guangxi population, and interacts with AFB1 exposure in the development of HCC induced by AFB1.

[A study about the association of detoxication gene GSTM1 polymorphism and the susceptibility to aflatoxin B1-related hepatocellular carcinoma].

OBJECTIVES: To investigate the association between susceptibility to aflatoxin B1(AFB1)-related hepatocellular carcinoma (HCC) and the polymorphism of detoxication gene GSTM1. METHODS: The peripheral white blood cell DNA samples were obtained from all the subjects including 140 HCC cases and 536 controls from an AFB1 high risk area in Guangxi province. The GSTM1 polymorphism was detected using PCR technique. RESULTS: (1) The GSTM1-present was associated with a decreased HCC risk. The GSTM1-null was associated with an increased HCC risk [adjusted OR (95% CI)= 2.07 (1.20-3.57)]. (2) In the cohorts of both low/median and high exposure levels of AFB1, GSTM1-null genotype was associated with a conspicuous significantly increased risk for HCC [adjusted OR (95% CI) = 1.92 (0.92-4.00) and 1.80 (0.77-4.17)]. CONCLUSION: The results suggest that genetic polymorphism of GSTM1 was susceptible to HCC and individuals who are GSTM1-null have an increased risk of developing HCC. There is evidence of interaction between GSTM1 polymorphism and AFB1 exposure, especially with low/median degrees of AFB1 exposure.

Polymorphism of glutathione S-transferase mu 1 and theta 1 genes and hepatocellular carcinoma in southern Guangxi, China.

AIM: Glutathione S-transferase mu 1 (GSTM1) and theta 1 (GSTT1) genes are involved in the metabolism of a wide range of carcinogens, but deletions of the genes are commonly found in the population. The present study was undertaken to evaluate the association between GSTM1 and GSTT1 gene polymorphisms and hepatocellular carcinoma (HCC) risk. METHODS: The genetic polymorphisms were studied at an aflatoxin highly contaminated region in Guangxi, China. Polymerase chain reaction (PCR) technique was used to detect the presence or absence of the GSTM1 and GSTT1 genes in blood samples. The case group was composed of 181 patients of HCC identified by the pathologists and the control group was composed of 360 adults without any tumor. RESULTS: The frequencies of GSTM1 and GSTT1 null genotypes in the control were 47.8% and 42.7%, while those in the HCC group were 64.6% and 59.7%, respectively. The differences between HCC group and control group were very significant (P<0.01). GSTM1 and GSTT1 combined null genotypes in HCC group and control group were 38.2% and 18.5% respectively, and the difference was significant (P<0.05). CONCLUSION: The GSTM1 and GSTT1 null genotypes are associated with an increased risk of HCC in a special geographic environment. Combination of the two null genotypes in an individual is substantially increased twice the risk of HCC.

[Study on the detoxication gene gstM1-gstT1-null and susceptibility to aflatoxin B1 related hepatocellular carcinoma in Guangxi].

OBJECTIVE: To study the association between susceptibility to aflatoxin B1 (AFB1)-related hepatocellular carcinoma(HCC) and the null genotypes of detoxication gene gstM1 and gstT1. METHODS: Peripheral blood white blood cells DNA samples were obtained from all the subjects including 140 HCC cases and 536 controls from AFB1 high risk area Guangxi. gstM1 and gstT1 polymorphisms were detected by polymerase chain reaction technique. RESULTS: (1) gstM1- and gstT1-present were associated with decreasing risk of HCC. gstM1- and gstT1-null were associated with the increasing risk of HCC [adjusted OR (95 % CI) = 2.07 (1.20-3.57) and 1.44 (0.85-2.45), respectively]; (2) The appearance of both gstM1- and gstT1-null genotypes were more susceptible to HCC than either one of them(adjusted OR and 95% CI are 2.43 and (1.19-4.97); (3) From low/median to high level of AFB1 exposure, both gstM1- and gstTl-null genotypes were associated with significantly conspicuous increasing risk of HCC [adjusted OR(95% CI) = 12.76(5.38-30.24) and 7.82(3.61-16.90) respectively]. CONCLUSION: It was suggested that: genetic polymorphisms of gstM1 and gstT1 were susceptible to HCC; individuals who were gstM1- or gstT1-null would have an increasing risk of developing HCC while individuals with both nulls were more susceptible. There was evidence of interaction between gstM1- and gstT1-null and the level of AFB1 exposure which was associated with the increasing risk of HCC.

[Expression of DeltaNp63 protein in nasopharyngeal carcinoma and its significance].

BACKGROUND & OBJECTIVE: The molecular etiology of nasopharyngeal carcinoma is currently unknown. It was reported that DeltaNp63 is dominant-negative toward transactivation of p53, and associated with the malignant hyperplasia and dedifferentiation of the squamous cells. This study was designed to investigate the expression and significance of DeltaNp63 protein in NPC tissues. METHODS: Immunohistochemical method was used to determine the expression of DeltaNp63 in 60 cases of NPC, 37 cases of nearby mucosa of the carcinoma, and 30 cases of chronic inflammation of nasopharyngeal mucosa. The classification of the 60 NPC cases were as follows: 3 cases of keratinizing squamous cell carcinomas, 57 cases of nonkeratinizing carcinomas including 12 cases of undifferentiated carcinomas. RESULTS: All 60 NPC cases showed DeltaNp63 positive reaction. Keratinizing squamous cell carcinomas showed weakly positive expression; 66.67% (38/57) of nonkeratinizing carcinomas showed strongly positive reaction, and 83.33% (10/12) of undifferentiated carcinomas showed strongly positive reaction. Chronic inflammation mucosas and cancer nearby mucosas showed positive reaction only in their basal and superbasal cells. CONCLUSION: DeltaNp63 protein was found to be closely associated with cell malignant hyperplasia. DeltaNp63 protein has distinct tendency to the infantile or anaplastic squamous cells, and DeltaNp63 protein is a valuable diagnostic marker for anaplastic squamous cells.

[Frequent genetic deletion of detoxifying enzyme GSTM1 and GSTT1 genes in nasopharyngeal carcinoma patients in Guangxi Province, China].

OBJECTIVE: To study the genetic susceptibility to chemical carcinogens of nasopharyngeal carcinoma (NPC) patients in a high-risk area in Guangxi. METHODS: PCR technique was used to examine the frequency of glutathione S-transferase M1 and T1 gene deletion in a matched case-control study of 91 patients with NPC and 135 control subjects. RESULTS: The deletion frequency of control subjects was 47.4% (65/135) for GSTM1 and 40.7% (55/135) for GSTT1, whereas that of NPC patients was 61.5% (56/91) for GSTM1 and 59.3% (54/91) for GSTT1 with statistically significant difference between the patients and the controls (P < 0.05 and P < 0.01). Furthermore, the frequency of codeletion of both genes was also higher in NPC patients than the control with statistically significant difference (chi2 = 12.533, P = 0.002). CONCLUSION: In high-risk area, nasopharyngeal carcinoma patients and local residents have high frequency of GSTM1 and/or GSTT1 gene deletion. It suggests that a genetic susceptibility to putative chemical carcinogens may be responsible for NPC clustering in the high-risk area studied.

Aflatoxin sufferer and p53 gene mutation in hepatocellular carcinoma.

AIM:To study the p53 gene mutation and its relationship to aflatoxin B1 exposure in hepatocellular carcinoma (HCC).METHODS: Restriction fragment length polymorphism analysis method was used in 62 HCC samples, and DNA direct sequencing in another 45 HCC samples.RESULTS: In HCC and AFB1 high and low-risk areas, 36/52 (69%) and 2/10 (20%) cases were found losing the HaeIII allele respectively, suggesting one of the base G mutation at the p53 gene codon 249. Similar results appeared in DNA direct sequencing, 20/35 (57%) and 1/10 (10%) respectively mutated at the codon 249 third base G to C transversion.CONCLUSION: In HCC after AFB1 exposure, mutation of p53 gene is fixed at codon 249 third base and take the form of G to T transversion. This is a definite marker of mutation which is induced by AFB1 mutagen. It is applicable for molecular epidemiologic survey of the sufferers of AFB1 among HCC cases and for discovering more unknown natural AFB1 contaminated areas.