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Genetic Variants of NBS1 Predict Clinical Outcome of Platinum-based Chemotherapy in Advanced Non-small Cell Lung Cancer in Chinese

  • Xu, Jia-Li;Hu, Ling-Min;Huang, Ming-De;Zhao, Wan;Yin, Yong-Mei;Hu, Zhi-Bin;Ma, Hong-Xia;Shen, Hong-Bing;Shu, Yong-Qian
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.3
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    • pp.851-856
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    • 2012
  • Objective: NBS1 plays a key role in the repair of DNA double-strand break (DSB). We conducted this study to investigate the effect of two critical polymorphisms (rs1805794 and rs13312840) in NBS1 on treatment response and prognosis of advanced non-small cell lung cancer (NSCLC) patients with platinum-based chemotherapy. Methods: Using TaqMan methods, we genotyped the two polymorphisms in 147 NSCLC patients. Odds ratios (ORs) and their 95% confidential intervals (CIs) were calculated as a measure of difference in the response rate of platinum-based chemotherapy using logistic regression analysis. The Kaplan-Meier and log-rank tests were used to assess the differences in progression-free survival (PFS) and overall survival (OS). Cox proportional hazards model was applied to assess the hazard ratios (HRs) for PFS and OS. Results: Neither of the two polymorphisms was significantly associated with treatment response of platinum-based chemotherapy. However, patients carrying the rs1805794 CC variant genotype had a significantly improved PFS compared to those with GG genotype (16.0 vs. 8.0 months, P = 0.040). Multivariable cox regression analysis further showed that rs1805974 was a significantly favorable prognostic factor for PFS [CC/CG vs. GG: Adjusted HR = 0.62, 95% CI: 0.39-0.99; CC vs. CG/GG: Adjusted HR = 0.56, 95% CI: 0.32-0.97). Similarly, rs13312840 with a small sample size also showed a significant association with PFS (CC vs. CT/TT: Adjusted HR = 25.62, 95% CI: 1.53-428.39). Conclusions: Our findings suggest that NBS1 polymorphisms may be genetic biomarkers for NSCLC prognosis especially PFS with platinum-based chemotherapy in the Chinese population.

P53 Arg72Pro Polymorphism and Bladder Cancer Risk - Meta-analysis Evidence for a Link in Asians but not Caucasians

  • Xu, Ting;Xu, Zi-Cheng;Zou, Qin;Yu, Bin;Huang, Xin-En
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.2349-2354
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    • 2012
  • Objective: Individual studies of the associations between P53 codon 72 polymorphism (rs1042522) and bladder cancer susceptibility have shown inconclusive results. To derive a more precise estimation of the relationship, we performed this systemic review and meta-analysis based on 15 publications. Methods: We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Results: We found that there was no association between P53 codon 72 polymorphism and bladder cancer risk in the comparisons of Pro/Pro vs Arg/Arg; Pro/Arg vs. Arg/Arg; Pro/Pro plus Pro/Arg vs. Arg/Arg; Arg/Arg vs. Pro/Arg plus Arg/Arg (OR=1.06 95%CI 0.81-1.39; OR=1.06 95%CI 0.83-1.36; OR=0.98 95%CI 0.78-1.23; OR=1.06 95%CI 0.84-1.32). However, a significantly increased risk of bladder cancer was found among Asians in the homozygote comparison (Pro/Pro vs. Arg/Arg, OR=1.36 95%CI 1.05-1.75, P=0.790 for heterogeneity) and the dominant model (Arg/Pro plus Pro/Pro vs. Arg/Arg, OR=1.26 95%CI 1.05-1.52, P=0.564 for heterogeneity). In contrast, no evidence of an association between bladder cancer risk and P53 genotype was observed among Caucasian population in any genetic model. When stratifying for the stage of bladder, no statistical association were found (Pro/Pro vs. Arg/Arg, OR=0.45 95%CI 0.17-1.21; Pro/Arg vs. Arg/Arg, OR=0.60 95%CI 0.28-1.27; Dominant model, OR=0.56 95%CI 0.26-1.20; Recessive model, OR=0.62 95%CI0.35-1.08) between P53 codon 72 polymorphism and bladder cancer in all comparisons. Conclusions: Despite the limitations, the results of the present meta-analysis suggest that, in the P53 codon 72, Pro/Pro type and dominant mode might increase the susceptibility to bladder cancer in Asians; and there are no association between genotype distribution and the stage of bladder cancer.

Factors Associated with the Continuous Abstinence Rate from Smoking on Smoking Cessation Program over 6 Months in College Students of Daejeon, Korea (대전 지역 대학생의 6개월 금연 성공 관련 요인)

  • Seo, Eun-Seon;Kim, Chul-Woung;Lee, Seung Eun;Im, Hyo-Bin;Lee, Sang-Yi;Kang, Jung-Hee
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.21 no.1
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    • pp.247-257
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    • 2020
  • Despite the various smoking cessation programs that are available for college students, students have lower rates of quitting smoking than do other age groups. This study identifies the variables associated with continuous abstinence from smoking among college students. This study used the data from the National Tobacco Control Center and 781 college students who participated in the program conducted by the Daejeon Tobacco Control Center from June, 2015 to December, 2016. The results showed that the expiration CO level and the frequency of attending smoking cessation counseling were the significant variables related to the continuous abstinence rate at 4, 12, and 24 weeks. Students who had a low expiration CO level (?10 ppm) had a higher abstinence rate than did the students who had a high expiration CO level (≥10ppm), and the OR was 2.53 at 4-week, 2.33 at 12-week, and 2.13 at 24-week. The ORs for the 4-week, 12-week, and 24-week abstinence rates with one additional counseling session were 12.39, 13.13, and 12.21, respectively. This study suggests the need to increase the number of smoking cessation counseling sessions for effective smoking cessation intervention among college students.

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.

N-Acetyltransferase 2 Gene Polymorphisms are Associated with Susceptibility to Cancer: a Meta-analysis

  • Tian, Fang-Shuo;Shen, Li;Ren, Yang-Wu;Zhang, Yue;Yin, Zhi-Hua;Zhou, Bao-Sen
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.14
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    • pp.5621-5626
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    • 2014
  • N-acetyltransferase 2 (NAT2) is a polymorphic enzyme that plays an important role in the metabolism of various potential carcinogens. In recent years, a number of studies have been carried out to investigate the relationship between the rs1799930 and rs1799931 polymorphism in NAT2 and cancer risk in multiple populations for different types of cancer. However, the results were not consistent. Therefore, we performed a meta-analysis to further explore the relationship between NAT2 polymorphism and the risk of cancer. A total of 21 studies involving 15, 450 subjects for rs1799930 and 13, 011 subjects for rs1799931 were included in this meta-analysis. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess strength of associations. We also evaluated the publication bias and performed a sensitivity analysis. Overall, our results showed an apparent significant association between the NAT2 rs1799930 polymorphism and cancer susceptibility in Asians (GA vs. GG: OR=1.22, 95% CI=1.03-1.45; dominant model: OR=1.22, 95% CI=1.03-1.43) and population-based controls (GA vs. GG: OR=1.10, 95% CI=1.01-1.19; dominant model: OR=1.09, 95% CI=1.01-1.18). In contrast, a significant association was observed between the NAT2 rs1799931 G>A polymorphism and decreased cancer susceptibility in overall meta-analysis (AA vs. GG: OR=0.55, 95% CI=0.33-0.93; GA vs. GG: OR=1.00, 95% CI=0.88-1.14; dominant model: OR=0.97, 95% CI=0.86-1.10; recessive model: OR=0.56, 95% CI=0.34-0.94) and the Asian group (AA vs. GG: OR=0.50, 95% CI=0.26-0.94; recessive model, OR=0.50, 95% CI=0.27-0.94). We found that the NAT2 rs1799930 may be a risk factor, while the NAT2 rs1799931 polymorphism is associated with a decreased risk of cancer and is likely a protective factor against cancer development.

Contribution of the MLH1 -93G>A Promoter Polymorphism in Modulating Susceptibility Risk in Malaysian Colorectal Cancer Patients

  • Nizam, Zahary Mohd;Abdul Aziz, Ahmad Aizat;Kaur, Gurjeet;Abu Hassan, Muhammad Radzi;Mohd Sidek, Ahmad Shanwani;Lee, Yeong Yeh;Mazuwin, Maya;Ankathil, Ravindran
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.2
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    • pp.619-624
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    • 2013
  • Background: Colorectal cancer (CRC) exists in a more common sporadic form and less common hereditary forms, associated with the Lynch syndrome, familial adenomatous polyposis (FAP) and other rare syndromes. Sporadic CRC is believed to arise as a result of close interaction between environmental factors, including dietary and lifestyle habits, and genetic predisposition factors. In contrast, hereditary forms such as those related to the Lynch syndrome result from inheritance of germline mutations of mismatch repair (MMR) genes. However, in certain cases, the influence of low penetrance alleles in familial colorectal cancer susceptibility is also undeniable. Aim: To investigate the genotype frequencies of MLH1 promoter polymorphism -93G>A and to determine whether it could play any role in modulating familial and sporadic CRC susceptibility risk. Methods: A case-control study comprising of 104 histopathologically confirmed CRC patients as cases (52 sporadic CRC and 52 Lynch syndrome patients) and 104 normal healthy individuals as controls was undertaken. DNA was extracted from peripheral blood and the polymorphism was genotyped employing PCR-RFLP methods. The genotypes were categorized into homozygous wild type, heterozygous and homozygous variants. The risk association between these polymorphisms and CRC susceptibility risk was calculated using binary logistic regression analysis and deriving odds ratios (ORs). Results: When risk association was investigated for all CRC patients as a single group, the heterozygous (G/A) genotype showed a significantly higher risk for CRC susceptibility with an OR of 2.273, (95%CI: 1.133-4.558 and p-value=0.021). When analyzed specifically for the 2 types of CRC, the heterozygous (G/A) genotype showed significantly higher risk for sporadic CRC susceptibility with and OR of 3.714, (95%CI: 1.416-9.740 and p-value=0.008). Despite high OR value was observed for Lynch syndrome (OR: 1.600, 95%CI: 0.715-3.581), the risk was not statistically significant (P=0.253). Conclusion: Our results suggest an influence of MLH1 promoter polymorphism -93G>A in modulating susceptibility risk in Malaysian CRC patients, especially those with sporadic disease.

Osteoporosis Prevalence of Radius and Tibia and Related Factors Using Multiple Bone Sites Quantitative Ultrasound Measurement of the Korean Health and Genome Study Cohort Women (지역사회 코호트 여성의 요골과 경골에서의 골다공증 유병률과 관련 요인 분석)

  • Park Seon-Joo;Abn Younjhin;Min Hae Sook;Oh Kyoung Soo;Park Chan;Cho Nam Han;Kim Kuchan
    • Korean Journal of Community Nutrition
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    • v.10 no.4
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    • pp.536-545
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    • 2005
  • This study was conducted to investigate osteopenia and osteoporosis prevalence of radius and tibia using Quantitative Ultrasound (QUS) and to identify affecting factors of osteoporosis. A total of 4,340 women aged 40 - 69 years, living in Ansung (rural) and Ansan (mid-sized) area, and free of illnesses affecting bone metabolism participated in the community-based cohort study. Among them 4,059 subjects measured radius bone density and 4,089 measured tibia. The T-score threshold, defined as < -1.0 and $\le$-2.5, was used to identify subjects with osteopenia and osteoporosis by WHO criteria. The crude prevalence of osteoporosis in radius and tibia was $8.4\%$ and $23.3\%$ respectively; after adjustment for age, it changed $6.3\%$ and $18.8\%$. In simple logistic regression analysis, the prevalence of osteoporosis increased by aging, non-marital status, low education, low income. Otherwise, high intakes of Ca/P, thiamin, riboflavin, vitamin B6, and vitamin E were decreased osteoporosis prevalence. Compared to the normal BMI (body mass index) group 08.5 $\le$ BMI < 23), the odds ratio (ORs) of the low BMI group (BMI < 18.5), and high BMI groups (BMl25-30, BMI $\ge$ 30) were significantly increased. The OR of osteoporosis decreased across increasing quartiles of intakes of Ca, P and Ca/P. Therefore, maintaining normal BMI and increasing Ca intake and Ca/P ratio may have a beneficial effect on bone health of Korean women.

Association of Current and Past Smoking with Metabolic Syndrome in Men (성인남성에서 현재 및 과거 흡연과 대사증후군의 관련성)

  • Hong, A-Rum;Lee, Kang-Sook;Lee, Seon-Young;Yu, Jae-Hee
    • Journal of Preventive Medicine and Public Health
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    • v.42 no.3
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    • pp.160-164
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    • 2009
  • Objectives : The objective of this study was to determine the relationship between past smoking and the risk factors for metabolic syndrome. Methods : From January 2007 to December 2007, a total of 3,916 over thirty years old male health screen examinees were divided into the nonsmoking, smoking, ex-smoking groups. The diagnosis of metabolic syndrome was based on the criteria of the NCEP ATP III(Executive Summary of The Third Report of The National Cholesterol Education Program). Metabolic syndrome was defined as the presence of three or more of the following: a blood pressure $\geq$ 130/85 mmHg, a fasting glucose level $\geq$ 110 mg/dL, a HDL-C (High Density Lipoprotein Cholesterol) level < 40 mg/dL, a triglyceride level $\geq$ 150 mg/dL and, a waist circumference men $\geq$ 102 cm, but a waist to hip ratio > 0.90 was used as a surrogate for the waist circumference. Results : After adjustment for age, alcohol consumption and, exercise in the smokers, for the ex-smokers compared with the nonsmokers, the odds ratio (OR) of a lower HDL cholesterol level (<40 mg/dL) was 1.29 (95% CI=1.03-1.61) in the smokers, the ORs of a higher triglyceride level were 1.35 (95% CI=1.09-1.66) in the ex-smokers and, 2.12 (95% CI=1.75-2.57) in the smokers, and the OR of a waist to hip ratio was 1.25 (95% CI=1.03-1.52) in the ex-smokers. When there were over three components of metabolic syndrome in the ex-smokers and smokers as compared with the nonsmokers, the odds ratio against the risk of metabolic syndrome were 2.39 (95% CI=1.00-6.63) and 2.37 (95% CI=1.02-6.46), respectively. Conclusions : The present study suggested that there is an association of smoking with metabolic syndrome in men.

A Study on Relationship to Risk Factors according to Menopausal Status in Breast Cancer (유방암 환자에 있어서 폐경상태에 따른 위험인자의 상관성 연구)

  • Yoon, Han-Sik
    • Journal of radiological science and technology
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    • v.23 no.1
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    • pp.49-54
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    • 2000
  • It is important to identify modifiable risk factors for breast cancer, because the breast cancer is one of the major causs of mortality among women. Some reported that obesity is a risk factor for breast cancer, but the results are not constant. Many risk factors are related to the duration of estrogenic stimulation of the breast. In general, early menarche and late menopause are positive risk factors. Human breast cancer has different characteristics according to the status of menopause(premenopause and postmenopause). In premenopausal women, about 60% of circulating estrogen is from the ovaries in the form of estradiol, and the remaining 40% is estrogen formed primarily in the adipose(fat) tissue via aromatization of androstenedion from the adrenal glands. After menopause this adipose cell production of estrone is the main source of estrogens and the level of estrone is maintained approximately at premenopausal levels. This study was undertaken to determine the role of body size and body mass index by status of menopause in development of breast cancer using retrospective case/control study. From March 1991 to February 1997 at the Wonkwang University Hospital, the breast cancer cases(n=72) and controls(n=86) were selected. By statistical analysis method, regression analysis, paired T-test and multiple logistic regression were done to estimate the influenced factors same as height, weight, BMI, age at menarche and age at menopause. The following results were obtained : 1. In premenopausal women, age at menarche was showed comparatively high correlation coefficients and BMI was described prominently highly in postmenopause. 2. At the results of multiple regression analysis, age at monarch, BMI and weight were showed as significant variables. In this method, critical factor ($R^2$) was 0.054. 3. Paired samples T-test was undertaken to test mean difference between two groups of cases and controls. The result of test performance showed a significant difference. 4. In comparison with women whose weight less than 50 kg, the ORs for the upper 5th group was 1.82(95% confidence interval). The heaviest women had a higher risk(OR=1.14, 95% confidence interval $1.12{\sim}1.31$, p=0.005). Higher body mass index was significantly associated with increased risk of premenopausal breast cancer (OR=1.01, 95% confidence interval $1.08{\sim}l.18$, p=0.05).

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