Browsing by Subject "Asian Continental Ancestry Group"
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Item Open Access A Functional Polymorphism (rs2494752) in the AKT1 Promoter Region and Gastric Adenocarcinoma Risk in an Eastern Chinese Population.(Scientific reports, 2016-01-28) Wang, Meng-Yun; He, Jing; Zhu, Mei-Ling; Teng, Xiao-Yan; Li, Qiao-Xin; Sun, Meng-Hong; Wang, Xiao-Feng; Yang, Ya-Jun; Wang, Jiu-Cun; Jin, Li; Wang, Ya-Nong; Wei, Qing-YiAKT is an important signal transduction protein that plays a crucial role in cancer development. Therefore, we evaluated associations between single nucleotide polymorphisms (SNPs) in the AKT promoter region and gastric cancer (GCa) risk in a case-control study of 1,110 GCa patients and 1,114 matched cancer-free controls. We genotyped five SNPs (AKT1 rs2494750G >C, AKT1 rs2494752A >G, AKT1 rs10138227C >T, AKT2 rs7254617G>A and AKT2 rs2304186G >T) located in the 5' upstream regulatory, first intron or promoter regions. In the logistic regression analysis, a significantly elevated GCa risk was associated with the rs2494752 AG/GG variant genotypes (adjusted odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.02-1.42) under a dominant genetic model, and this risk was more evident in subgroups of ever drinkers. The luciferase reporter assay showed that the rs2494752 G allele significantly increased luciferase activity. Our results suggest that the potentially functional AKT1 rs2494752 SNP may affect GCa susceptibility, likely by modulating the AKT1 promoter transcriptional activity. Larger, independent studies are warranted to validate our findings.Item Open Access A genetic variant in the APE1/Ref-1 gene promoter -141T/G may modulate risk of glioblastoma in a Chinese Han population.(BMC cancer, 2011-01) Zhou, Keke; Hu, Dezhi; Lu, Juan; Fan, Weiwei; Liu, Hongliang; Chen, Hongyan; Chen, Gong; Wei, Qingyi; Du, Guhong; Mao, Ying; Lu, Daru; Zhou, LiangfuBACKGROUND: The human apurinic/apyrimidinic endonuclease 1/Redox effector factor-1 (APE1/Ref-1) is implicated in tumor development and progression. Recently, the APE1/Ref-1 promoter -141T/G variant (rs1760944) has been reported to be associated with lung cancer risk. Given the importance of APE1/Ref-1 in both DNA repair and redox activity, we speculate that the -141T/G polymorphism may confer individual susceptibility to gliomas or its subtypes. METHODS: The APE1/Ref-1 -141T/G polymorphism was analyzed in a case-control study including 766 glioma patients (among them 241 glioblastoma, 284 astrocytomas except for glioblastoma and 241 other gliomas) and 824 cancer-free controls from eastern China. Genotyping was performed with Sequenom MassARRAY iPLEX platform by use of allele-specific MALDI-TOF mass spectrometry assay. We estimated odds ratios (ORs) and 95% confidence intervals (95% CIs) using unconditional logistic regression. A test of trend was calculated using the genotype as an ordinal variable in the regression model. For each statistically significant association identified, we estimated the false positive reporting probability (FPRP). FPRP values less than 0.2 were consider to indicate robust associations. RESULTS: The significant association between the APE1/Ref-1 promoter -141T/G polymorphism and glioma risk was not observed. However, the stratified analysis by histology revealed the variant allele G significantly decreased glioblastoma risk (OR = 0.80, 95% CI = 0.65-0.98, P = 0.032). Individuals with the homozygous -141GG genotype exhibited 46% reduced risk of glioblastoma (adjusted OR = 0.54, 95% CI 0.34-0.87, P = 0.012), compared with the TT homozygote. This result remained robust given the prior probabilities of 25% (FPRP = 0.052) and 10% (FPRP = 0.140), but not with a prior probability of 1% (FPRP = 0.643). The P-associated with the trend test was 0.014. CONCLUSIONS: Our results suggest that a specific genetic variant located in the APE1/Ref-1 promoter may modulate risk of glioblastoma, but not for other histological gliomas. Larger studies with more APE1 polymorphisms are required to validate these preliminary findings.Item Open Access A genome-wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese.(PLoS Genet, 2010-02-19) Tsai, Fuu-Jen; Yang, Chi-Fan; Chen, Ching-Chu; Chuang, Lee-Ming; Lu, Chieh-Hsiang; Chang, Chwen-Tzuei; Wang, Tzu-Yuan; Chen, Rong-Hsing; Shiu, Chiung-Fang; Liu, Yi-Min; Chang, Chih-Chun; Chen, Pei; Chen, Chien-Hsiun; Fann, Cathy SJ; Chen, Yuan-Tsong; Wu, Jer-YuarnTo investigate the underlying mechanisms of T2D pathogenesis, we looked for diabetes susceptibility genes that increase the risk of type 2 diabetes (T2D) in a Han Chinese population. A two-stage genome-wide association (GWA) study was conducted, in which 995 patients and 894 controls were genotyped using the Illumina HumanHap550-Duo BeadChip for the first genome scan stage. This was further replicated in 1,803 patients and 1,473 controls in stage 2. We found two loci not previously associated with diabetes susceptibility in and around the genes protein tyrosine phosphatase receptor type D (PTPRD) (P = 8.54x10(-10); odds ratio [OR] = 1.57; 95% confidence interval [CI] = 1.36-1.82), and serine racemase (SRR) (P = 3.06x10(-9); OR = 1.28; 95% CI = 1.18-1.39). We also confirmed that variants in KCNQ1 were associated with T2D risk, with the strongest signal at rs2237895 (P = 9.65x10(-10); OR = 1.29, 95% CI = 1.19-1.40). By identifying two novel genetic susceptibility loci in a Han Chinese population and confirming the involvement of KCNQ1, which was previously reported to be associated with T2D in Japanese and European descent populations, our results may lead to a better understanding of differences in the molecular pathogenesis of T2D among various populations.Item Open Access A pri-miR-218 variant and risk of cervical carcinoma in Chinese women.(BMC cancer, 2013-01-15) Shi, Ting-Yan; Chen, Xiao-Jun; Zhu, Mei-Ling; Wang, Meng-Yun; He, Jing; Yu, Ke-Da; Shao, Zhi-Ming; Sun, Meng-Hong; Zhou, Xiao-Yan; Cheng, Xi; Wu, Xiaohua; Wei, QingyiBACKGROUND: MicroRNA (miRNA)-related single nucleotide polymorphisms (SNPs) may compromise miRNA binding affinity and modify mRNA expression levels of the target genes, thus leading to cancer susceptibility. However, few studies have investigated roles of miRNA-related SNPs in the etiology of cervical carcinoma. METHODS: In this case-control study of 1,584 cervical cancer cases and 1,394 cancer-free female controls, we investigated associations between two miR-218-related SNPs involved in the LAMB3-miR-218 pathway and the risk of cervical carcinoma in Eastern Chinese women. RESULTS: We found that the pri-miR-218 rs11134527 variant GG genotype was significantly associated with a decreased risk of cervical carcinoma compared with AA/AG genotypes (adjusted OR=0.77, 95% CI=0.63-0.95, P=0.015). However, this association was not observed for the miR-218 binding site SNP (rs2566) on LAMB3. Using the multifactor dimensionality reduction analysis, we observed some evidence of interactions of these two SNPs with other risk factors, especially age at primiparity and menopausal status, in the risk of cervical carcinoma. CONCLUSIONS: The pri-miR-218 rs11134527 SNP was significantly associated with the risk of cervical carcinoma in Eastern Chinese women. Larger, independent studies are warranted to validate our findings.Item Open Access A recessive variant of XRCC4 predisposes to non- BRCA1/2 breast cancer in chinese women and impairs the DNA damage response via dysregulated nuclear localization.(Oncotarget, 2014-12) He, Min; Hu, Xin; Chen, Li; Cao, A-Yong; Yu, Ke-Da; Shi, Ting-Yan; Kuang, Xia-Ying; Shi, Wen-Biao; Ling, Hong; Li, Shan; Qiao, Feng; Yao, Ling; Wei, Qingyi; Di, Gen-Hong; Shao, Zhi-MingXRCC4 plays a crucial role in the non-homologous end joining pathway that maintains genome stability. In this two-stage case-control study with 1,764 non-BRCA1/2 breast cancer patients and 1,623 cancer-free controls, we investigated the contribution of genetic variants of XRCC4 to breast cancer susceptibility in Chinese women. We identified a recessive missense variant, rs3734091 (c.739G>T, p.Ala247Ser), of XRCC4 that was significantly associated with an increased risk of breast cancer (odds ratio [OR] = 3.92, P = 0.007), particularly with the risk of developing triple-negative breast cancer (OR = 18.65, P < 0.0001). This p.Ala247Ser variant disturbed the nuclear localization of XRCC4 in cells homozygous for the rs3734091-T allele but not in heterozygous cells at both the cellular and tissue levels. In heterozygous cells, wild-type XRCC4 facilitated the nuclear localization of the XRCC4A247S mutant, thus compensating for the impaired localization of XRCC4A247S. This provided a biological mechanism by which rs3734091 conferred an increased susceptibility to non-BRCA1/2 breast cancer exclusively under a recessive model. Further functional analyses revealed that p.Ala247Ser impaired the DNA damage repair capacity and ultimately perturbed genomic stability. Taken together, our findings document the role of XRCC4 in non-BRCA1/2 breast cancer predisposition and reveal its underlying biological mechanism of action.Item Open Access Association between p21 Ser31Arg polymorphism and cancer risk: a meta-analysis.(Chinese journal of cancer, 2011-04) Ma, Hongxia; Zhou, Ziyuan; Wei, Sheng; Wei, QingyiP21 (CDKN1A), a key cell cycle regulatory protein that governs cell cycle progression from G1 to S phase, can regulate cell proliferation, growth arrest, and apoptosis. The Ser31Arg polymorphism is located in the highly conserved region of p21 and may encode functionally distinct proteins. Although many epidemiological studies have been conducted to evaluate the association between the p21 Ser31Arg polymorphism and cancer risk, the findings remain conflicting. This meta-analysis with 33 077 cases and 45 013 controls from 44 published case-control studies showed that the variant homozygous 31Arg/Arg genotype was associated with an increased risk of numerous types of cancers in a random-effect model (homozygote comparison: OR = 1.17, 95% CI = 0.99 to 1.37, P = 0.0002 for the heterogeneity test; recessive model comparison: OR = 1.16, 95% CI = 1.01 to 1.33, P = 0.0001 for the heterogeneity test). Stratified analysis revealed that increased cancer risk associated with the 31Arg/Arg genotype remained significant in subgroups of colorectal cancer, estrogen-related cancer, Caucasians, population-based studies, studies with matching information or a larger sample size. Heterogeneity analysis showed that tumor type contributed to substantial between-study heterogeneity (recessive model comparison: Χ(2) = 21.83, df = 7, P = 0.003). The results from this large-sample sized meta-analysis suggest that the p21 31Arg/Arg genotype may serve as a potential marker for increased cancer risk.Item Open Access Associations of genotypes and haplotypes of IL-17 with risk of gastric cancer in an eastern Chinese population.(Oncotarget, 2016-12) Zhou, Fei; Qiu, Li-Xin; Cheng, Lei; Wang, Meng-Yun; Li, Jin; Sun, Meng-Hong; Yang, Ya-Jun; Wang, Jiu-Cun; Jin, Li; Wang, Ya-Nong; Wei, Qing-YiInterleukin-17 plays a crucial role in inflammation-related carcinogenesis. We hypothesize that genetic variants in IL-17 are associated with gastric cancer (GCa) risk, and we genotyped five potentially functional single nucleotide polymorphisms (SNPs) (rs1974226 G > A, rs2275913 A > G, rs3819024 A > G, rs4711998 A > G, and rs8193036 C > T) of IL-17 in 1121 GCa patients and 1216 cancer-free controls in an eastern Chinese population. Logistic regression analysis was used to calculate odds ratios (OR) and 95% confidence intervals (CI). Meta-analysis and genotype-mRNA expression correlation were performed to further validate positive associations. We found that an increased GCa risk was independently associated with rs1974226 (adjusted OR = 2.60, 95% CI = 1.27-5.32 for AA vs. GG + GA) and rs2275913 (adjusted OR = 1.33, 95% CI = 1.03-1.72 for GA + AA vs. GG), while a decreased GCa risk was independently associated with rs3819024 (adjusted OR = 0.72, 95% CI = 0.54-0.96 for GG vs. AA + AG). Additional meta-analyses confirmed the observed risk association with rs2275913. We also found that two IL-17 haplotypes (G-G-G-A-C) and (A-G-G-A-C) (in the order of rs1974226, rs2275913, rs3819024, rs4711998 and rs8193036) were associated with a reduced GCa risk (adjusted OR = 0.64, 95% CI = 0.46-0.89 and adjusted OR = 0.38, 95% CI = 0.17-0.81, respectively). However, the expression Quantitative Trait Locus (eQTL) analysis for the genotype-phenotype correlation did not find mRNA expression changes associated with either the genotypes. In conclusions, genetic variants of IL-17 are likely to be associated with risk of GCa, and additional larger studies with functional validation are needed to explore the molecular mechanisms underlying the observed associations.Item Open Access Associations of PI3KR1 and mTOR polymorphisms with esophageal squamous cell carcinoma risk and gene-environment interactions in Eastern Chinese populations.(Scientific reports, 2015-01) Zhu, Jinhong; Wang, Mengyun; Zhu, Meiling; He, Jin; Wang, Jiu-Cun; Jin, Li; Wang, Xiao-Feng; Xiang, Jia-Qing; Wei, QingyiSingle nucleotide polymorphisms (SNPs) in the PI3K/PTEN/AKT/mTOR signaling pathway may contribute to carcinogenesis. We genotyped five potentially functional PIK3R1 and mTOR SNPs in 1116 esophageal squamous cell cancer (ESCC) patients and 1117 cancer-free controls to assess their associations with ESCC risk. We observed no association with ESCC risk for any of the selected SNPs. However, the combined analysis of these SNPs revealed that subjects with one-to-three risk genotypes had an increased ESCC risk. Stratified analysis by body mass index (BMI) found that ESCC risk was significantly associated with each of three mTOR SNPs among subjects with BMI < 25.0. Specifically, we found that subjects carrying ≥ 1 risk genotypes had significantly increased ESCC risk, particularly for males, ever-smokers, ever-drinkers, and those with age > 60, or BMI < 25.0. Moreover, three mTOR haplotypes were associated with an increase in ESCC risk. Our meta-analysis of mTOR rs2295080 and cancer risk provided further evidence that mTOR SNPs might modulate cancer susceptibility. In this population, such risk effects might be modified by other risk factors, highlighting the importance of gene-environment interaction in esophageal carcinogenesis. Additional, larger studies are warranted to validate our findings.Item Open Access Associations of potentially functional variants in IL-6, JAKs and STAT3 with gastric cancer risk in an eastern Chinese population.(Oncotarget, 2016-05) Zhou, Fei; Cheng, Lei; Qiu, Li-Xin; Wang, Meng-Yun; Li, Jin; Sun, Meng-Hong; Yang, Ya-Jun; Wang, Jiu-Cun; Jin, Li; Wang, Ya-Nong; Wei, Qing-YiThe interleukin-6 (IL-6)/JAK/STAT3 signaling pathway plays a central role in inflammation-mediated cancers, including gastric cancer (GCa). We evaluated associations between 10 potentially functional single nucleotide polymorphisms (SNPs) of four essential genes in the pathway and GCa risk in a study of 1,125 GCa cases and 1,221 cancer-free controls. We found that a significant higher GCa risk was associated with IL-6 rs2069837G variant genotypes [adjusted odds ratios (OR) = 1.33; 95% confidence interval (CI) = 1.12-1.59 for AG + GG vs. AA)] and JAK1 rs2230587A variant genotypes (adjusted OR = 1.20; 95% CI = 1.02-1.43 for GA + AA vs. GG). We also found that a significant decreased GCa risk was associated with STAT3 rs1053004G variant genotypes (adjusted OR = 0.84; 95% CI = 0.71-0.99 for AG + GG vs. AA). The combined analysis of IL-6 rs2069837G and JAK1 rs2230587A variant risk genotypes revealed that individuals with one-or-two risk genotypes exhibited an increased risk for GCa (adjusted OR = 1.34; 95% CI = 1.13-1.59). Genotypes and mRNA expression correlation analysis using the data from the HapMap 3 database provided further support for the observed risk associations. Larger studies are warranted to validate these findings.Item Open Access Development of hemispheric specialization for lexical pitch-accent in Japanese infants.(J Cogn Neurosci, 2010-11) Sato, Yutaka; Sogabe, Yuko; Mazuka, ReikoInfants' speech perception abilities change through the first year of life, from broad sensitivity to a wide range of speech contrasts to becoming more finely attuned to their native language. What remains unclear, however, is how this perceptual change relates to brain responses to native language contrasts in terms of the functional specialization of the left and right hemispheres. Here, to elucidate the developmental changes in functional lateralization accompanying this perceptual change, we conducted two experiments on Japanese infants using Japanese lexical pitch-accent, which changes word meanings with the pitch pattern within words. In the first behavioral experiment, using visual habituation, we confirmed that infants at both 4 and 10 months have sensitivities to the lexical pitch-accent pattern change embedded in disyllabic words. In the second experiment, near-infrared spectroscopy was used to measure cortical hemodynamic responses in the left and right hemispheres to the same lexical pitch-accent pattern changes and their pure tone counterparts. We found that brain responses to the pitch change within words differed between 4- and 10-month-old infants in terms of functional lateralization: Left hemisphere dominance for the perception of the pitch change embedded in words was seen only in the 10-month-olds. These results suggest that the perceptual change in Japanese lexical pitch-accent may be related to a shift in functional lateralization from bilateral to left hemisphere dominance.Item Open Access Effect of polymorphisms in XPD on clinical outcomes of platinum-based chemotherapy for Chinese non-small cell lung cancer patients.(PloS one, 2012-01) Wu, Wenting; Li, Huan; Wang, Huibo; Zhao, Xueying; Gao, Zhiqiang; Qiao, Rong; Zhang, Wei; Qian, Ji; Wang, Jiucun; Chen, Hongyan; Wei, Qingyi; Han, Baohui; Lu, DaruPURPOSE: Xeroderma pigmentosum group D (XPD) codes for a DNA helicase involved in nucleotide excision repair that removes platinum-induced DNA damage. Genetic polymorphisms of XPD may affect DNA repair capacity and lead to individual differences in the outcome of patients after chemotherapy. This study aims to identify whether XPD polymorphisms affect clinical efficacy among advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. EXPERIMENTAL DESIGN: 353 stage III-IV NSCLC patients receiving platinum-based chemotherapy as the first-line treatment were enrolled in this study. Four potentially functional XPD polymorphisms (Arg(156)Arg, Asp(312)Asn, Asp(711)Asp and Lys(751)Gln) were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or PCR-based sequencing. RESULTS: Variant genotypes of XPD Asp(312)Asn, Asp(711)Asp and Lys(751)Gln were significantly associated with poorer NSCLC survival (P = 0.006, 0.006, 0.014, respectively, by log-rank test). The most common haplotype GCA (in order of Asp(312)Asn, Asp(711)Asp and Lys(751)Gln) also exhibited significant risk effect on NSCLC survival (log-rank P = 0.001). This effect was more predominant for patients with stage IIIB disease (P = 2.21×10(-4), log-rank test). Increased risks for variant haplotypes of XPD were also observed among patients with performance status of 0-1 and patients with adenocarcinoma. However, no significant associations were found between these polymorphisms, chemotherapy response and PFS. CONCLUSIONS: Our study provides evidence for the predictive role of XPD Asp(312)Asn, Asp(711)Asp and Lys(751)Gln polymorphisms/haplotype on NSCLC prognosis in inoperable advanced NSCLC patients treated with platinum-based chemotherapy.Item Open Access Effects of FOXO genotypes on longevity: a biodemographic analysis.(J Gerontol A Biol Sci Med Sci, 2010-12) Zeng, Y; Cheng, L; Chen, H; Cao, H; Hauser, ER; Liu, Y; Xiao, Z; Tan, Q; Tian, XL; Vaupel, JWBased on data from 760 centenarians and 1060 middle-age controls (all Han Chinese), this article contributes biodemographic insights and syntheses concerning the magnitude of effects of the FOXO genotypes on longevity. We also estimate independent and joint effects of the genotypes of FOXO1A and FOXO3A genes on long-term survival, considering carrying or not-carrying the minor allele of the single-nucleotide polymorphism of another relevant gene. We found substantial gender differences in the independent effects; positive effects of FOXO3A and negative effects of FOXO1A largely compensate each other if one carries both, although FOXO3A has a stronger impact. Ten-year follow-up cohort analysis shows that at very advanced ages 92-110, adjusted for various confounders, positive effects of FOXO3A on survival remain statistically significant, but no significant effects of FOXO1A alone; G × G interactions between FOXO1A-209 and FOXO3A-310 or FOXO3A-292 decrease survival likelihood by 32%-36% (p < .05); G × E interactions between FOXO1A-209 and regular exercise increase survival likelihood by 31%-32% (p < .05).Item Open Access Functional polymorphisms of CHRNA3 predict risks of chronic obstructive pulmonary disease and lung cancer in Chinese.(PloS one, 2012-01) Yang, Lei; Qiu, Fuman; Lu, Xiaoxiao; Huang, Dongsheng; Ma, Guanpei; Guo, Yuan; Hu, Min; Zhou, Yumin; Pan, Mingan; Tan, Yigang; Zhong, Haibo; Ji, Weidong; Wei, Qingyi; Ran, Pixin; Zhong, Nanshan; Zhou, Yifeng; Lu, JiachunRecently, several genome-wide association studies (GWAS) have identified many susceptible single nucleotide polymorphisms (SNPs) for chronic obstructive pulmonary disease (COPD) and lung cancer which are two closely related diseases. Among those SNPs, some of them are shared by both the diseases, reflecting there is possible genetic similarity between the diseases. Here we tested the hypothesis that whether those shared SNPs are common predictor for risks or prognosis of COPD and lung cancer. Two SNPs (rs6495309 and rs1051730) located in nicotinic acetylcholine receptor alpha 3 (CHRNA3) gene were genotyped in 1511 patients with COPD, 1559 lung cancer cases and 1677 controls in southern and eastern Chinese populations. We found that the rs6495309CC and rs6495309CT/CC variant genotypes were associated with increased risks of COPD (OR = 1.32, 95% C.I. = 1.14-1.54) and lung cancer (OR = 1.57; 95% CI = 1.31-1.87), respectively. The rs6495309CC genotype contributed to more rapid decline of annual Forced expiratory volume in one second (FEV1) in both COPD cases and controls (P<0.05), and it was associated with advanced stages of COPD (P = 0.033); the rs6495309CT/CC genotypes conferred a poor survival for lung cancer (HR = 1.41, 95%CI = 1.13-1.75). The luciferase assays further showed that nicotine and other tobacco chemicals had diverse effects on the luciferase activity of the rs6495309C or T alleles. However, none of these effects were found for another SNP, rs1051730G>A. The data show a statistical association and suggest biological plausibility that the rs6495309T>C polymorphism contributed to increased risks and poor prognosis of both COPD and lung cancer.Item Open Access Functional variant of MTOR rs2536 and survival of Chinese gastric cancer patients.(International journal of cancer, 2019-01) Cheng, Lei; Qiu, Lixin; Zhang, Ruoxin; Qian, Danwen; Wang, Mengyun; Sun, Menghong; Zhu, Xiaodong; Wang, Yanong; Guo, Weijian; Wei, QingyiWe previously reported that some single nucleotide polymorphisms (SNPs) of candidate genes involved in the MTOR complex1 (MTORC1) were associated with risk of gastric cancer (GCa). In the present study, we further evaluated associations of eight potentially functional SNPs of MTOR, MLST8 and RPTOR with survival of 1002 GCa patients and also investigated molecular mechanisms underlying such associations. Specifically, we found that the MTOR rs2536 C allele at the microRNA binding site was independently associated with a 26% reduction of death risk (HR = 0.74, 95% CI = 0.57-0.96, p = 0.022). The results remained noteworthy with a prior false positive probability of 0.1. Genotype-phenotype correlation analysis in 144 patients' adjacent normal gastric tissue samples revealed that the MTOR expression levels were lower in rs2536 TC/CC carriers than that in wild-type TT carriers (p = 0.043). Dual luciferase assays revealed that the rs2536 C allele had a higher binding affinity to microRNA-150, leading to a decreased transcriptional activity of MTOR, compared to the rs2536 T allele. Further functional analysis revealed that MTOR knockdown by small interference RNA impaired proliferation, migration, and invasion ability in GCa cell lines. In conclusion, The MTOR rs2536 T > C change may be a biomarker for survival of Chinese GCa patients, likely by modulating microRNA-induced gene expression silencing. Additional studies are needed to validate our findings.Item Open Access Gender-dependent association of body mass index and waist circumference with disability in the Chinese oldest old.(Obesity (Silver Spring), 2014-08) Yin, Zhaoxue; Shi, Xiaoming; Kraus, Virginia B; Brasher, Melanie Sereny; Chen, Huashuai; Liu, Yuzhi; Lv, Yuebin; Zeng, YiOBJECTIVES: To explore associations of BMI and waist circumference (WC) with disability among the Chinese oldest old. METHODS: The 5,495 oldest old in the sixth wave of Chinese Longitudinal Healthy Longevity Study conducted in 2011 were included in this study. Disability was assessed by activities of daily living (ADL); height and weight for BMI and WC were measured; information including socio-demographics, lifestyles, and health status was collected. RESULTS: Generalized additive models analysis showed that the association of BMI/WC with ADL disability was nonlinear. Among the males, logistic regression results supported a "J" shape association between ADL disability with BMI/WC-the highest tertile group in BMI or WC was significantly associated with an increased risk of ADL disability: odds ratio 1.78 (95% confidence interval (CI): 1.26-2.52) for BMI and 2.01 (95% CI: 1.44-2.82) for WC. Among females, an inverse "J" shape association was found, only the lowest tertile group before the cutoff point had an increased risk of ADL disability: odds ratio 1.42 (95%CI: 1.02-1.97) for BMI and 1.47 (95% CI:1.06-2.04) for WC. CONCLUSIONS: Associations of BMI and WC with ADL disability are significant even in the oldest old, but differ between the genders.Item Open Access Genetic variant of PRKAA1 and gastric cancer risk in an eastern Chinese population.(Oncotarget, 2015-12) Qiu, Li-Xin; He, Jing; Cheng, Lei; Zhou, Fei; Wang, Meng-Yun; Sun, Meng-Hong; Zhou, Xiao-Yan; Li, Jin; Guo, Wei-Jian; Wang, Ya-Nong; Yang, Ya-Jun; Wang, Jiu-Cun; Jin, Li; Zhu, Xiao-Dong; Wei, Qing-YiPublished data on the association between PRKAA1 rs13361707 T > C polymorphism and gastric cancer (GCa) susceptibility were inconclusive. To derive a more precise estimation of the association, we conducted a large-scale GCa study of 1,124 cases and 1,194 controls to confirm this association in an eastern Chinese population. Our results showed that the C allele of PRKAA1 rs13361707 increased the GC risk in the study population [CT vs. TT, odds ratio (OR) = 1.72, 95% confidence interval (CI) = 1.40-2.12; CC vs. TT, OR = 2.15, 95%CI = 1.70-2.71; CT/CC vs. TT, OR = 1.86, 95%CI = 1.53-2.26; CC vs.TT/CT, OR = 1.49, 95%CI = 1.24-1.79]. In addition, the association of C allele with an increased GCa risk was still significant in subgroups, when stratified by age, sex, tumor site, drinking and smoking status. Moreover, the findings in the present study were validated by our further meta-analysis. In summary, these results indicated that the C allele of PRKAA1 rs13361707 was a low-penetrate risk factor for GCa.Item Open Access Genetic variant rs4072037 of MUC1 and gastric cancer risk in an Eastern Chinese population.(Oncotarget, 2016-03) Qiu, Li-Xin; Hua, Rui-Xi; Cheng, Lei; He, Jing; Wang, Meng-Yun; Zhou, Fei; Zhu, Xiao-Dong; Sun, Meng-Hong; Zhou, Xiao-Yan; Li, Jin; Wang, Ya-Nong; Yang, Ya-Jun; Wang, Jiu-Cun; Jin, Li; Guo, Wei-Jian; Wei, Qing-YiPublished data on the association between the MUC1 rs4072037A > G polymorphism and gastric cancer (GCa) risk were inconclusive. To derive a more precise estimation of the association, we conducted a large GCa study of 1,124 cases and 1,192 controls to confirm this association in an Eastern Chinese population. Our results showed that the G allele was strongly associated with a decreased GCa risk in the study population [GG vs. AA, odds ratio (OR) = 0.47, 95% confidence interval (CI) = 0.31-0.73; AG/GG vs. AA, OR = 0.82, 95% CI = 0.68-0.99; GG vs. AA/AG, OR = 0.48, 95% CI = 0.32-0.74]. These associations remained significant in subgroups of age, tumor site, drinking and smoking status. Moreover, this association was supported by an additional meta-analysis of published studies. In summary, these results suggest that the MUC1 rs4072037G allele may be a low-penetrating protection factor for GCa risk in Chinese populations.Item Open Access Genetic variants of DNA repair genes predict the survival of patients with esophageal squamous cell cancer receiving platinum-based adjuvant chemotherapy.(Journal of translational medicine, 2016-05-31) Zhou, Fei; Zhu, Meiling; Wang, Mengyun; Qiu, Lixin; Cheng, Lei; Jia, Ming; Xiang, Jiaqing; Wei, QingyiAdjuvant chemotherapy in patients with resected esophageal squamous cell cancer (ESCC) remains controversial for its uncertain role in improving overall survival (OS). Nucleotide excision repair (NER) removes DNA-adducts in tumor cells induced by the platinum-based chemotherapy and thus may modulate efficacy of the treatment. The present study evaluated if single nucleotide polymorphisms (SNPs) of NER genes were prognostic biomarkers in ESCC patients treated with platinum-based adjuvant chemotherapy (PAC).The analysis included 572 patients, for whom six SNPs of NER genes [i.e., XPC (rs1870134 and rs2228001), ERCC2/XPD rs238406 and ERCC5/XPG (rs2094258, rs2296147 and rs873601)] were detected with the TaqMan assay. Kaplan-Meier analyses and Cox proportional hazards models were used to evaluate their associations with disease free survival (DFS) and OS of these ESCC patients receiving PAC. Receiving operating characteristic curve analysis was used to evaluate the role of the risk genotypes in the DFS and OS.We found that ERCC5/XPG rs2094258 and rs873601 and ERCC2/XPD rs238406 SNPs were independently associated with poorer DFS and OS of ESCC patients [ERCC5/XPG rs2094258: CT+TT vs. CC: adjusted hazards ratio (adjHR) = 1.68 and P = 0.012 for DFS; adjHR = 1.99 and P = 0.0001 for OS; ERCC5/XPG rs873601: GA+GG vs. AA: adjHR = 1.59 and P = 0.024 for DFS; adjHR = 1.91 and P = 0.0005 for OS; ERCC2/XPD rs238406: TT vs. GG+GT: adjHR = 1.43 and P = 0.020 for DFS; adjHR = 1.52 and P = 0.008 for OS]. These HRs increased as the number of risk genotypes increased in the combined analysis. The model combining the risk genotypes with clinical characteristics or the TNM stage system was better in predicting outcomes in ESCC patients with PAC.SNPs of ERCC2/XPD and ERCC5/XPG may independently and jointly predict survival of ESCC patients treated with PAC in this study population. Further validation in other study populations is warranted.Item Open Access Genetic variants of GADD45A, GADD45B and MAPK14 predict platinum-based chemotherapy-induced toxicities in Chinese patients with non-small cell lung cancer.(Oncotarget, 2016-05) Jia, Ming; Zhu, Meiling; Wang, Mengyun; Sun, Menghong; Qian, Ji; Ding, Fei; Chang, Jianhua; Wei, QingyiThe JNK and P38α pathways play a crucial role in tissue homeostasis, apoptosis and autophagy under genotoxic stresses, but it is unclear whether single nucleotide polymorphisms (SNPs) of genes in these pathways play a role in platinum-based chemotherapy-induced toxicities in patients with advanced non-small cell lung cancer (NSCLC). We genotyped 11 selected, independent, potentially functional SNPs of nine genes in the JNK and P38α pathways in 689 patients with advanced NSCLC treated with platinum-combination chemotherapy regimens. Associations between these SNPs and chemotherapy toxicities were tested in a discovery group of 345 patients and then validated in a replication group of 344 patients. In both discovery and validation groups as well as their pooled analysis, carriers of GADD45B rs2024144T variant allele had a significantly higher risk for severe hematologic toxicity and carriers of MAPK14 rs3804451A variant allele had a significantly higher risk for both overall toxicity and gastrointestinal toxicity. In addition, carriers of GADD45A rs581000C had a lower risk of anemia, while carriers of GADD45B rs2024144T had a significantly higher risk for leukocytopenia or agranulocytosis. The present study provides evidence that genetic variants in genes involved in the JNK and P38α pathways may predict platinum-based chemotherapy toxicity outcomes in patients with advanced NSCLC. Larger studies of other patient populations are needed to validate our findings.Item Open Access GxE interactions between FOXO genotypes and drinking tea are significantly associated with prevention of cognitive decline in advanced age in China.(J Gerontol A Biol Sci Med Sci, 2015-04) Zeng, Y; Chen, H; Ni, T; Ruan, R; Feng, L; Nie, C; Cheng, L; Li, Y; Tao, W; Gu, J; Land, KC; Yashin, A; Tan, Q; Yang, Z; Bolund, L; Yang, H; Hauser, E; Willcox, DC; Willcox, BJ; Tian, X; Vaupel, JWLogistic regression analysis based on data from 822 Han Chinese oldest old aged 92+ demonstrated that interactions between carrying FOXO1A-266 or FOXO3-310 or FOXO3-292 and tea drinking at around age 60 or at present time were significantly associated with lower risk of cognitive disability at advanced ages. Associations between tea drinking and reduced cognitive disability were much stronger among carriers of the genotypes of FOXO1A-266 or FOXO3-310 or FOXO3-292 compared with noncarriers, and it was reconfirmed by analysis of three-way interactions across FOXO genotypes, tea drinking at around age 60, and at present time. Based on prior findings from animal and human cell models, we postulate that intake of tea compounds may activate FOXO gene expression, which in turn may positively affect cognitive function in the oldest old population. Our empirical findings imply that the health benefits of particular nutritional interventions, including tea drinking, may, in part, depend upon individual genetic profiles.