Leukocyte immunoglobulin-like receptor A3 gene deletion in five Chinese populations and protective association with nasopharyngeal carcinoma.

Among the thirteen leukocyte Ig-like receptor (LILR) loci located at 19q13.4, LILRA3 is unique in that it encodes a soluble protein lacking the transmembrane and cytoplasmic domains, and a 6.7 kb deletion spanning the first seven exons has been detected in some human individuals. Presently, there is a lack of data about the distribution of LILRA3 gene deletion in more diverse ethnic groups. Also, no previous studies have investigated the correlation between copy number variation (CNV) of LILRA3 and nasopharyngeal carcinoma (NPC). In this study, five populations from China mainland: two Southern Han populations, Hunan (N = 1478) and Guandong (N = 107); one Southeastern Han population, Fujian (N = 439); and two Northern populations, Inner Mongolia Han (N = 104) and Mongol population from Inner Mongolia (N = 158) were investigated for CNV of LILRA3 using polymerase chain reaction-sequence-specific priming (PCR-SSP) method. LILRA3 variants were also examined in a cohort of NPC cases (N = 1142) in Hunan Han population. The five Chinese populations demonstrated northward increase in frequency of the deleted form of LILRA3 gene (LILRA3*Del) (all corrected p values < 0.05). Inter-population comparison also uncovered significant differentiation in the distribution of CNV of LILRA3 among modern human populations. LILRA3*Del was found to confer significantly reduced risk to NPC in Hunan Han population (at allelic level: OR = 0.79, 95% CI = 0.71-0.89, p < 0.0001; at genotype level: OR = 0.63, 95% CI = 0.51-0.79, p < 0.0001). No interaction was found between LILRA3 variants and HLA-A*02:07, HLA-A*11:01, HLA-B*13 and HLA-B*46:01 alleles in susceptibility to NPC. Our study constitutes the first demonstration of LILRA3 gene as a locus linked to NPC susceptibility in a southern Chinese population. Future independent studies in other populations are warranted to confirm the findings reported in this study.

Magnetic fluid hyperthermia induced by radiofrequency capacitive field for the treatment of transplanted subcutaneous tumors in rats.

Magnetic fluid hyperthermia (MFH) induced by a magnetic field has become a new heating technology for the treatment of malignant tumors due to its ability to heat the tumor tissue precisely and properly, and due to its significant therapeutic effects. In this study, MFH induced by radiofrequency capacitive field (RCF) for the treatment of transplanted subcutaneous tumors in rats, was investigated. A total of 50 rats bearing subcutaneous tumors were randomly divided into five groups, including i) a pseudo-treatment (PT) control group, ii) magnetic fluid (MF) group, iii) pure hyperthermia (PH) group, iv) magnetic fluid hyperthermia 1 (MFH1) group, and v) magnetic fluid hyperthermia 2 (MFH2) group. Tumors were irradiated for 30 min in the MFH1 group 24 h following injection of MF. Tumors were irradiated for 30 min in the MFH2 group 24 h following injection of MF, and irradiation was repeated for 30 min 72 h following injection of MF. Tumor volumes, tumor volume inhibition ratios and survival times in the rat model were examined. Temperatures of tumor cores and rims both rapidly reached the desired temperature (∼50°C) for tumor treatment within 5 to 10 min in the MFH1 and MFH2 groups, and we maintained this temperature level by manually adjusting the output power (70-130 W). Tumor volumes of the MFH1 and MFH2 groups were reduced compared to those of the PT, MF and PH groups. The inhibitory effect on tumor growth in the MFH2 group (91.57%) was higher compared to that in the MFH1 group (85.21%) and the other groups. The survival time of the MFH2 group (51.62±2.28 days) and MFH1 group (43.10±1.57 days) was increased compared to that of the PH, MF and PT groups. The results obtained show that MFH induced by RCF may serve as a potential and promising method for the treatment of tumors.

Predictive value of Xrcc1 gene polymorphisms for side effects in patients undergoing whole breast radiotherapy: a meta-analysis.

Radiation-induced side effects on normal tissue are determined largely by the capacity of cells to repair radiation-induced DNA damage. X-ray repair cross-complementing group 1 (XRCC1) plays an important role in the repair of DNA single-strand breaks. Studies have shown conflicting results regarding the association between XRCC1 gene polymorphisms (Arg399Gln, Arg194Trp, -77T>C and Arg280His) and radiation-induced side effects in patients undergoing whole breast radiotherapy. Therefore, we conducted a meta-analysis to determine the predictive value of XRCC1 gene polymorphisms in this regard. Analysis of the 11 eligible studies comprising 2,199 cases showed that carriers of the XRCC1 399 Gln allele had a higher risk of radiation-induced toxicity than those with the 399 ArgArg genotype in studies based on high-quality genotyping methods [Gln vs. ArgArg: OR, 1.85; 95% CI, 1.20-2.86] or in studies with mixed treatment regimens of radiotherapy alone and in combination with chemotherapy [Gln vs. ArgArg: OR, 1.60; 95% CI, 1.09-2.23]. The XRCC1 Arg399Gln variant allele was associated with mixed acute and late adverse reactions when studies on late toxicity only were excluded [Gln allele vs. Arg allele: OR, 1.22; 95% CI, 1.00-1.49]. In contrast, the XRCC1 Arg280His variant allele was protective against radiation-induced toxicity in studies including patients treated by radiotherapy alone [His allele vs. Arg allele: OR, 0.58; 95% CI, 0.35-0.96]. Our results suggest that XRCC1 399Gln and XRCC1 280Arg may be independent predictors of radiation-induced toxicity in post-surgical breast cancer patients, and the selection of genotyping method is an important factor in determining risk factors. No evidence for any predictive value of XRCC1 Arg194Trp and XRCC1 -77T>C was found. So, larger and well-designed studies might be required to further evaluate the predictive value of XRCC1 gene variation on radiation-induced side effects in patients undergoing whole breast radiotherapy.

Gender-specific associations between MICA-STR and nasopharyngeal carcinoma in a southern Chinese Han population.

Previous studies have identified several HLA-B specificities that are associated with nasopharyngeal carcinoma (NPC) in populations of Chinese descent, in particular HLA-B35, -B38, -B46, and -B58. Perhaps except for HLA-B46, other associations cannot be simply accounted for by the linkage disequilibrium between HLA-A and B loci. The human major histocompatibility complex (MHC) class I chain-related gene A (MICA) maps 46 kb centromeric to HLA-B and is highly polymorphic; it encodes a stress-inducible protein which functions as a ligand for the NKG2D/DAP10 complex to activate natural killer (NK) cells, gammadelta T cells, and CD8(+) T cells. We postulated MICA gene as a susceptibility factor for nasopharyngeal carcinoma, an Epstein-Barr virus-associated malignancy. In this study, 218 unrelated patients newly diagnosed with NPC and 196 randomly selected healthy controls from southern China mainland were analyzed for the short tandem repeat polymorphism of exon 5 of MICA gene (MICA-STR) and MICA gene deletion, using fluorescent polymerase chain reaction-gene scanning (PCR/size-sequencing) and polymerase chain reaction-sequence-specific priming (PCR/SSP) technology. MICA*A9 was present at significantly increased frequency in the patient group (P (C)=0.0001002, OR=2.528, 95% CI=1.636-3.907), whereas the frequency of MICA*A5.1 was significantly decreased (P (C)=0.006, OR=0.594, 95% CI=0.437-0.806). Gender-based stratification revealed a significant increase of MICA*A9 frequency (P (C)=0.000072, OR=3.255, 95% CI=1.855-5.709) and a significant decrease of MICA*A5.1 frequency (P (C)=0.000737, OR=0.486, 95% CI=0.337-0.702) in male patients with NPC (N=166), compared with male normal controls (N=120). A significant interaction between MICA*A9 and gender was observed ([see text]=41.58, P=0.0001). Statistics also revealed heterogeneity of effects among MICA*A5.1/MICA*A9-bearing phenotypes and a dose-dependent effect of MICA*A5.1 and MICA*A9 on NPC risk in male subgroup. This constitutes the first demonstration of a gender-specific association between MICA-STR polymorphism and NPC, which could largely be attributable to the underlying gender-related mechanisms that modulate MICA gene expression. The results provide strong supporting evidence suggesting that MICA*A9 may be a genetic risk factor for NPC in male individuals in this population. The potential interaction between MICA and other non-HLA host factors and environmental exposures remains to be further studied.

[Polymorphism of short tandem repeat of exon 5 of MHC class-I chain related gene A and association with nasopharyngeal carcinoma in a southern Chinese population].

OBJECTIVE: To explore the association between the short tandem repeat polymorphism of exon 5 of MICA gene (MICA-STR) and nasopharyngeal carcinoma (NPC) in a southern Chinese population. METHODS: One hundred and twenty-seven consecutive NPC patients and 112 randomly selected normal controls residing in southern China mainland were analyzed for MICA-STR allelic variation and MICA gene deletion by fluorescent polymerase chain reaction-gene scanning and polymerase chain reaction-sequence specific priming. RESULTS: MICA*A9 was observed at significantly higher frequency in the NPC patient group than in the control group (relative risk = 2.524, P = 0.001,Pc = 0.006); whereas MICA*A5.1 was present at significantly lower frequency in the NPC patient group than in the control group (RR = 0.418, P = 0.0004, Pc = 0.0026). Further analysis revealed that MICA*A9 was over-represented in male NPC patients, compared with male controls (RR = 3.23, P = 0.00095, Pc = 0.006); whereas MICA*A5.1 was present at significantly lower frequency in male NPC patients, compared with male controls (RR = 0.372, P = 0.0007, Pc = 0.004). None of the MICA-STR variants showed statistically significant frequency difference between female NPC patients and female controls (Pc > 0.05). CONCLUSION: MICA-STR polymorphism is associated with NPC, and MICA*A9 is a genetic susceptibility marker of male individuals for NPC in a southern Chinese population.