• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3443-3447
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• 2013

Aim: Esophageal cancer is the eighth most common cancer and sixth leading cause of cancer associated death worldwide. The 5 year survival rate for esophageal cancer patients is very poor and accounts for only 12.3%. Besides environmental risk factors, genetic factors might play an important role in the esophageal cancer carcinogenesis. Methods: We conducted a hospital based case-control study to evaluate the genetic effects of functional single nucleotide polymorphisms (SNPs): interleukin 9 (IL9) rs31563 C>T, IL9 rs31564 G>T, IL10 rs1800872 T>G, IL12A rs2243115 T>G, IL12B rs3212227 T>G and IL13 rs1800925 C>T on the development of esophageal cancer. A total of 380 esophageal squamous cell carcinoma (ESCC) cases and 380 controls were recruited for this study. The genotypes were determined using a custom-by-design 48-Plex SNPscan$^{TM}$ Kit. Results: The IL10 rs1800872 T>G polymorphism was associated with an increased risk of ESCC. However, there were no significant links with the other five SNPs. Stratified analyses indicated no significant risk of ESCC associated with the IL10 rs1800872 T>G polymorphism evident among any subgroups. Conclusion: These findings indicated that functional polymorphism IL10 rs1800872 T>G might contribute to ESCC susceptibility. However, our results were obtained with a limited sample size, so that the power of our analysis was low. Future larger studies with more rigorous study designs of other ethnic populations are required to confirm the current findings.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3761-3768
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• 2013

Background: The Saudi population has experienced a sharp increase in colorectal and gastric cancer incidences within the last few years. The relationship between gene polymorphisms of xenobiotic metabolizing enzymes and colorectal cancer (CRC) incidence has not previously investigated among the Saudi population. The aim of the present study was to investigate contributions of CYP1A1, CYP2E1, and GSTM1 gene polymorphisms. Materials and Methods: Blood samples were collected from CRC patients and healthy controls and genotypes were determined by polymerase chain reaction restriction fragment length polymorphism and sequencing. Results and Conclusions: $CYP2E1^*6$ was not significantly associated with CRC development (odd ratio=1.29; confidence interval 0.68-2.45). A remarkable and statistically significant association was observed among patients with $CYP1Awt/^*2A$ (odd ratio=3.65; 95% confidence interval 1.39-9.57). The $GSTM1^*0/^*0$ genotype was found in 2% of CRC patients under investigation. The levels of CYP1A1, CYP2E1 and GSTM1 mRNA gene expression were found to be 4, 4.2 and 4.8 fold, respectively, by quantitative real time PCR. The results of the present case-control study show that the studied Saudi population resembles Caucasians with respect to the considered polymorphisms. Investigation of genetic risk factors and susceptibility gene polymorphisms in our Saudi population should be helpful for better understanding of CRC etiology.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4617-4622
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• 2014

Background: Several studies have previously focused on associations between the (GT)n repeat polymorphism of the heme oxygenase-1 (HO-1) gene promoter region and risk of cancers, but results are complex. We conducted the present meta-analysis to integrate relevant findings and evaluate the association between HO-1(GT)n repeat polymorphism and cancer susceptibility. Materials and Methods: Published literature was retrieved from the PubMed/MEDLINE, EMBASE and ISI Web of Science databases before November 2013. For all alleles and genogypes, odds ratios were pooled to assess the strength of the associations using either fixed-effects or random-effects models according to heterogeneity. Subgroup analysis was conducted according to ethnicity and histopathology. Results: A total of 10 studies involving 2,367 cases and 2,870 controls were identified. The results showed there was no association between HO-1 (GT)n repeat polymorphism and the cancer risk both at the allelic and genotypic level. However, in the stratified analysis, we observed an increased risk of squamous cell carcinoma in persons carrying the LL genotype and the LL+LS genotype as compared with those carrying the SS genotype. When the LS and SS genotypes were combined, the odds ratio for squamous cell carcinoma in LL-genotype carriers, were also significantly increased. No publication bias was observed. Conclusions: The LL genotype and L-allele carrying genotypes (LL+LS) of HO-1 (GT)n repeat polymorphism are potential genetic factors for developing squamous cell carcinoma. More large and well-designed studies are required for further validations.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8815-8822
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• 2014

Background: The incidence of stomach cancer in India is highest in the state of Mizoram. In this population based matched case-control study, we evaluated the relationship between CYP450 2E1 RsaI polymorphism and risk of stomach cancer taking into considering various important dietary habits along with tobacco, alcohol consumption and H. pylori infection status. Materials and Methods: A total of 105 histologically confirmed stomach cancer cases and 210 matched healthy population controls were recruited. CYP2E1 RsaI genotypes were determined by PCR-RFLP and H. pylori infection status by ELISA. Information on various dietary, tobacco and alcohol habits was recorded in a standard questionnaire. Results: Our study revealed no significant association between the CYP2E1 RsaI polymorphism and overall risk of stomach cancer in Mizoram. However, we observed a non-significant protective effect of the variant allele (A) of CYP2E1 against stomach cancer. Tobacco smokers carrying C/C genotype have three times more risk of stomach cancer, as compared to non-smokers carrying C/C genotype. Both Meiziol and cigarette current and past smokers who smoked for more than 10 times per day and carrying the (C/C) genotype are more prone to develop stomach cancer. Smoke dried fish and preserved meat (smoked/sun dried) consumers carrying C/C genotype possesses higher risk of stomach cancer. No significant association between H. pylori infection and CYP2E1 RsaI polymorphism in terms of stomach cancer was observed. Conclusions: Although no direct association between the CYP2E1 RsaI polymorphism and stomach cancer was observed, relations with different tobacco and dietary risk habits in terms of developing stomach cancer exist in this high risk population of north-eastern part of India. Further in-depth study recruiting larger population is required to shed more light on this important problem.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.4
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• pp.1192-1198
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• 2004

Sasang Constitutional Medicine is a major branch of Korean Traditional Medicine. The differences of disease susceptibility to be shown in Sasang constitution may be due to genetic factors. Therefore, I examined interrelationship among cerebral infarction (CI), apolipoprotein E (apo E) gene polymorphism, and Sasang constitutional classification. Apo E is a key protein modulating the highly atherogenic apoB containing lipoproteins and is a candidate gene for the development of coronary artery disease (CAD). The ε2 and/or ε4 alleles were the first to be implicated in premature CAD, which resulted in this polymorphism being extensively studied. I investigated the association between apo E genotype and CI by case-control study in a Korean population. I also classified CI patients and control group into groups according to Sasang Constitutional Medicine. 218 CI patients and 379 controls without CI were examined. Apo E genotype was determined by 8% polyacrylamide gel separation after DNA amplification. A frequency of apo E ε3/ε3 in the apo E genotype distribution was higher in the CI patients compared with that in controls. Also, it was widely known that Taeumin was easily attacked with CI, but there was no association between apo E polymorphim and Taeumin. However, the Taeumin constitution did not enhance the relative risk for CI in the subjects with apo E ε2 and/or ε4 alleles. No differences in the apo E genotypes frequencies were observed in the Taeumin compared with that in the other constitutions. In addition, I investigated whether the DD(deletion/deletion) or ID(insertion/deletion) genotype of angiotensin converting enzyme (ACE) gene, a candidate gene for CI, was associated with CI, Taeumin constitution, and apo E polymorphism. As a result, the frequency of Taeumin constitution was significantly higher in CI patients with both apo E ε3/ε4 and ACE ID/DD genotypes than in the remaining Sasang constitutions. In summary, it was concluded that the apo E polymorphism is a major risk factor for CI in Koreans and the ACE ID/DD genotype enhanced the relative risk for CI in the subjects with apo E ε3/ε4 genotype and Taeumin constitution.

• Advances in Traditional Medicine
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• v.4 no.2
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• pp.104-111
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• 2004

Sasang Constitutional Medicine is a major branch of Korean Traditional Oriental Medicine. The differences of disease susceptibility to be shown in Sasang constitution may be due to genetic factors. Therefore, we examined interrelationship among cerebral infarction (CI), apolipoprotein E (apoE) gene polymorphism, and Sasang constitutional classification. ApoE is a key protein modulating the highly atherogenic apoB containing lipoproteins and is a candidate gene for the development of coronary artery disease (CAD). The ${\varepsilon}2\;and/or\;{\varepsilon}4$ alleles were the first to be implicated in premature CAD, which resulted in this polymorphism being extensively studied. We investigated the association between apoE genotype and CI by case-control study in a Korean population. We also classified CI patients and control group into groups according to Sasang Constitutional Medicine. 196 CI patients and 379 controls without CI were examined. ApoE genotype was determined by 8% polyacrylamide gel separation after DNA amplification. A significant difference in the apoE genotype distribution was observed in the CI patients compared with that in controls ($X^{2}$=14.920, df=4, P=0.005). Also, the frequency of Taeumin constitution in patients with CI was significantly higher than that in controls (58.0% vs. 36.9%; P<0.001). However, the Taeumin constitution did not enhance the relative risk for CI in the subjects with apoE ${\varepsilon}2\;and/or\;{\varepsilon}4$ alleles. No differences in the apoE genotypes frequencies were observed in the Taeumin compared with that in the other constitutions. In addition, we investigated whether the DD genotype of angiotensin converting enzyme (ACE) gene, a candidate gene for CI, was associated with CI, Taeumin constitution, and apoE polymorphism. As a result, the frequency of Taeumin constitution was significantly higher in CI patients with both apoE ${\varepsilon}3/{\varepsilon}4$ and ACE ID/DD genotypes than in the remaining Sasang constitutions (14.5% vs. 8.3% and 0%) ($X^{2}$=13.521, df=6, P=0.035). In summary, we concluded that the apoE polymorphism is a major risk factor for CI in Koreans and the ACE ID/DD genotype enhanced the relative risk for CI in the subjects with apoE ${\varepsilon}3/{\varepsilon}4$ genotype and Taeumin constitution.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2597-2604
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• 2012

Methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme involved in folate metabolism; a single nucleotide polymorphism (SNP) C677T has been reported to be linked with altered incidences of several diseases. We here conducted a meta-analysis of 15 published epidemiological studies with a total of 7306 cases and 8062 controls to evaluate its association with prostate cancer risk with overall and subgroup analyses. No statistical relationship was found overall with any genetic model (TT vs. CC: OR = 0.80, 95%CI = [0.62, 1.04], P = 0.094; CT vs. CC: OR = 0.97, 95%CI = [0.84; 1.12], P = 0.667; Dominant: OR = 0.94, 95%CI = [0.82; 1.07], P = 0.343; Recessive: OR = 0.81, 95%CI = [0.64; 1.04], P = 0.104), but after the exclusion of several studies, we could observe the homozygote TT to confer less susceptibility to prostate cancer in carriers; moreover, different effects of the polymorphism on prostate cancer risk was detected from subgroup analysis stratified by participants' residential region: significant reduced prostate cancer risk was found to be associated with the polymorphism from Asian studies (TT vs. CC: OR = 0.47, 95%CI = [0.33; 0.67], P < 0.001; CT vs. CC: OR = 0.73, 95%CI = [0.60; 0.90], P = 0.002; Dominant: OR = 0.67, 95%CI = [0.56; 0.82], P < 0.001; Recessive: OR = 0.55, 95%CI = [0.40; 0.76], P < 0.001) while studies from Europe indicated a slight increased risk under dominant model with marginal significance (OR = 1.14, 95%CI = [0.99; 1.30], P = 0.064). Moreover, the protective effect of the polymorphism against prostate cancer was also shown by studies performed in yellow Asians (TT vs. CC: OR = 0.48, 95%CI = [0.31; 0.75], P = 0.001; CT vs. CC: OR = 0.68, 95%CI = [0.51; 0.90], P = 0.006; Dominant: OR = 0.63, 95%CI = [0.48; 0.82], P < 0.001; Recessive: OR = 0.57, 95%CI = [0.39; 0.84], P = 0.004). We propose that these phenomena should be viewed with the consideration of folate metabolism profile and different gene background as well as living habits of different populations, and more relevant studies should be conducted to confirm our hypothesis and provide a comprehensive and clear picture concerning this topic.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.21 no.2
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• pp.116-122
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• 2011

Human occupational exposure to n-hexane has been associated with neurobehavioral symptoms such as depression, irritablity, acute irritation symptom, concentration disturbance and fatigue. Effects of monoamine oxidase (MAO) B and serotonin transporter receptor (5-HTTR) polymorphisms on the neurobehavioral symptoms were investigated in 70 male workers from TV and computer monitor manufacturing plants exposed to n-hexane. Neurobehavioral symptoms were assessed through a self-reported questionnaire and ambient level of n-hexane was measured by NIOSH method. Blood and urine were collected from each workers to determine the MAO(B), 5-HTTR and urinary 2,5-hexanedione(2,5-HD). The mean concentration of volatile n-hexane was $18.8{\pm}28.8ppm$ and that of urinary 2,5-HD was $1.07{\pm}1.47mg/g$ creatinine. Statistically significant associations with sexual disturbance were age and smoking. The frequencies of MAO(B) AA, AG and GG were 18.6%, 45.7% and 35.7%, respectively, and the frequencies of 5-HTTR ll, ls and ss genotype were 82.9%, 15.7% and 1.4%, respectively. MAO (B) gene polymorphisms had susceptibility to the neurobehavioral symptoms such as fatigue, concentration disturbance, irritability and acute irritation symptom and 5-HTTR gene polymorphism had susceptibility to the sleep disturbance and acute irritation symptom. On multiple logistic regression analysis for the neurobehavioral symptoms, memory disturbance was significantly associated with smoking(OR=6.752, 95% CI=37.46) and drinking(OR=4.033, 95% CI=1.252-12.98), emotional lability was MAO(B) genotype(OR=0.412, 95% CI=0.170-0.996), fatigue (OR=1.011, 95% CI=1.000-1.021) and acute irritation(OR=0.990, 95% CI=0.981-1.000) were working duration and sexual disturbance were significantly associated with age(OR=1.208, 95% CI=1.042-1.399), ambient n-hexane(OR=1.077, 95% CI=1.005-1.154) and 2,5-HD(OR=0.186, 95% CI=0.041-0.841). This finding implies that the MAO (B) and 5-HTTR polymorphisms may affect susceptibility for specific neurobehavioral symptoms associated with n-hexane exposure in workers.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5777-5783
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• 2012

Published data on the associations between tumor necrosis factor-alpha (TNF-${\alpha}$) promoter -308G>A and -238G>A polymorphisms and cervical cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Data were collected from MEDLINE and PubMed databases. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated in a fixed/random effect model. 13 separate studies including 3294 cases and 3468 controls were involved in the meta-analysis. We found no association between TNF-${\alpha}$-308G>A polymorphism and cervical cancer in overall population. In subgroup analysis, significantly elevated risks were found in Caucasian population (A vs. G: OR = 1.43, 95% CI = 1.00-2.03; AA vs. GG: OR = 2.09, 95% CI = 1.34-3.25; Recessive model: OR = 2.09, 95% CI = 1.35-3.25) and African population (GA vs. GG: OR = 1.53, 95% CI = 1.02-2.30). An association of TNF-${\alpha}$-238G>A polymorphism with cervical cancer was found (A vs. G: OR = 0.61, 95% CI = 0.47-0.78; GA vs. GG: OR = 0.59, 95% CI = 0.45-0.77; Dominant model: OR = 0.59, 95% CI = 0.46-0.77). When stratified by ethnicity, similar association was observed in Caucasian population (A vs. G: OR = 0.62, 95% CI = 0.46-0.84; GA vs. GG: OR = 0.59, 95% CI = 0.43-0.82; Dominant model: OR = 0.60, 95% CI = 0.44-0.83). In summary, this meta-analysis suggests that TNF-${\alpha}$-238A allele significantly decreased the cervical cancer risk, and the TNF-${\alpha}$-308G>A polymorphism is associated with the susceptibility to cervical cancer in Caucasian and African population.

• Journal of the Korean Chemical Society
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• v.50 no.2
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• pp.123-128
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• 2006

Behcet's disease (BD) is a systemic vasculitis characterized by recurrent oral and genital ulcers, and ocular inflammation, and which may involve the joints, skin, central nervous system and gastrointestinal tract. Although the exact pathogenesis for BD is not completely understood, it has been suggested that the disease is triggered in genetically susceptible individuals by environmental factors, such as microbial agents. It is noted that multiple genes, including MHC (major histocompatibility complex) and non-MHC genes, are implicated in the pathogenesis of BD. This study tries to determine whether IL-6 gene polymorphisms are associated with susceptibility to Behcet's disease in Koreans. Gene polymorphisms were typed by VNTR (variable number of tandem repeat), RFLP (restriction fragment length polymorphism), DHPLC (denaturing high performance liquid chromatography).There were no evidences for genetic association conferred by the IL-6prom polymorphism. However, significant differences in the IL-6vntr genotype and allele frequencies were found between patients with BD and controls. The IL-6vntr*C allele appeared to be an additional susceptibility gene to Korean BD. Further studies in other populations and gene are required to confirm these results.