• Asian Pacific Journal of Cancer Prevention
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• 제17권2호
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• pp.739-742
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• 2016

Risks with GSTM1 genotypes and potential roles of smoking in the susceptibility to oral squamous cell carcinoma (OSCC) were studied in Northeastern Thailand. Study subjects were 79 histologically-confirmed OSCC cases (31 men, 48 women) and 79 age- and sex-matched healthy controls ranging in age from 25 to 84 years. GSTM1 genotyping was achieved by two independent PCR assays. The GSTM1 null allele and the homozygous genotype did not increase risk of OSCC vs the wild type allele and the remaining genotypes. When the focus was on the smoking habit, male subjects who smoked ${\geq}10$ or ${\geq}35$ years were at significantly increased risk for OSCC with adjusted ORs of 4.88 [95%CI, 1.41-16.87, p=0.012] or 4.94 [95%CI, 1.62-15.12, p=0.005], respectively. A higher risk for OSCC was found for smoking amount; those who smoked >5 or >10 pack-years were at a higher risk with adjusted OR of 4.46 [95%CI; 1.45-13.74, p=0.009] or 3.89 [95%CI; 1.34-11.28, p=0.012], respectively. There are certain smoking patterns that give greater risks and thus both smoking duration and pack-years should be taken into consideration in tobacco related cancer prevention.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2025-2029
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• 2012

Objective: Methylenetetrahydrofolate reductase (MTHFR) catalyzes the metabolism of folate and nucleotides needed for DNA synthesis and repair. Variations in MTHFR functions likely play roles in the etiology of lung cancer (LC). So far, several studies between MTHFR C677T polymorphism and LC provide controversial or inconclusive results. Methods: To better assess the purported relationship, we performed a meta-analysis of 14 publications. Eligible studies were identified by searching the Pubmed, Embase, Web of Science and Google Scholar databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. Results: Overall, no significant association was detected between the MTHFR C677T polymorphism and LC risk, the same as in race subgroup. However, in the stratified analysis by histological type, significantly increased non-small-cell lung cancer (NSCLC) risk was indicated (T-allele vs. C-allele: OR = 1.11, 95%CI = 1.03-1.19; TT vs. CC: OR = 1.24, 95%CI = 1.09-1.41; TC vs. CC: OR = 1.11, 95%CI = 1.03-1.20 and TT+TC vs. CC: OR = 1.09, 95%CI = 1.03-1.15). At the same time, ever-smokers who carried T-allele (TT+TC) had a 10% decreased LC risk compared with CC genotype carriers. Conclusions: Our study provided evidence that the MTHFR 677T null genotype may increase NSCLC risk, however, it may protect ever-smokers against LC risk. Future studies with large sample sizes are warranted to further evaluate this association in more detail.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6131-6136
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• 2014

Objective: Epidemiology studies have reported conflicting results between glutathione S-transferase Mu-1 (GSTM1), glutathione S-transferase theta-1 (GSTT1) and glutathione S-transferase pi-1 (GSTP1) and ovarian cancer (OC) susceptibility. In this study, an updated meta-analysis was applied to determine whether the deletion of GSTM1, GSTT1 and GSTP1 has an influence on OC susceptibility. Methods: A published literature search was performed through PubMed, Embase, Cochrane Library, and Science Citation Index Expanded database for articles published in English. Pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated using random or fixed effects models. Heterogeneity between studies was assessed using the Cochrane Q test and $I^2$ statistics. Sub-group analysis was conducted to explore the sources of heterogeneity. Sensitivity analysis was employed to evaluate the respective influence of each study on the overall estimate. Results: In total, 10 published studies were included in the final analysis. The combined analysis revealed that there was no significant association between GSTM1 null genotype and OC risk (OR=1.01, 95%CI: 0.91-1.12). Additionally, there was no significant association between GSTT1 genetic polymorphisms and OC risk (OR=0.98, 95% CI: 0.85-1.13). Similalry, no significant associations were found concerning the GSTP1 rs1695 locus and OC risk. Meanwhile, subgroup analysis did not show a significant increase in eligible studies with low heterogeneity. However, sensitivity analysis, publication bias and cumulative analysis demonstrated the reliability and stability of the current meta-analysis. Conclusions: These findings suggest that GSTs genetic polymorphisms may not contribute to OC susceptibility. Large epidemiological studies with the combination of GSTM1 null, GSTT1 null and GSTP1 Ile105Val polymorphisms and more specific histological subtypes of OC are needed to prove our findings.

• Genomics & Informatics
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• 제5권2호
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• pp.61-67
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• 2007

The allele frequencies of markers as well as linkage disequilibrium (LD) can be changed in cases due to the LD between markers and the disease allele, exhibiting spurious associations of markers. To identify the true association, classical statistical tests for dealing with confounders have been applied to draw a conclusion as to whether the association of variants comes from LD with the known disease allele. However, a more direct test considering LD using estimated haplotype frequencies may be more efficient. The null hypothesis is that the different allele frequencies of a variant between cases and controls come solely from the increased disease allele frequency and the LD relationship with the disease allele. The haplotype frequencies of controls are estimated using the expectation maximization (EM) algorithm from the genotype data. The estimated frequencies are applied to calculate the expected haplotype frequencies in cases corresponding to the increase or decrease of the causative or protective alleles. The suggested method was applied to previously published data, and several APOE variants showed association with Alzheimer's disease independent from the APOE ${\varepsilon}4$ variant, rs429358, regardless of LD showing significant simulated p-values. The test results support the possibility that there may be more than one common disease variant in a locus.

• 한국환경성돌연변이발암원학회지
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• 제22권4호
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• pp.303-311
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• 2002

This study evaluated the concentrations of urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) in industrial waste incineration workers. The effect of genetic polymorphisms of xenobiotic metabolism enzymes on urinary concentration of PAH metabolites was assessed. And, aromatic DNA adduct levels were also determined in total white blood cells. Fifty employees were recruited from a company handling industrial wastes located in Ansan, Korea: non-exposed group (n=21), exposed group (n=29). Sixteen ambient PAHs were determined by GC/MSD (NIOSH method) from personal breathing zone samples of nine subjects near incinerators. Urinary 1-hydroxypyrene glucuronide (1-OHPG), a major pyrene metabolite, was assayed by synchronous fluorescence spectroscopy after immunoaffinity purification using monoclonal antibody 8E11 (SFS/IAC). Multiplex PCR was used for genotyping for GSTMI/TI and PCR-RFLP for genotyping of CYP1A1 (MspI and Ile/Val). PAH-DNA adducts in peripheral blood WBC were measured by the nuclease P1-enhanced postlabeling assay. Smoking habit, demographic and occupational information were collected by self-administered questionnaire. The range of total ambient PAH levels were 0.00-7.00 mg/㎥ (mean 3.31). Urinary 1-OHPG levels were significantly higher in workers handling industrial wastes than in those with presumed lower exposure to PAHs (p=0.006, by Kruskal-Wallis test). There was a statistically significant dose-response increase in 1-OHPG levels with the number of cigarettes consumed per day (Pearson correlation coefficient=0.686, p<0.001). Urinary 1-OHPG levels in occupationally exposed smoking workers were highest compared with non-occupationally exposed smokers (p=0.053, by Kruskal-Wallis test). Smoking and GSTMI genotype were significant predictors for log-transformed 1-OHPG by multiple regression analysis (overall model R²=0.565, p<0.001), whereas smoking was the only significant predictor for log-transformed aromatic DNA adducts (overall model R²=0.249, p=0.201). Aromatic DNA adducts was also a significantly correlation between log transferred urinary 1-OHPG levels (pearson's correlation coefficient=0.307, p=0.04). However, the partial correlation coefficient adjusting for Age, Sex, and cigarette consumption was not significant (r=0.154, p=0.169). The significant association exists only in individuals with the GSTMI null genotype (pearsons correlation coefficient=0.516, p=0.010; partial correlation coefficient adjusting for age, sex, and cigarette consumption, r=0.363, p=0.038). Our results suggest that the significant increase in urinary 1-OHPG in the exposed workers is due to higher prevalence of smokers among them, and that the association between urinary PAH metabolites and aromatic DNA adducts in workers of industrial waste handling may be modulated by GSTMI genotype. There results remain to be confirmed in future larger studies.

• Asian Pacific Journal of Cancer Prevention
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• 제17권3호
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• pp.1215-1219
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• 2016

Background: Worldwide, breast cancer is the most common cancer among women and is a leading cause of cancer death. In the present study, we investigated the NQO1 C609T genotypic and allelic distribution in north Indian breast cancer patients. Materials and Methods: The genotypic distribution of the NQ01 C609T polymorphism was assessed in 100 invasive ductal carcinoma (IDC) breast cancer patients and 100 healthy controls using allele specific PCR (AS-PCR). Results: A lower frequency of the CC genotype was found in breast cancer patients (24%) than in the controls. On the other hand, TT genotype frequency was also found to be higher in female healthy controls (32%) than the female breast cancer patients (20%). The frequencies of all three genotypes CC, CT, TT in patients were 24%, 56% and 20% and in healthy controls 50%, 22% and 32% respectively. We did not find any significant correlation between the NQO1 C609T polymorphism and age group, grading, menopausal status and distant metastasis. A less significant association was found between the NQ01 C609T polymorphism and the stage of breast cancer (X2=5.931, P=0.05). Conclusions: The present study shows a strong association between NQO1 C609T polymorphism with the breast cancer risk in the north Indian breast cancer patients so that possible use as a risk factor should be further expel.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6673-6680
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• 2013

Objective: Insulin resistance (IR) is an established risk factor for colorectal cancer (CRC). Given that CRC and IR physiologically overlap and the calpain-10 gene (CAPN10) is a candidate for IR, we explored the association between CAPN10 and CRC risk. Methods: Blood samples of 400 case-control pairs were genotyped, and the lifestyle and dietary habits of these pairs were recorded and collected. Unconditional logistic regression (LR) was used to assess the effects of CAPN10 SNP43 and SNP19, and environmental factors. Both generalized multifactor dimensionality reduction (GMDR) and the classification and regression tree (CART) were used to test gene-environment interactions for CRC risk. Results: The GA+AA genotype of SNP43 and the Del/Ins+Ins/Ins genotype of SNP19 were marginally related to CRC risk (GA+AA: OR = 1.35, 95% CI = 0.92-1.99; Del/Ins+Ins/Ins: OR = 1.31, 95% CI = 0.84-2.04). Notably, a high-order interaction was consistently identified by GMDR and CART analyses. In GMDR, the four-factor interaction model of SNP43, SNP19, red meat consumption, and smoked meat consumption was the best model, with a maximum cross-validation consistency of 10/10 and testing balance accuracy of 0.61 (P < 0.01). In LR, subjects with high red and smoked meat consumption and two risk genotypes had a 6.17-fold CRC risk (95% CI = 2.44-15.6) relative to that of subjects with low red and smoked meat consumption and null risk genotypes. In CART, individuals with high smoked and red meat consumption, SNP19 Del/Ins+Ins/Ins, and SNP43 GA+AA had higher CRC risk (OR = 4.56, 95%CI = 1.94-10.75) than those with low smoked and red meat consumption. Conclusions: Though the single loci of CAPN10 SNP43 and SNP19 are not enough to significantly increase the CRC susceptibility, the combination of SNP43, SNP19, red meat consumption, and smoked meat consumption is associated with elevated risk.

• Asian-Australasian Journal of Animal Sciences
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• 제22권7호
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• pp.943-954
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• 2009

Diacylglycerol acyltransferase (DGAT) is a key enzyme that catalyzes the final and rate-limiting step of triglyceride synthesis. Both DGAT1 and DGAT2 genes code proteins with DGAT activity. Studies have shown DGAT1 polymorphisms associate with intramuscular fat deposition in beef cattle, but fewer associations between DGAT2 and beef cattle economic traits have been reported. The objective of this study was to investigate single nucleotide polymorphism (SNP) in intron3 of bovine DGAT2 and evaluate the associations of that with carcass, meat quality, and fat yield traits. Test animals were 157 commercial feedlot steers belonging to 3 Chinese native breeds (22 for Luxi, 24 for Jinnan, and 23 for Qinchuan), 3 cross populations (20 for Charolais${\times}$Fuzhou, 18 for Limousin ${\times}$Luxi, and 17 for Simmental${\times}$Jinan) and 1 Taurus pure breed population (16 Angus steers). In the current study, 15 SNP were discovered in intron3 and exon4 of DGAT2 at positions 65, 128, 178, 210, 241, 255, 270, 312, 328, 334, 365, 366, 371, 415, and 437 (named as their positions in PCR amplified fragments). Only 7 of them (128, 178, 241, 270, 312, 328, and 371) were analyzed, because SNP in three groups (65-128-255, 178-210-365 and 241-334-366) were in complete linkage disequilibrium within the group, and SNP 415 was a deletion and 437 was a null mutation. Frequencies for rare alleles in the 3 native breed populations were higher than in the 3 cross populations for 178 (p = 0.04), 270 (p = 0.001), 312 (p = 0.03) and 371 (p = 0.002). A general linear model was used to evaluate the associations between either SNP genotypes or allele substitutions and the measured traits. Results showed that SNP 270 had a significant association with the fat yield associated with kidney, pelvic cavity, heart, intestine, and stomach (KPHISY). Animals with genotype CC and CT for 270 had less (CC: -7.71${\pm}$3.3 kg and CT: -5.34${\pm}$2.5 kg) KPHISY than animals with genotype TT (p = 0.02). Allele C for 270 was associated with an increase of -4.26${\pm}$1.52 kg KPHISY (p = 0.006) and $-0.92{\pm}0.45%$ of retail cuts weight percentage (NMP, Retail cuts weight/slaughter body weight) (p = 0.045); allele G for 312 was associated with an increase of -5.45${\pm}$2.41 kg KPHISY (p = 0.026). An initial conclusion was that associations do exist between DGAT2 gene and carcass fat traits. Because of the small sample size of this study, it is proposed that further effort is required to validate these findings in larger populations.

• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.3253-3260
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• 2014

Background: A case-control study was conducted to evaluate the effect of household exposure, dietary habits, smoking and Glutathione S-Transferases M1, T1 polymorphisms on lung cancer among women in Mizoram, India. Materials and Methods: We selected 230 newly diagnosed primary lung cases and 460 controls from women in Mizoram. Multivariate logistic regression analysis was performed to estimate adjusted odds ratio (OR). Results: Exposure of cooking oil fumes (p<0.003), wood as heating source for cooking (p=0.004), kitchen inside living room (p=0.001), improper ventilated house (p=0.003), roasting of soda in kitchen (p=0.001), current smokers of tobacco (p=0.043), intake of smoked fish (p=0.006), smoked meat (p=0.001), Soda (p<0.001) and GSTM1 null genotype (p=0.003) were significantly associated with increased risk of lung cancer among women in Mizoram. Significantly protective effect was observed for intake of bamboo shoots (p=<0.001) and egg (p<0.001). A clear increase in dose response gradient was observed for total cooking dish years. Risk for lung cancer tends to increase with collegial effect of indoor environmental sources (p=0.022). Significant correlation was also observed for interaction of GST polymorphisms with some of dietary habits. Conclusions: We confirmed the important role of exposure of cooking oil emission and wood smoke, intake of smoked meat, smoked fish and soda (an alkali preparation used as food additives in Mizoram) and tobacco consumption for increase risk of lung cancer among Women in Mizoram.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제28권5호
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• pp.364-371
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• 2002

Many chemical compopunds are converted into reactive electrophilic metabolites by the oxidative(Phase I) enzymes, which are mainly cytochrome P-450 enzyme(CYPs). Phase II conjugating enzymes, such as glutathione S-transferase(GST), usually act as inactivation of enzymes. Genetic polymorphisms have been found to be associated with increased susceptibility to cancer of the lung, bladder, breast and colorectal. Many of the polymorphic genes of carcinogen metabolism show considerably different type of cancer among different ethnic groups as well as individuals within the same group. The aim of this study is (1) to establish the frequencies of genetic polymorphisms of GSTM1 and CYP1A1 in Korean oral squamous cell carcinoma(SCC), (2) to associate oral SCC with the risk of these genetic polymorphisms. The genetic polymorphisms of the GSTM1 and the CYP1A1 genes among 50 Korean oral SCC were analyzed using polymerase chain reaction(PCR). The results suggest that the homozygote and the mutant type of CYP1A1 MspI polymorphisms may be associated with genetic susceptibility to oral SCC in Korean. A combination of the GSTM1 null type with the homozygote(m1/m1), and the mutant(m2/m2) type of CYP1A1 MspI polymorphisms showed a relatively high risk of oral SCC in Korean. In the smoking group, the GSTM1 wild genotype may be the high risk factor of oral SCC in Korean. These data coincide with the hypothesis which states that different susceptibility to cancer of genetic polymorphisms exist among different ethnic group and different types of human cancer.