• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5767-5772
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• 2015

Background: Polymorphisms in the MDM2 309 (T>G) and TP53 72 (G>C) genes are reported to increase the susceptibility to head and neck cancer (HNC) in various populations. The risk for HNC is also strongly associated with etiologic habits such as smoking, alcohol consumption and/or chewing of betel quid (BQ). In a case-control study, we investigated the significance of the above polymorphisms alone, and upon interaction with one another as well as with various etiologic habits in determining HNC risk in a Northeast Indian population. Materials and Methods: Genotyping at 309 MDM2 and 72 TP53 in 122 HNC patients and 86 cancer free healthy controls was performed by PCR using allele specific primers, and the results were confirmed by DNA sequencing. Results: Individuals with the GG mutant allele of MDM2 showed a higher risk for HNC in comparison to those with the TT wild type allele (OR=1.9, 95%CI: 1.1-3.3) (p=0.022). The risk was further increased in females by ~4-fold (OR=4.6, 95% CI: 1.1-19.4) (P=0.04). TP53 polymorphism did not contribute to HNC risk alone; however, interaction between the TP53 GC and MDM2 GG genotypes resulted in significant risk (OR=4.9, 95% CI: 0.2-105.1) (p=0.04). Smokers, BQ- chewers and alcohol consumers showed statistically significant and dose-dependent increase in HNC risk, irrespective of the MDM2 genotype. Conclusions: MDM2 genotype could serve as an important predictive biomarker for HNC risk in the population of Northeast India.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3461-3464
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• 2012

Methotrexate (MTX) is an important drug for the treatment of childhood acute lymphoblastic leukemia (ALL). However, related toxicity occurs in many organs which may cause interruption of treatment, morbidity, and mortality. Single nucleotide polymorphisms (SNPs) of dihydrofolate reductase (DHFR) and gamma glutamyl hydrolase (GGH) are known to alter their enzymatic activity and thus affect the metabolism of MTX and influence the effectiveness. Therefore, we hypothesized that genetic variations of DHFR and GGH genes may influence the risk of toxicity after high dose MTX. The study population comprised of 105 children with ALL who were treated according to the modified St Jude Total XV protocol. The patients received 2.5 or $5g/m^2$ of MTX for 5 doses during the consolidation phase. Genotyping of DHFR 829C>T and GGH-401C>T was performed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The GGH-401CT and TT genotypes were associated with increased risk of leukopenia and thrombocytopenia after high dose MTX (OR 2.97, 95%CI; 1.24-7.13 and OR 4.02, 95%CI; 1.58-10.26). DHFR 829C>T was not associated with toxicity. In conclusion, the GGH-401CT and TT genotypes were found to increase the risk of severe leukopenia and thrombocytopenia after exposure to high dose MTX for childhood ALL therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3047-3052
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• 2012

The enzyme encoded by the MGMT gene is involved in the repair of alkylated lesions formed in DNA by carcinogenic nitrosamines. Since dietary items consumed by the Kashmiri population contain high concentrations of these agents, it is biologically plausible that MGMT polymorphic variants may be associated with their risk of esophageal cancer. The present study was performed to assess whether non-synonymous SNPS at codon Leu84Phe and codon Ileu143Val of the MGMT gene, close to the active site of the protein, might be linked to predisposition of Kashmiris to esophageal cancer. Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism on 92 cases and 77 healthy controls. Codon 84 and codon 143 SNPs of the MGMT gene were not associated with any increase in risk. While the frequency of the Phe allele at codon 84 in cases was (0.16), slightly higher than controls (0.12), the difference was not statistically significant. Similarly, the frequency of Valine allele in cases at codon 143 (0.08) and controls (0.09) was nearly equal. Moreover, no significant association of MGMT genotypes with the clinicopatholgic variables of esophageal cancer patients was observed. In conclusion, MGMT variants at codon 84 and codon143 may not be involved in the susceptibility of the Kashmiri population to esophageal cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.12
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• pp.5195-5201
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• 2016

Background: Brain tumors, constituting one of the most deadly forms of cancer worldwide, result from the accumulation of multiple genetic and epigenetic alterations in genes and signaling pathways. Isocitrate dehydrogenase enzyme isoform 1 (IDH1) mutations are frequently identified in primary brain tumors and acute myeloid leukemia. Studies on IDH1 gene mutations have been extensively performed in various populations worldwide but not in Malaysia. This work was conducted to study the prevalence of IDH1 c.395G>A (R132H) hotspot mutations in a group of Malaysian patients with brain tumors in order to gain local data for the IDH1 mutation profile in our population. Methods: Mutation analysis of c.395G>A (R132H) of IDH1 was performed in 40 brain tumor specimens by the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) and then verified by direct sequencing. Associations between the IDH1 c.395G>A (R132H) mutation and clinicopathologic characteristics were also analyzed. Results: The IDH1 c.395G>A (R132H) mutation was detected in 14/40 patients (35%). A significant association was found with histological tumor types, but not with age, gender and race. Conclusions: IDH1 is frequently mutated and associated with histological subtypes in Malay brain tumors.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5069-5074
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• 2012

Objectives: The purpose of this study was to determine the relationship between methylation status of the Dact1 gene and MTHFR a1298c polymorphic forms in transitional cell carcinoma tissues in a Chinese population. Methods: Polymorphisms of folate metabolism enzyme gene MTHFR were assessed by restrictive fragment length polymorphism (RFLP) methods and PCR-based DNA methylation analysis was used to determine the CpG island methylation status of the Dact1 gene. Associations between the methylation status of the Dact1 gene and clinical characteristics, as well as MTHFR a1298c polymorphisms, were analyzed. Results: aberrant methylation of the Dact1 gene was found in 68.3% of cancer tissues and 12.4% of normal tissues,. The methylation rate of the Dact1 gene in cancer tissues was significantly higher in patients with lymph node metastasis than in those without lymph node metastasis (46.3% vs. 17.2%, P = 0.018). No association was found between aberrant DNA methylation and selected factors including sex, age, tobacco smoking, alcohol consumption and green tea consumption. After adjusting for potential confounding variables, variant allele of MTHFR a1298c was found to be associated with methylation of the Dact1 gene. Compared with wild type CC, the odds ratio was 4.33 (95% CI: 1.06-10.59) for AC and 4.95 (95% CI: 1.18-12.74) for AA. The N stage in TNM staging and the occurrence of lymph node metastasis were associated with an MTHFR 1298 AA+AC genotype (P<0.05). Conclusion: MTHFR 1298 AC and AA genotypes might help maintain a normal methylation status of the Dact1 gene, aberrant CpG island methylation of which is closely related to the genesis and progression of transitional cell carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1799-1802
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• 2012

Objective: We aimed to analyze the association between excision repair cross-complementing rodent repair deficiency complementation group 1 (XRCC1) and ovarian cancer risk. Methods: We performed a hospital-based case-control study with 155 cases and 313 controls in China. All Chinese cases with newly diagnosed primary ovarian cancer between May 2005 to May 2010 in our hospital were invited to participate within 2 months of diagnosis. Controls were randomly selected from people who requested general health examinations in the same hospital during the same period. SNPs in EXCC1, ERCC1 C8092A and ERCC1 T19007C, were analyzed by PCR-RFLP method. Results: We observed a non-significantly increased risk of ovarian cancer among individuals with ERCC1 8092TT compared with those with the 8092CC genotype (adjusted OR=1.55, 95% CI%=0.74-2.97). Moreover, 19007TT genotype carriers also showed a non-significant increased risk of ovarian cancer over those with the 19007CC genotype (adjusted OR=1.78, 95% CI%=0.91-3.64). Conclusion: Our firstly investigation of links between polymorphisms in the ERCC1 gene and the risk of ovarian cancer in Chinese population demonstrated no significant association. Further large sample studies in Chinese populations are needed.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2199-2206
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• 2012

Background: Our objective was to evaluate the MTHFR C677T-A1298C polymorphisms in patients with breast cancer and in individuals with no history of cancer, to compare the levels of genetic damage and apoptosis under folic acid (FA) deficiency between patients and controls, and to assess associations with breast cancer. Methods: Genetic damage was marked by micronucleated binucleated cells (MNBN) and apoptosis was estimated by cytokinesis-block micronucleus assay (CBMN). PCR-RFLP molecular analysis was carried out. Results: The results showed significant associations between the MTHFR 677TT or the combined MTHFR C677T-A1298C and breast cancer risk (OR = 2.51, CI = 0.85 to 7.37, p = 0.08; OR = 4.11, CI = 0.78 to 21.8, p < 0.001). The MNBN from the combined MTHFR C677T-A1298C was higher and the apoptosis was lower than that of the single variants (p < 0.05). At 15 to 60 nmol/L FA, the MNBN in cases with the TTAC genotype was higher than controls (p < 0.05), whereas no significant difference in apoptosis was found between the cases and controls after excluding the genetic background. Conclusions: Associations between the combined MTHFR C677T-A1298C polymorphism and breast cancer are possible from this study. A dose of 120 nmol/L FA could enhance apoptosis in cases with MTHFR C677T-A1298C. Breast cancer individuals with the TTAC genotype may be more sensitive to the genotoxic effects of FA deficiency than controls.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.4923-4926
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• 2012

Aim: To investigate whether XRCC1 and ADPRT polymorphisms might be associated with outcomes of breast cancer. Methods: A prospective study was conducted with a total of 335 breast cancer patients undergoing chemotherapy consecutively collected from Jan. 2005 to Jan. 2008. Genotyping of XRCC1 and ADPRT polymorphisms was conducted by PCR-RFLP assay. Results: All 335 patients were followed up until death or the end of Jan. 2012, with a median follow-up period of 38.8 (2-64) months. It was shown that the variant genotype of XRCC1 399Gln/Gln was strongly significantly associated with a decreased risk of death from breast cancer, with an HR (95% CI) of 0.52 (0.28-0.91). Similarly, individuals carrying the ADPRT 762Ala/Ala demonstrated longer survival compared to ADPRT 762 Val/Val, with an HR (95% CI) of 0.58 (0.31-0.97). Individuals with combination genotypes of XRCC1 399Gln allele and ADPRT 762Ala/Ala presented with a longer survival, the HR (95% CI) being 0.56 (0.32-0.97). Conclusion: We found a significant association between XRCC1399Gln/Gln and ADPRT 762Ala/Ala polymorphisms and clinical outcomes. These two genotypes could be used as a surrogate markers of clinical outcome in glioma cases receiving chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3391-3394
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• 2016

Background: Helicobacter pylori is now recognized as a causative factor of chronic gastritis, gastroduodenal ulcers, gastric cancer and mucosa-associated lymphatic tissue lymphoma. Toll-like receptors are important bacterial receptors in gastric epithelial cell signaling transduction and play critical roles in gastric carcinogenesis. Materials and Methods: A total of 400 patients undergoing esophagogastroduodenoscopy for investigation of chronic abdominal pain were genotyped for single-nucleotide polymorphisms (SNPs) in TLR1 (rs4833095) using TagMan SNPs genotyping assay by real-time PCR hybridization. Relationships with susceptibility to H. pylori infection and pre-malignant gastric mucosa morphological patterns, classified by magnifying NBI endoscopy, were investigated. Results: The percentages of TLR1 rs4833095, CC homozygous, CT heterozygous and TT homozygous cases were 34, 46.5 and 19%, respectively. CC showed statistical differences between H. pylori positive and negative cases (P<0.001). CT and TT correlated with type 1 and type 2 gastric mucosal morphological patterns (P <0.01) whereas CC correlated with types 3 and 4 (P<0.01). Conclusions: This study demonstrated good correlation of TLR1 rs4833095 genotype with severity of inflammation in H. pylori infected gastric mucosa according to gastric mucosal morphologic patterns with magnifying NBI endoscopy.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.781-784
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• 2013

Aim: The purpose of this study was to determine whether susceptibility to oral tongue squamous cell carcinoma (OSCC) is related to polymorphisms in the u-PA gene. Methods: We examined the rs2227564 C/T and rs2227562 G/A single nucleotide polymorphisms (SNPs) in 196 OSCC patients and 201 age- and gender-matched controls via direct sequencing and PCR-RFLP methods. Results: Significant differences were found in allelic and genotypic distributions of the rs2227564 and rs2227562 loci when comparing cases and controls. In addition, logistic analyses indicated that the rs2227564 C/T genotype was related to a 1.52-fold increased risk of developing OSCC (adjusted OR=1.521, 95%CI: 1.144~2.022, P=0.004). Linkage disequilibrium analysis was conducted and no association between the two loci was found (D'=0.031, $r^2$=0.000). Conclusions: Our findings provide evidence that the rs2227564 C/T SNP in the u-PA gene is associated with the development of OSCC.