MTHFR polymorphisms, dietary folate intake and risks to breast cancer / 中华预防医学杂志

<p><b>OBJECTIVE</b>To evaluate the relationship between dietary folate intake and genetic polymorphisms of 5, 10-methylenetetrahydrofolate reductase (MTHFR) with reference to breast cancer risk.</p><p><b>METHODS</b>A case-control study was conducted with 669 cases and 682 population-based controls in Jiangsu province of China. MTHFR C677T and A1298C genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Dietary folate intake was assessed by using an 83-item food frequency questionnaire. Odds ratios (OR) were estimated with an unconditional logistic model.</p><p><b>RESULTS</b>The frequencies of MTHFR C677T C/C, C/T and T/T genotypes were 32.37% (202/624), 48.88% (305/624) and 18.75% (117/624) in cases and 37.66% (235/624), 48.24% (301/624) and 14. 10% (88/624) in controls, respectively. The difference in distribution was significant (chi2 = 6.616, P = 0.037), the T/T genotype being associated with an elevated OR for breast cancer (1.62, 95% CI: 1.14 -2.30). The frequencies of MTHFR A1298C A/A, A/C and C/C were 71.47% (446/624), 27.08% (169/624) and 1.44% (9/624) in cases and 68.11%(425/624), 30.13% (188/624) and 1.76% (11/624)in controls,with no significant differences found (chi2 = 1.716, P= 0.424). Folate intake of cases [(263.00 +/- 137.38) microg/d] was significantly lower than that of controls [(285.12 +/- 149.61) microg/d] (t = -2. 830, P =0.005). Compared with the lowest tertile (< or = 199.08 microg/d) of folate intake, the adjusted OR for breast cancer in the top tertile (> or = 315.11 microg/d) was 0.70 (95% CI: 0.53 -0.92). Among individuals with the MTHFR A1298C A/A genotype,adjusted OR for breast cancer were 0.89 (95% CI: 0.62 - 1.27) and 1.69 (95% CI: 1.20 - 2.36) for the second to the third tertile of folate intake compared with the highest folate intake group (X2trend = 11.372, P = 0.001).</p><p><b>CONCLUSION</b>The findings of the present study suggest that MTHFR genetic polymorphisms,and dietary intake of folate may modify susceptibility to breast cancer.</p>

Genetic polymorphisms of alcohol dehydrogenase-2 and aldehyde dehydrogenase-2 associated with the susceptibility on esophageal cancer / 中华流行病学杂志

Objective To evaluate the impact of alcohol dehydrogenase-2 (ADH2) and aldehyde dehydrogenase-2 (ALDH2) polymorphisms on the susceptibility of esophageal cancer. Methods A case-control study including 221 cases of esophageal cancer and 191 controls was carried out in Taixing city of Jiangsu province. ADH2 and ALDH2 genotypes were tested by PCR and denaturing high -- performance liquid chromatography (DHPLC). Results (1) Compared with ALDH2 G/G carriers, ALDH2 A/A (OR=5.69, 95%CI: 2.51-12.18) and ALDH2 G/A (OR=1.70, 95%CI: 1.08-2.68) carriers showed a significantly elevated risk of developing esophageal cancer, especially among alcohol drinkers with ALDH2 A/A (OR=8.63,95% CI: 2.07-35.95). (2) Statistical relation was not found between ADH2 genotypes and the risk of esophageal cancer, with regard to the status of alcohol consumption. (3) Whether subjects with whatever ADH2 genotype, ALDH2 G/A or A/A carriers was found to have significantly increased the risk of developing esophageal cancer, with ALDH2 A/A carriers appeared having higher esophageal cancer risk than those ALDH2 G/A carriers. (4)Compared those non-drinkers with both ALDH2 G/G and ADH2 A/A , drinkers with ALDH2 G/A or A/A and ADH2 C,/A or G/G genotypes showed a significantly elevated risk of developing esophageal cancer (OR=8.36, 95% CI: 2.98-23.46). Conclusion These results revealed that it was not ADH2 but ALDH2 polymorphisms and drinking alcohol had a significant interaction with the development of esophageal cancer, suggesting that in order to help lowering the risk of esophageal cancer, individuals who are carrying ALDH2 A/A or G/A genotypes should be encouraged to reduce their consumption of alcohols.

Association of Human Leukocyte Antigen Allele Polymorphism and Susceptibility to Children with Acute Lymphocytic Leukemia / 实用儿科临床杂志

Objective To explore the possible association between human leukocyte antigen(HLA) allele polymorphism and susceptibility to chlidren's acute lymphocytic leukemia(ALL).Method HLA alleles polymorphism in 38 cases with ALL and 35 healthy controls were determined by polymerase chain reaction(PCR) with sequence specific olignuleotide probe(PCR/SSO).Results The allele frequency of HLA-A01 significantly increased than control group(?2=4.947 P=0.026,RR=10.20),the frequence of A02 significantly decreased(?2=4.187 P=0.041,RR=3.13),the frequcnce of A33 significunt decreased than control group(?2=4.403 P=0.036,RR=0.21).Conclusion These results show that susceptibility to chlidren's ALL is positively related to HLA-A01,A33,especially A01 allele,while HLA-A33 to its genetic resistance.

HLA-DRB1 allele polymorphosm associated with susceptibility to leukemia in Han nationality of Gansu / 中国实验血液学杂志

The study was aimed to explore the possible association between HLA-DRB1 allele polymorphism and the susceptibility to leukemia in Gansu Chinese Han nationality and to find the genes susceptible to leukemia. HLA-DRB1 genes in 74 patients with leukemia from northwestern China and 82 healthy Chinese controls were determined by polymerase chain reaction and sequence-specific oligonucleotide probe hybridizations (PCR/SSO) DNA analysis. The results showed that as compared with control, the allele frequencies of HLA-DRB1*03 (chi(2) = 8.125, P = 0.004), HLA-DRB1*07 (chi(2) = 13.526, P = 0.000), HLA-DRB1*08 (chi(2) = 18.855, P = 0.000), HLA-DRB1*13 (chi(2) = 7.039, P = 0.008) significantly increased in AML group. The allele frequencies of HLA-DRB1*07 (chi(2) = 5.689, P = 0.017), HLA-DRB1*11 (chi(2) = 7.73, P = 0.005), HLA-DRB1*12 (chi(2) = 4.234, P = 0.040), HLA-DRB1*13 (chi(2) = 38.333, P = 0.000) significantly increased in CML group. The allele frequency of HLA-DRB1*01 (chi(2) = 5.294, P = 0.021) significantly increased in ALL group. It is concluded that the susceptibility to AML in Gansu Han nationality is positively related to HLA-DRB1*03. 1*07.1*08.1*13. CML positively correlates with HLA-DRB1*07. 1*11.1*12.1*13, and ALL may be positively in relation with HLA-DRB1*01. Allele polymorphism is associated with the leukemia occurrence.

JWA gene in regulating committed differentiation of HL-60 cells induced by ATRA, Ara-C and TPA / 中国实验血液学杂志

The study was aimed to explore the role of gene JWA, a novel retinoic acid responsible and cytoskeleton associate gene, in regulating committed differentiation of HL-60 cell and the molecular mechanism in the course of differentiation and apoptosis of leukemic cells. By using FCM, the changes of CD13, CD14, CD15, CD11b and cell cycles were detected in HL-60 cells treated with ATRA (10(-6) mol/L), Ara-C (10 ng/ml) and TPA (10(-8) mol/L) respectively. The samples were determined by semi-quantitative reverse transcript-polymerase chain reaction (RT-PCR) and Western blot for the expression of JWA, Bcl-2, HSP27 and HSP70 at day 0, 2, 4, 6, 8. The results showed that HL-60 cells committedly differentiated into granulocyte-, monocyte-, macrophage-like cells. As a result, JWA was up-regulated in a time-dependent manner, while Bcl-2 was down- regulated at the same time. In ATRA and TPA group, the change of HSP70 had positive correlation with JWA, and negative correlation with Bcl-2. The expression of HSP27 was not detected. Contrast to the cells from APL patient, the expression of JWA need not be activated by ATRA in advance. In this study, we also exposed HL-60 cells in higher dose of Ara-C (20 ng/ml), and JWA expression underwent opposite trend comparing with in lower dose of Ara-C (10 ng/ml). It is concluded that JWA may play double important roles in regulating ATRA and TPA-induced differentiation and apoptosis in leukemic cells. The JWA expression had a negative correlation between induction and cytotoxic response. The difference of JWA expressions between HL-60 cell and ANLL patient cells would be involved in different leukemia pathogenesis.

A case-control study on the polymorphisms of methylenetetrahydrofolate reductase 1298A-->C and susceptibility of esophageal cancer / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between polymorphisms of methylenetetra-hydrofolate reductase gene 1298A-->C (MTHFR 1298A-->C) and its susceptibility of esophageal cancer (EC).</p><p><b>METHODS</b>We conducted a case-control study with 141 cases of EC and 228 population-based controls in Huaian city of Jiangsu province, China. Epidemiological data were collected, and DNA of peripheral blood leukocytes was obtained from all of the subjects. MTHFR genotypes were identified by polymerase chain reaction.</p><p><b>RESULTS</b>(1) The frequency of MTHFR 1298AA, AC and CC genotype were 63.8%, 34.0% and 2.1% in EC and 71.9%, 28.1% and 0.0% in controls, respectively (chi(2)(MH) = 6.69, P = 0.035). The frequency of the MTHFR 1298C allele was 0.19 for EC and 0.14 for controls. (2) Individuals having MTHFR 1298C allele and smoking habit were at a significantly higher risk of developing EC (adjusted OR = 3.48, 95% CI: 1.57 - 7.71) compared with those who having AA genotype but no smoking habit. Individuals having MTHFR 1298C allele and habit of frequent alcohol drinking were at an increased risk of developing EC (adjusted OR = 2.91, 95% CI: 1.20 - 7.08) compared with those with AA genotype and low consumption of alcohol. Individuals having MTHFR 1298C allele but no habit of tea drinking had a 3.52-fold (95% CI: 1.64 - 7.54) increased risk of developing EC compared with tea drinkers with AA genotype. As compared with subjects having AA genotype, low consumption of alcohol, no smoking habit but having habit of drinking tea, the individuals having 1298C allele, habits of frequent alcohol drinking, smoking but no habit of tea drinking had a 12.64-folds (95% CI: 1.39 - 114.65) increased risk of developing EC.</p><p><b>CONCLUSION</b>Results in the present study suggested that there was a coordinated effect between MTHFR 1298 genotypes and habits of smoking, alcohol drinking and tea consumption in the development of EC.</p>

Polymorphism of methylenetetrahydrofolate reductase and sensitivity of stomach cancer to fluoropyrimidine-based chemotherapy / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) C677T or A1298C and the response to fluoropyrimidine (5-FU)-based chemotherapy in advanced stomach cancer (SC).</p><p><b>METHODS</b>75 cases with advanced SC were analyzed. All patients were treated with 5-FU-based chemotherapy and DNA of peripheral blood leukocytes was obtained before therapy. MTHFR genotypes were detected by PCR-RFLP method.</p><p><b>RESULTS</b>(1) Of all the cases, the frequencies of MTHFR C677T C/C, C/T and T/T genotype were 32.0%, 44.0% and 24.0%, while the frequencies of MTHFR A1298C A/A, A/C and C/C genotype were 69.3%, 29.3% and 1.3%, respectively. The overal response rate to 5-FU-based chemotherapy was 29.3%. (2) The response rate to therapy among MTHFR C677T T/T genotype patients (83.3%) was significantly higher than the C677T C/T genotype (15.2%, chi(2) = 22.27, P = 0.000) or the C677T C/C genotype (8.3%, chi(2) = 23.44, P = 0.000). As compared with patients with C677T C allele, patients with C677T T/T genotype had a 7.64-fold sensitivity to 5-FU-based chemotherapy (adjusted for sex, age, prior adjuvant therapy and chemotherapy program, 95% CI: 3.14 - 18.62). The response rate to therapy among patients with MTHFR A1298C A/A genotype (36.5%) was significantly higher than patients with A1298C C allele (13.0%, chi(2) = 4.19, P = 0.041, adjusted OR = 3.75, 95% CI: 0.94 - 14.87). The response rate to therapy among patients with MTHFR C677T T/T and A1298C A/A genotypes (86.7%) was significantly higher than other groups of C677T and A1298C genotypes (15.0%, Fisher exact: P = 0.000, adjusted OR = 6.57, 95% CI: 2.8 - 15.6). (3) The incidence rates of nausea/vomiting in MTHFR C677T T/T, C/T or A1298C A/A genotypes were significantly higher than other genotypes, but the incidence rates of other treatment-related adverse reaction in MTHFR C677T or A1298C genotypes were not significantly different.</p><p><b>CONCLUSION</b>These results in the present study suggested that the polymorphisms of MTHFR were associated with clinical response to 5-FU-based chemotherapy, suggesting that MTHFR genotypes could identify advanced SC patients that would be responsive to 5-FU-based chemotherapy.</p>

The mechanism of JWA gene involved in oxidative stress of cells / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the mechanism of gene JWA involved in oxidative stress under hydrogen peroxide (H(2)O(2)) exposure.</p><p><b>METHODS</b>Both MCF-7 (human breast cancer cell line) and WI-38 (human embryo lung fibroblast cell line) cells were treated with 1 mmol/L of H(2)O(2) with or without pre-incubation of taurine (tau). Malondialdehyde (MDA) and glutathione (GSH) contents in supernatant of cell culture were measured; RT-PCR and Western blotting were carried out for evaluation of the expressions of JWA mRNA and protein respectively. Heat shock proteins (HSP27, HSP70 and HSP90) were also analyzed.</p><p><b>RESULTS</b>The contents of MDA before and after H(2)O(2) treatment in MCF-7 cells were (0.531 +/- 0.038), (0.674 +/- 0.410) mmol/L respectively, (P < 0.01), while those in WI-38 cells were (0.572 +/- 0.035), (0.683 +/- 0.028) mmol/L respectively, (P < 0.01). The contents of GSH before and after H(2)O(2) treatment in MCF-7 cells were (0.053 +/- 0.002), (0.044 +/- 0.002) g/L respectively, (P < 0.01), while those in WI-38 cells were (0.058 +/- 0.002), (0.050 +/- 0.002) g/L respectively, (P < 0.01). The expression of JWA mRNA was down regulated, at 6 h it decreased by 68.4%, while in WI-38 cells no obvious change found. JWA protein and HSP27 showed markedly increased after H(2)O(2) treatment in both cells but not in similar extent.</p><p><b>CONCLUSION</b>Oxidative stress signal pathways of JWA gene varied between cancer and non-cancer cell lines; JWA protein may have a similar function as HSP27 and act as an important signal molecule in H(2)O(2) induced cell injury.</p>

Human eukaryotic translation elongation factor 1 alpha 2 suppresses apoptosis in pancreatic cancer / 中华消化杂志

Objective To explore the potential mechanisms of carcinogenesis for human eukaryotic translation elongation factor 1 alpha 2(EEF1A2).Methods Specific inhibition of EEF1A2 with siRNA was achieved in human pancreatic cancer cell line,BxPC-3,which usually expresses high level of EEF1A2.The changes of EEF1A2 expression were determined by Western blot.The effect of siRNA in suppressing the proliferation of BxPC-3 cells was determined by MTT assay,and its role in inducing BxPC-3 cell apoptosis evaluated by flow cytometry,TUNEL and transmission electron micro- scope.Results The sequence-specific siRNA effectively suppressed the expression of both EEF1A2 mRNA and protein.Specific inhibition of EEF1A2 with siRNA in pancreatic cancer cell line BxPC-3 could suppress proliferation and induce apoptosis.Conclusion The oncogenicity of EEF1A2 may be related to its role in suppressing the apoptosis and promoting the growth of pancreatic cancer cells.