Key Laboratory of Modern Toxicology

Laboratory of, China

Key Laboratory of Modern Toxicology

Laboratory of, China
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Xu J.,Fudan University | Xu J.,Wake forest University | Mo Z.,Guangxi Medical University | Ye D.,Fudan University | And 78 more authors.
Nature Genetics | Year: 2012

Prostate cancer risk-associated variants have been reported in populations of European descent, African-Americans and Japanese using genome-wide association studies (GWAS). To systematically investigate prostate cancer risk-associated variants in Chinese men, we performed the first GWAS in Han Chinese. In addition to confirming several associations reported in other ancestry groups, this study identified two new risk-associated loci for prostate cancer on chromosomes 9q31.2 (rs817826, P = 5.45 × 10-14) and 19q13.4 (rs103294, P = 5.34 × 10-16) in 4,484 prostate cancer cases and 8,934 controls. The rs103294 marker at 19q13.4 is in strong linkage equilibrium with a 6.7-kb germline deletion that removes the first six of seven exons in LILRA3, a gene regulating inflammatory response, and was significantly associated with the mRNA expression of LILRA3 in T cells (P < 1 × 10-4). These findings may advance the understanding of genetic susceptibility to prostate cancer. © 2012 Nature America, Inc. All rights reserved.

Xu C.,Institute of Toxicology | Xu C.,Key Laboratory of Modern Toxicology | Liu Q.,Institute of Toxicology | Liu Q.,Key Laboratory of Modern Toxicology | And 11 more authors.
Chemotherapy | Year: 2014

Objective: The gut microbiome is essential for human health due to its effects on disease development, drug metabolism and the immune system. It may also play a role in the interaction with environmental toxicants. However, the effect of epoxiconazole, a fungicide active ingredient from the class of azoles developed to protect crops, on the abundance and composition of the gut microbiome has never been studied. We put forward the hypothesis that changes in gut microbiota may be early signs of toxicity induced by epoxiconazole. Methods: In this study, female rats were fed with epoxiconazole-adulterated diets (0, 4 and 100 mg/kg/day) for 90 days. The gut microbiome was determined by 16S rRNA gene sequencing. Body and organ weight, and blood biochemistry were also measured after 90 days of oral epoxiconazole exposure. Results: Interestingly, the abundance of gut Firmicutes decreased, and Bacteroidetes and Proteobacteria increased. At family level, Lachnospiraceae and Enterobacteriaceae were selectively enriched following epoxiconazole exposure. Our results indicate that epoxiconazole exposure may induce changes in the gut microbiome and potential liver toxicity. Conclusion: Changes in the gut microbiome may be used as early indicators for monitoring the health risk of the host. © 2015 S. Karger AG, Basel.

Wang J.,Nanjing Medical University | Wang J.,Key Laboratory of Modern Toxicology | Gao Y.,Centers for Disease Control and Prevention | Wang L.,Nanjing Medical University | And 6 more authors.
European Journal of Cancer Prevention | Year: 2013

Glucocorticoid hormones have been reported to contribute to the regulation of cellular proliferation and differentiation and to inhibit the growth of cells in several colon tumors and adenocarcinoma cell lines. As a regulator of glucocorticoid levels, type I isoform HSD11B1 is a bidirectional enzyme but acts predominantly as an oxidoreductase to yield active glucocorticoids, cortisol or corticosterone. To date, studies investigating the associations between the polymorphisms of HSD11B1 and the risk for cancer have shown inconclusive results. In our study, we aimed to investigate whether the polymorphisms of HSD11B1 may influence the genetic susceptibility to colorectal cancer (CRC) in a Chinese population. Four single-nucleotide polymorphisms of HSD11B1 (rs846910 G/A, rs11807619 G/T, rs932335 C/G, and rs13306421 G/A) were detected using a PCR-ligase detection reaction in a case-control study comprising 110 CRC patients and 118 controls. Logistic regression was used to evaluate genetic associations with the occurrence of CRC. Real-time PCR was used to test the mRNA expression of HSD11B1 in 18 CRC tissues. The frequencies of the rs932335 GC genotype were significantly higher among the patients compared with controls (P=0.019). Compared with individuals carrying the GG genotype, individuals with the GC/CC genotype had a significantly increased susceptibility to CRC occurrence (odds ratio=2.23, 95% confidence interval=1.27-3.94, P=0.008). In cancer tissues, patients carrying the GG genotype also displayed an increased mRNA level of HSD11B1 (P=0.019). These results suggested that the HSD11B1 rs932335 G/C polymorphism had an effect on CRC occurrence. These findings also suggest that the functional polymorphism rs932335 in intron4 of HSD11B1 may influence the susceptibility to and progression of CRC in a Chinese population. Large population-based prospective studies are required to validate our findings. © 2013 Wolters Kluwer Health Lippincott Williams & Wilkins.

Xue Y.,Prevention and Treatment Cancer Center | Xue Y.,Key Laboratory of Modern Toxicology | Gu D.,Nanjing Medical University | Ma G.,Prevention and Treatment Cancer Center | And 11 more authors.
Mutagenesis | Year: 2015

Long non-coding RNA HOX transcript antisenseRNA (HOTAIR) has been widely identified to participate in tumour pathogenesis, acting as a promoter in colorectal cancer carcinogenesis. However, the association between genetic variants in HOTAIR and cancer risk has not yet been reported. In the present study, we performed a two-stage case-control study to investigate the association between HOTAIR tagSNPs and the risk of colorectal cancer. We found that individuals with rs7958904 CC genotype had a significantly decreased risk of colorectal cancer in both Stage 1 and 2, compared with those carrying GG genotype [odds ratio (OR) = 0.70, 95% confidence interval (CI) = 0.51-0.97 in Stage 1; OR = 0.58, 95% CI = 0.37-0.91 in Stage 2; OR = 0.67, 95% CI = 0.51-0.87 in combined stage]. The subsequently stratified analyses showed that the protective effect of rs7958904 was more pronounced in several subgroups. In summary, our study showed that genetic variants in HOTAIR were associated with risk of colorectal cancer and rs7958904 may act as a potential biomarker for predicting the risk of colorectal cancer. © 2015 The Author.

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