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Updated Meta-analysis of the Association Between CYP2E1 RsaI/PstI Polymorphisms and Lung Cancer Risk in Chinese Population

  • Wang, Ya-Dong;Yang, Hai-Yan;Liu, Jing;Wang, Hai-Yu
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.13
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    • pp.5411-5416
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    • 2014
  • Background: A number of studies have reported relationships of CYP2E1 RsaI/PstI polymorphisms with susceptibility to lung cancer in Chinese population. However, the epidemiologic results have been conflictive rather than conclusive. The purpose of this study was to address the associations of CYP2E1 RsaI/PstI polymorphisms with lung cancer risk in Chinese population comprehensively. Materials and Methods: Systematic searches were conducted in the PubMed, Science Direct, Elsevier, CNKI and Chinese Biomedical Literature Databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of association. Results: Overall, we observed a decreased lung cancer risk among subjects carrying CYP2E1 RsaI/PstI c1/c2 and c1/c2+c2/c2 genotypes (OR=0.76, 95%CI: 0.64-0.90 and OR=0.78, 95%CI: 0.66-0.93, respectively), as compared with subjects carrying the c1/c1 genotype. In subgroup analysis, we observed a decreased lung cancer risk among c1/c2 carriers in hospital-based studies (OR=0.81, 95%CI: 0.68-0.98) and among carriers with c1/c2 and c1/c2+c2/c2 genotypes in population-based studies(OR=0.57, 95%CI: 0.42-0.79 and OR=0.58, 95%CI: 0.43-0.79, respectively), as compared with subjects carrying the c1/c1 genotype. Limiting the analysis to studies with controls in Hardy-Weinberg equilibrium (HWE), we similarly observed a decreased lung cancer risk among c1/c2 and c1/c2+c2/c2 carriers (OR=0.73, 95%CI: 0.60-0.88 and OR=0.73, 95%CI: 0.60-0.88, respectively), as compared with c1/c1. Conclusions: Our results suggested that CYP2E1 RsaI/PstI c1/c2 and c1/c2+c2/c2 variants might be a protective factor for developing lung cancer in Chinese population. Further well-designed studies with larger sample size are required to verify our findings.

Pin1 Promoter rs2233678 and rs2233679 Polymorphisms in Cancer: A Meta-analysis

  • Zhu, Yan-Mei;Liu, Jing-Wei;Xu, Qian;Yuan, Yuan
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.5965-5972
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    • 2013
  • PIN1 is one member of the parvulin PPIase family. By controlling Pro-directed phosphorylation, PIN1 plays an important role in cell transformation and oncogenesis. There are many polymorphisms in the PIN1 gene, including rs2233678 and rs2233679 affecting the PIN1 promoter. Recently, a number of case-control studies were conducted to investigate the association between PIN1 gene rs2233678 and rs2233679 polymorphism and cancer risk. However, published data are still conflicting. In this paper, we summarized data for 5,427 cancer cases and 5,469 controls from 9 studies and attempted to assess the susceptibility of PIN1 gene polymorphism to cancers by a synthetic meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the relationship. All analyses were performed using Stata software. Our results suggested that rs2233678 represented a protective factor in overall analysis (CC vs GG: OR= 0.697, 95%CI: 0.498-0.976; CG vs GG: OR=0.701, 95%CI: 0.572-0.858; Dominant model: OR= 0.707, 95%CI: 0.590-0.847; C allele vs G allele: OR=0.734, 95%CI: 0.623-0.867) and especially for squamous cell carcinoma of the head and neck, lung cancer and breast cancer in Asians and Caucasians. The rs2233679 polymorphism was significantly associated with decreased cancer risk in overall analysis (CT vs CC: OR=0.893, 95%CI=0.812-0.981; Dominant model: OR=0.893, 95%CI=0.816-0.976; T allele vs C allele; OR=0.947, 95%CI=0.896-1.000) and especially in Asians. In conclusion, our meta-analysis suggested that -842G>C (rs2233678) and -667C>T (rs2233679) may contribute to genetic susceptibility for cancer risks. Further prospective research with larger numbers of worldwide participants is warranted to draw comprehensive and firm conclusions.

Comparison of the Efficacy and Safety of EFGR Tyrosine Kinase Inhibitor Monotherapy with Standard Second-line Chemotherapy in Previously Treated Advanced Non-small-cell Lung Cancer: a Systematic Review and Meta-analysis

  • Qi, Wei-Xiang;Shen, Zan;Lin, Feng;Sun, Yuan-Jue;Min, Da-Liu;Tang, Li-Na;He, Ai-Na;Yao, Yang
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.10
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    • pp.5177-5182
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    • 2012
  • Purpose: To compare the efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitormonotherapy (EFGR-TKIs: gefitinib or erlotinib) with standard second-line chemotherapy (single agent docetaxel or pemetrexed) in previously treated advanced non-small-cell lung cancer (NSCLC). Methods: We systematically searched for randomized clinical trials that compared EGFR-TKI monotherapy with standard second-line chemotherapy in previously treated advanced NSCLC. The end points were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), 1-year survival rate (1-year SR) and grade 3 or 4 toxicities. The pooled hazard ratio (HR) or risk ratio (RR), with their corresponding 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. Results: Eight randomized controlled trials (totally 3218 patients) were eligible. Our meta-analysis results showed that EGFR-TKIs were comparable to standard second-line chemotherapy for advanced NSCLC in terms of overall survival (HR 1.00, 95%CI 0.92-1.10; p=0.943), progression-free survival (HR 0.90, 95%CI 0.75-1.08, P=0.258) and 1-year-survival rate (RR 0.97, 95%CI 0.87-1.08, P=0.619), and the overall response rate was higher in patients who receiving EGFR-TKIs(RR 1.50, 95%CI 1.22-1.83, P=0.000). Sub-group analysis demonstrated that EGFR-TKI monotherapy significantly improved PFS (HR 0.73, 95%CI: 0.55-0.97, p=0.03) and ORR (RR 1.96, 95%CI: 1.46-2.63, p=0.000) in East Asian patients, but it did not translate into increase in OS and 1-year SR. Furthermore, there were fewer incidences of grade 3 or 4 neutropenia, febrile neutropenia and neutrotoxicity in EGFR-TKI monotherapy group, excluding grade 3 or 4 rash. Conclusion: Both interventions had comparable efficacy as second-line treatments for patients with advanced NSCLC, and EGFR-TKI monotherapy was associated with less toxicity and better tolerability. Moreover, our data also demonstrated that EGFR-TKImonotherapy tended to be more effective in East Asian patients in terms of PFS and ORR compared with standard second-line chemotherapy. These results should help inform decisions about patient management and design of future trials.

Association Between VDR Polymorphisms and Breast Cancer: An Updated and Comparative Meta-analysis of Crude and Adjusted Odd Ratios

  • Huang, Qian-Qian;Liao, Yu-Yi;Ye, Xiao-Hua;Fu, Jin-Jian;Chen, Si-Dong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.2
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    • pp.847-853
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    • 2014
  • There is a lot of debate on the relationship between vitamin D receptor polymorphisms and risk of breast cancer. Herein, we quantitatively analyzed the published case-control studies on this relationship by meta-analysis, performing a bibliographic search from Pubmed and CNKI up to July 31, 2013. The included case-control studies for Fok1, Bsm1, Taq1, Apa1, Cdx2 and Poly-A were 16, 19, 20, 10, 4, 6, respectively. Crude and adjusted odd ratios and 95% confidence intervals were calculated to present and compare the strength of any associations. The results of combined analyses indicated that Fok1, Bsm1, Apa1, Cdx2 and Poly-A were not significantly associated with the risk of breast cancer. In contrast, the tt genotype of Taq1 was a modest risk factor for breast cancer development (tt vs. TT: OR = 1.21, 95% CI: 1.01-1.44). To further confirm the above results, adjusted effects for the six polymorphisms were pooled based on adjusted ORs reported in the original studies. Adjusted ORs of Fok1, Apa1, Cdx2 and Poly-A were similar to the crude ORs. However, Bsm1 and Taq1 showed inconsistent results. For Bsm1, OR for BB vs. bb was 0.85, 95% CI: 0.74-0.98; for Taq1, OR for tt vs. TT was 1.03, 95% CI: 0.92-1.15, and not associated with risk. Subgroup analyses for crude ORs showed some association between Bsm1, Taq1 and breast cancer in Caucasians only, but for adjusted ORs, no associations were found. This meta-analysis suggests that the roles that Fok1, Apa1, Cdx2 and Poly-A polymorphisms play in breast cancer risk are negligible, with Bsm1 and Taq1 as possible exceptions. To be conservative, we still assumed that they may play a modest role in determining breast cancer risk. Further studies are needed to validate our findings.

Impact of Chronic Hepatitis B and Hepatitis C on Adverse Hepatic Fibrosis in Hepatocellular Carcinoma Related to Betel Quid Chewing

  • Jeng, Jen-Eing;Tsai, Meng-Feng;Tsai, Hey-Ru;Chuang, Lea-Yea;Lin, Zu-Yau;Hsieh, Min-Yuh;Chen, Shinn-Chern;Chuang, Wan-Lung;Wang, Liang-Yen;Yu, Ming-Lung;Dai, Chia-Yen;Tsai, Jung-Fa
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.2
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    • pp.637-642
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    • 2014
  • The pathogenesis of hepatocellular carcinoma (HCC) related to habitual betel quid (BQ) chewing is unclear. Risk of HCCis increased with adverse hepatic fibrosis. This study aimed to assess the impact of chronic viral hepatitis on adverse hepatic fibrosis in HCC related to BQ chewing. This hospital-based case-control study enrolled 200 pairs of age- and gender-matched patients with HCC and unrelated healthy controls. Serologic hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus (anti-HCV), ${\alpha}$-fetoprotein (AFP), and surrogate markers for significant hepatic fibrosis were measured. Information on substance-use habits was obtained with a questionnaire. By analysis of surrogate markers for hepatic fibrosis, the prevalence of significant hepatic fibrosis in patients chewing BQ was between 45.8% and 91.7%, whereas that for patients without BQ chewing was between 18.4% and 57.9%. The difference was significant (P <0.05 for each surrogate marker). Multivariate analysis indicated that cirrhosis with Child-Pugh C (odds ratio (OR) = 3.28; 95% confidence interval (CI), 1.29-8.37), thrombocytopenia (OR = 3.92, 95% CI, 1.77-8.68), AFP >400 mg/L (OR = 2.21, 95% CI, 1.05-4.66) and male gender (OR = 4.06, 95% CI, 1.29-12.77) were independent factors associated with habitual BQ chewing. In conclusion, adverse hepatic fibrosis and severe liver damage play important roles in the pathogenesis of BQ-related HCC, which could be aggravated by chronic hepatitis B and hepatitis C. BQ-cessation programs and prevention of chronic HBV/HCV infection are needed to prevent HCC related to BQ chewing.

A Population-based Case-control Study on Risk Factors for Gastric Cardia Cancer in Rural Areas of Linzhou

  • Sun, Chang-Qing;Chang, Yu-Bo;Cui, Ling-Ling;Chen, Jia-Jun;Sun, Nan;Zhang, Wei-Jie;Jia, Xiao-Can;Tian, Yuan;Dai, Li-Ping
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.2897-2901
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    • 2013
  • Gastric cancer is the second most common cause of cancer-related deaths in the world. Although certain dietary factors and lifestyles have been suggested to be associated with gastric carcinogenesis, there have been few investigations focusing on rural areas. A case-control study was therefore carried out to investigate the risk factors of gastric cardia cancer (GCC) in rural areas of Linzhou. A total of 470 newly diagnosed cases of GCC and 470 healthy controls were included. Face-to-face interviews were conducted, using a uniform questionnaire containing questions on demographics, per capita income, living habits, dietary habits and family history of tumors. The relationship between putative risk factors and GCC was assessed by odds ratios (OR) and their 95% confidence intervals (95%CI) derived from conditional logistic regression model by the COXREG command using SPSS 12.00. Multivariate logistic regression analysis was used to evaluate simultaneously the effects of multiple factors and other potential confounding factors. Multivariate logistic analysis showed that smoking (OR=1.939, 95%CI:1.097-3.426), alcohol drinking (OR=2.360, 95%CI: 1.292-4.311), hot food consumption (OR=2.034, 95%CI: 1.507-2.745), fast eating (OR=1.616, 95%CI: 1.171-2.230), mouldy food (OR=4.564, 95%CI: 2.682-7.767), leftover food (OR=1.881. 95%CI: 1.324-2.671), and family history of tumor (OR=2.831, 95%CI: 1.588-5.050) were risk factors for GCC. High per capita income (OR=0.709, 95%CI: 0.533-0.942), high education level (OR=0.354, 95%CI: 0.163-0.765), consumption of fresh fruits (OR=0.186, 95%CI: 0.111-0.311) and vegetables (OR=0.243, 95%CI: 0.142-0.415), and high BMI (OR=0.367, 95%CI: 0.242-0.557) were protective factors for GCC. Our data indicate that unhealthy lifestyle and dietary habits might be important contributors to GCC in this population.

Gamma Knife Radiosurgery for Brain Metastases from Breast Cancer

  • Jo, Kyung Il;Im, Young-Hyuck;Kong, Doo Sik;Seol, Ho Jun;Nam, Do-Hyun;Lee, Jung-Il
    • Journal of Korean Neurosurgical Society
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    • v.54 no.5
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    • pp.399-404
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    • 2013
  • Objective : The authors conducted a retrospective cohort study to determine prognostic factors and treatment outcomes of brain metastases (BM) from breast cancer (BC) after Gamma Knife radiosurgery (GKS). Methods : Pathologic and clinical features, and outcomes were analyzed in a cohort of 62 patients with BM from BC treated by GKS. The Kaplan- Meier method, the log-rank test, and Cox's proportional hazards model were used to assess prognostic factors. Results : Median survival after GKS was 73.0 weeks (95% confidence interval, 46.0-100.1). HER2+ [hazard ratio (HR) 0.441; p=0.045], Karnofsky performance scale (KPS) ${\geq}70$ (RR 0.416; p=0.050) and systemic chemotherapy after GKS (RR 0.282; p=0.001) were found to be a favorable prognostic factor of overall survival. Actuarial local control (LC) rate were $89.5{\pm}4.5%$ and $70.5{\pm}6.9%$ at 6 and 12 months after GKS, respectively. No prognostic factors were found to affect LC rate. Uni- and multivariate analysis revealed that the distant control (DC) rate was higher in patients with; a small number (${\leq}3$) of metastasis (HR 0.300; p=0.045), no known extracranial metastasis (p=0.013, log-rank test), or the HER2+ subtype (HR 0.267; p=0.027). Additional whole brain radiation therapy and metastasis volume were not found to be significantly associated with LC, DC, or overall survival. Conclusion : The treatment outcomes of patients with newly diagnosed BM from BC treated with GKS could be affected primarily by intrinsic subtype, KPS, and systemic chemotherapy. Therapeutic strategy and prognosis scoring system should be individualized based on considerations of intrinsic subtype in addition to traditionally known parameters related to stereotactic radiosurgery.

Association between Glycemic Index, Glycemic Load, Dietary Carbohydrates and Diabetes from Korean National Health and Nutrition Examination Survey 2005 (2005 국민건강영양조사 자료 분석을 통한 한국 성인 남녀의 식이 중 Glycemic Index, Glycemic Load 및 탄수화물 섭취 수준과 당뇨 발병과의 관련성 연구)

  • Kim, Eun-Kyung;Lee, Jung-Sug;Hong, Hee-Ok;Yu, Choon-Hie
    • Journal of Nutrition and Health
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    • v.42 no.7
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    • pp.622-630
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    • 2009
  • The purpose of this study was to establish an association between glycemic index (GI), glycemic load (GL), dietary carbohydrates and diabetes with the context of the current population dietary practice in Korea. The subjects of 3,389 adults (male 1,430, female 1,959) were divided into normal (serum fasting glucose < 100 mg/dL), impaired glucose tolerance (100 ${\leq}$ serum fasting glucose < 126 mg/dL), diabetes (serum fasting glucose > 126 mg/dL) by serum fasting glucose. Anthropometric and hematologic factors, and nutrient intakes, dietary glycemic index (DGI), dietary glycemic load (DGL) were assessed. Multiple logistic regression model was used to determine the odds ratios (ORs) and 95% confidence intervals for relationship of DGI, DGL, carbohydrates intakes, and diabetes. DGI and DGL were not significantly correlated with impaired glucose tolerance and diabetes. However, the risk of impaired glucose tolerance and diabetes showed a tendency to increase as increase of DGI after multivariate adjustment (age, education, income, region area, diabetes family history, smoking, drinking, exercise, energy intake) in male. The risk of impaired glucose tolerance and diabetes showed a tendency to increase in the DGI 71.1-74.8 after multivariate adjustment in female. DGL was inversely related to impaired glucose tolerance and diabetes in male. In female, however, DGL was positively related to impaired glucose tolerance and diabetes. In particular, the risk of diabetes increased positively in level of DGL 260.5, and remained after multivariate adjustment (Q5 vs Q1:2.38, 0.87-6.48). When percent energy intakes from carbohydrates were more than 70%, the risk of impaired glucose tolerance and diabetes increased in both male and female. In particular, when percent energy intakes from carbohydrates were more than 69.9%, the risk of diabetes increased positively in male (Q4 vs Q1:2.34, 1.16-4.17). In conclusion, above 70% energy intakes from carbohydrates appeared to be a risk factor of diabetes. It seemed that the meal with high GI and GL value must be avoided it. And also, the macronutrients of the meal must be properly balanced. In particular, it may be said that it is a preventive way for treatment of the diabetes to avoid eating carbohydrates of much quantity.

Meta-analysis of Associations between ATM Asp1853Asn and TP53 Arg72Pro Polymorphisms and Adverse Effects of Cancer Radiotherapy

  • Su, Meng;Yin, Zhi-Hua;Wu, Wei;Li, Xue-Lian;Zhou, Bao-Sen
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.24
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    • pp.10675-10681
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    • 2015
  • Background: The ataxia telangiectasia mutated (ATM) protein and p53 play key roles in sensing and repairing radiation-induced DNA double strand breaks (DSBs). Accumulating epidemiological evidence indicates that functional genetic variants in ATM and TP53 genes may have an impact on the risk of radiotherapy-induced side effects. Here we performed a meta-analysis to investigate the potential interaction between ATM Asp1853Asn and TP53 polymorphisms and risk of radiotherapy-induced adverse effects quantitatively. Materials and Methods: Relevant articles were retrieved from PubMed, ISI Web of Science and the China National Knowledge Infrastructure (CNKI) databases. Eligible studies were selected according to specific inclusion and exclusion criteria. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled to estimate the association between ATM Asp1853Asn and TP53 Arg72Pro polymorphisms and risk of radiotherapy adverse effects. All analyses were performed using the Stata software. Results: A total of twenty articles were included in the present analysis. In the overall analysis, no significant associations between ATM Asp1853Asn and TP53 Arg72Pro polymorphisms and the risk of radiotherapy adverse effects were found. We conducted subgroup analysis stratified by type of cancer, region and time of appearance of side effects subsequently. No significant association between ATM Asp1853Asn and risk of radiotherapy adverse effects was found in any subgroup analysis. For TP53 Arg72Pro, variant C allele was associated with decreased radiotherapy adverse effects risk among Asian cancer patients in the stratified analysis by region (OR=0.71, 95%CI: 0.54-0.93, p=0.012). No significant results were found in the subgroup analysis of tumor type and time of appearance of side effects. Conclusions: The TP53 Arg72Pro C allele might be a protective factor of radiotherapy-induced adverse effects among cancer patients from Asia. Further studies that take into consideration treatment-related factors and patient lifestyle including environmental exposures are warranted.

Association of Polymorphisms in Stress-Related TNFα and NPY Genes with the Metabolic Syndrome in Han and Hui Ethnic Groups

  • Bu, De-Yun;Ji, Wen-Wu;Bai, Dan;Zhou, Jian;Li, Hai-Xia;Yang, Hui-Fang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.14
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    • pp.5895-5900
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    • 2014
  • Background: Metabolic syndrome (MS) is a cluster of complicated disorders caused by the interactive influencing factors of heredity and environment, which predisposes to many cnacers. Results from epidemic research indicate that stress is tightly related to the pathogenesis of MS and neoplasia. This paper aims to investigate the association between psychological stress and MS with respect to the tumor necrosis factor alpha (TNF${\alpha}$) and neuropeptide Y (NPY) genes in the Han and Hui ethnic groups. Methods: All subjects for this case-control study matched strict enrollment criteria (nationality, gender and age) and lived in the city of Wu Zhong of Ningxia Province in China. The enrolled group contained 102 matched pairs of Hui ethnic individuals and 98 matched pairs of Han ethnic individuals. Enrolled subjects completed the general Symptom Checklist-90 (SCL-90). The TNF${\alpha}$-308G/A variant and NPYrs16147 polymorphism were detected in case (81 males, 119 females) and control (81 males, 119 females) groups by polymerase chain reaction (PCR) amplification. Results: Nine factors of the SCL-90 were found to be statistically different (p<0.05) between case and control groups. The homozygous mutant genotype (AA) and the mutant allele (A) of the TNF${\alpha}$-308G/A gene were less frequently observed in the control population compared to the case group. The odds ratio (95% confidence interval) in "Allele" for MS was 2.28 (1.47-3.53), p=0.0001, while "OR" was 1.11 (0.83-1.47), p=0.15, for the NPYrs16147 gene polymorphism. Conclusions: Psychological stress has been positively associated with MS. A previous study from our group suggested there were differences in the level of psychological stress between Hui and Han ethnic groups. Furthermore, we found that the stress-related TNF${\alpha}$ gene was associated with MS for both Han and Hui ethnic groups. In contrast, NPY may be a possible contributor to MS and associated cancer for the Han ethnic group.