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Zhu Z.,Nanjing Medical University | Zhu Z.,Chinese University of Hong Kong | Tang N.L.-S.,Chinese University of Hong Kong | Xu L.,Nanjing Medical University | And 44 more authors.
Nature Communications | Year: 2015

Adolescent idiopathic scoliosis (AIS) is a structural deformity of the spine affecting millions of children. As a complex disease, the genetic aetiology of AIS remains obscure. Here we report the results of a four-stage genome-wide association study (GWAS) conducted in a sample of 4,317 AIS patients and 6,016 controls. Overall, we identify three new susceptibility loci at 1p36.32 near AJAP1 (rs241215, Pcombined =2.95 × 10-9), 2q36.1 between PAX3 and EPHA4 (rs13398147, Pcombined =7.59 × 10-13) and 18q21.33 near BCL-2 (rs4940576, Pcombined =2.22 × 10-12). In addition, we refine a previously reported region associated with AIS at 10q24.32 (rs678741, Pcombined =9.68 × 10-37), which suggests LBX1AS1, encoding an antisense transcript of LBX1, might be a functional variant of AIS. This is the first GWAS investigating genetic variants associated with AIS in Chinese population, and the findings provide new insight into the multiple aetiological mechanisms of AIS. © 2015 Macmillan Publishers Limited. All rights reserved.

Li J.,State Key Laboratory of Environment Health Incubation | Zou L.,State Key Laboratory of Environment Health Incubation | Chen W.,State Key Laboratory of Environment Health Incubation | Zhu B.,State Key Laboratory of Environment Health Incubation | And 6 more authors.
PLoS ONE | Year: 2014

Epidemiological studies have investigated the potential anticancer effects of mushroom intake. This review aims to clarify the evidence on the association of dietary mushroom intake with breast cancer risk and to quantify its dose-response relationship. Relevant studies were identified by a search of PubMed, Web of Science and Google Scholar up to December 31, 2013. Observational studies with relative risks (RRs) or hazard ratios (HRs) or odd ratios (ORs) and 95% confidence intervals (CIs) of breast cancer for three or more categories of mushroom intake were eligible. The quality of included studies was assessed by using Newcastle-Ottawa Scale. A dose-response meta-analysis was performed by utilizing generalized least squares trend estimation. Eight case-control studies and two cohort studies with a total of 6890 cases were ultimately included. For dose-response analysis, there was no evidence of non-linear association between mushroom consumption and breast cancer risk (P = 0.337) and a 1 g/d increment in mushroom intake conferred an RR of 0.97 (95% CI: 0.96-0.98) for breast cancer risk, with moderate heterogeneity (I2 = 56.3%, P = 0.015). Besides, available menopause data extracted from included studies were used to evaluate the influence of menopausal statues. The summary RRs of mushroom consumption on breast cancer were 0.96 (95% CI: 0.91-1.00) for premenopausal women and 0.94 (95% CI: 0.91-0.97) for postmenopausal women, respectively. Our findings demonstrated that mushroom intake may be inversely associated with risk of breast cancer, which need to be confirmed with large-scale prospective studies further. © 2014 Li et al.

Gong J.,State Key Laboratory of Environment Health Incubation | Gong J.,Huazhong University of Science and Technology | Tian J.,State Key Laboratory of Environment Health Incubation | Tian J.,Huazhong University of Science and Technology | And 19 more authors.
Carcinogenesis | Year: 2016

Genome-wide association studies (GWASs) have identified multiple susceptibility loci of colorectal cancer (CRC), however, causative polymorphisms have not been fully elucidated. Long non-coding RNAs (lncRNAs) are a recently discovered class of non-protein coding RNAs that involved in a wide variety of biological processes. We hypothesized that single nucleotide polymorphisms (SNPs) in lncRNA may associate with the CRC risk by influencing lncRNA functions. To evaluate the effects of SNPs on CRC susceptibility in Chinese populations, we first screened out all potentially functional SNPs in exons of lncRNAs located in CRC susceptibility loci identified by GWAS. Eight SNPs were selected and genotyped in 875 CRC cases and 855 controls and replicated in an independent case-control study consisting of 768 CRC cases and 768 controls. Analyses showed that CG and GG genotypes of the rs2147578 were significantly associated with increased risk for CRC occurrence in both case-control studies [combined analysis OR = 1.29; 95% confidence interval (CI) = 1.11-1.51, P = 0.001] compared to the rs2147578 CC genotype. Bioinformatics analyses showed that rs2147578 is located in the transcript of lnc-LAMC2-1:1 and could influence the binding of lnc-LAMC2-1:1/miR-128-3p. Further luciferase reporter assays demonstrated that the construct with the risk rs2147578G allele had relatively high expression activity compared with that of the rs2147578C allele. Expression quantitative trait loci analyses also showed that rs2147578 is correlated with the expression of a well established oncogene LAMC2 (laminin subunit gamma 2). These findings indicated that rs2147578 in lnc-LAMC2-1:1 might be a genetic modifier for the development of CRC. © The Author 2016. Published by Oxford University Press. All rights reserved.

Zhang Y.,State Key Laboratory of Environment Health Incubation | Yi P.,Huazhong University of Science and Technology | Chen W.,State Key Laboratory of Environment Health Incubation | Ming J.,Huazhong University of Science and Technology | And 16 more authors.
Tumor Biology | Year: 2014

Recent publications have found associations between single-nucleotide polymorphisms (SNPs) in 8q24 and the risk of breast cancer (BC) in some populations, but the conclusions are inconsistent. In order to further investigate the association between variants in this region and BC risk in Chinese population, we conducted an independent hospital-based case-control study to discern the effects of these SNPs on BC risk. We genotyped three 8q24 SNPs (rs13281615, rs6983267, and rs9642880) in 485 cases and 530 cancer-free controls. The results indicated that the rs13281615 G allele significantly increased BC risk, with an odds ratio (OR) of 1.23 (95 % confidence interval (CI) = 1.03-1.46) under the allelic model. Besides, stratification analysis reported that the significant association remained in the estrogen receptor (ER)+/progesterone receptor (PR)+ subgroup with a P value of 0.007 under the allelic model (OR = 1.33, 95 % CI = 1.08-1.63). For the rs9642880 variant, only a feeble association was observed for the GT genotype compared with the GG genotype (OR = 1.33, 95 % CI = 1.01-1.74). In addition, there was a negligible association between rs6983267 and BC risk in the ER-/PR- subgroup. However, no significant finding was observed in the overall participants. The findings suggested that polymorphisms in 8q24 may contribute to susceptibility to BC risk. However, functional studies are warranted to further elucidate the mechanisms of the association. © 2014 International Society of Oncology and BioMarkers (ISOBM).

Zhu B.,State Key Laboratory of Environment Health Incubation | Sun Y.,State Key Laboratory of Environment Health Incubation | Qi L.,Harvard University | Zhong R.,State Key Laboratory of Environment Health Incubation | Miao X.,State Key Laboratory of Environment Health Incubation
Scientific Reports | Year: 2015

Previous epidemiological studies on the relation between dietary legume consumption and risk of colorectal cancer (CRC) remain controversial. We conducted a meta-analysis based on prospective cohort studies to investigate the association between dietary legume consumption and risk of CRC. Fourteen cohort studies were finally included, containing a total of 1903459 participants and 12261 cases who contributed 11628960 person-years. We found that higher legume consumption was associated with a decreased risk of CRC (RR, relative risk = 0.91; 95% CI, confidence interval = 0.84-0.98). Subgroup analyses suggested that higher legume consumption was inversely associated with CRC risk in Asian (RR = 0.82; 95% CI = 0.74-0.91) and soybean intake was associated with a decreased risk of CRC (RR = 0.85; 95% CI = 0.73-0.99). Findings from our meta-analysis supported an association between higher intake of legume and a reduced risk of CRC. Further studies controlled for appropriate confounders are warranted to validate the associations.

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