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Genome-Wide Association Study in East Asians Identifies Novel Susceptibility Loci for Breast Cancer
Long, Jirong,Cai, Qiuyin,Sung, Hyuna,Shi, Jiajun,Zhang, Ben,Choi, Ji-Yeob,Wen, Wanqing,Delahanty, Ryan J.,Lu, Wei,Gao, Yu-Tang,Shen, Hongbing,Park, Sue K.,Chen, Kexin,Shen, Chen-Yang,Ren, Zefang,Haima Public Library of Science 2012 PLoS genetics Vol.8 No.2
<P>Genetic factors play an important role in the etiology of both sporadic and familial breast cancer. We aimed to discover novel genetic susceptibility loci for breast cancer. We conducted a four-stage genome-wide association study (GWAS) in 19,091 cases and 20,606 controls of East-Asian descent including Chinese, Korean, and Japanese women. After analyzing 690,947 SNPs in 2,918 cases and 2,324 controls, we evaluated 5,365 SNPs for replication in 3,972 cases and 3,852 controls. Ninety-four SNPs were further evaluated in 5,203 cases and 5,138 controls, and finally the top 22 SNPs were investigated in up to 17,423 additional subjects (7,489 cases and 9,934 controls). SNP rs9485372, near the TGF-β activated kinase (<I>TAB2</I>) gene in chromosome 6q25.1, showed a consistent association with breast cancer risk across all four stages, with a <I>P</I>-value of 3.8×10<SUP>−12</SUP> in the combined analysis of all samples. Adjusted odds ratios (95% confidence intervals) were 0.89 (0.85–0.94) and 0.80 (0.75–0.86) for the A/G and A/A genotypes, respectively, compared with the genotype G/G. SNP rs9383951 (<I>P</I> = 1.9×10<SUP>−6</SUP> from the combined analysis of all samples), located in intron 5 of the <I>ESR1</I> gene, and SNP rs7107217 (<I>P</I> = 4.6×10<SUP>−7</SUP>), located at 11q24.3, also showed a consistent association in each of the four stages. This study provides strong evidence for a novel breast cancer susceptibility locus represented by rs9485372, near the <I>TAB2</I> gene (6q25.1), and identifies two possible susceptibility loci located in the <I>ESR1</I> gene and 11q24.3, respectively.</P><P><B>Author Summary</B></P> <P>Breast cancer is one of the most common malignancies among women worldwide. Genetic factors play an important role in the etiology of breast cancer. To identify common genetic susceptibility alleles for breast cancer, we performed a four-stage genome-wide association study in 19,091 cases and 20,606 controls among East-Asian women. Single nucleotide polymorphism (SNP) rs9485372, near the TGF-beta activated kinase 1 (<I>TAB2</I>) gene at chromosome 6q25.1, was associated with breast cancer risk (<I>P</I> = 3.8×10<SUP>−12</SUP>). SNPs rs9383951, located in intron 5 of the estrogen receptor 1 (<I>ESR1</I>) gene, and rs7107217, located at 11q24.3, were also consistently associated with breast cancer risk in all four stages with a combined <I>P</I> of 1.9×10<SUP>−6</SUP> and 4.6×10<SUP>−7</SUP>, respectively. This study provides strong evidence for a novel breast cancer susceptibility locus represented by rs9485372, near the <I>TAB2</I> gene (6q25.1), and identifies two possible susceptibility loci located in the <I>ESR1</I> gene and 11q24.3, respectively.</P>
Cr(VI) Resistance and Removal by Indigenous Bacteria Isolated from Chromium-Contaminated Soil
( Dong Yan Long ),( Xian Jin Tang ),( Kuan Cai ),( Guang Cun Chen ),( Chao Feng Shen ),( Ji Yan Shi ),( Ling Gui Chen ),( Ying Xu Chen ) 한국미생물 · 생명공학회 2013 Journal of microbiology and biotechnology Vol.23 No.8
The removal of toxic Cr(VI) by microorganisms is a promising approach for Cr(VI) pollution remediation. In the present study, four indigenous bacteria, named LY1, LY2, LY6, and LY7, were isolated from Cr(VI)-contaminated soil. Among the four Cr(VI)-resistant isolates, strain LY6 displayed the highest Cr(VI)-removing ability, with 100 mg/l Cr(VI) being completely removed within 144 h. It could effectively remove Cr(VI) over a wide pH range from 5.5 to 9.5, with the optimal pH of 8.5. The amount of Cr(VI) removed increased with initial Cr(VI) concentration. Data from the time-course analysis of Cr(VI) removal by strain LY6 followed first-order kinetics. Based on the 16S rRNA gene sequence, strain LY6 was identified as Pseudochrobactrum asaccharolyticum, a species that had never been reported for Cr(VI) removal before. Transmission electron microscopy and energy dispersive X-ray spectroscopy analysis further confirmed that strain LY6 could accumulate chromium within the cell while conducting Cr(VI) removal. The results suggested that the indigenous bacterial strain LY6 would be a new candidate for potential application in Cr(VI) pollution bioremediation.
Zheng, Wei,Zhang, Ben,Cai, Qiuyin,Sung, Hyuna,Michailidou, Kyriaki,Shi, Jiajun,Choi, Ji-Yeob,Long, Jirong,Dennis, Joe,Humphreys, Manjeet K.,Wang, Qin,Lu, Wei,Gao, Yu-Tang,Li, Chun,Cai, Hui,Park, Sue K Oxford University Press 2013 Human Molecular Genetics Vol.22 No.12
<P>In a consortium including 23 637 breast cancer patients and 25 579 controls of East Asian ancestry, we investigated 70 single-nucleotide polymorphisms (SNPs) in 67 independent breast cancer susceptibility loci recently identified by genome-wide association studies (GWASs) conducted primarily in European-ancestry populations. SNPs in 31 loci showed an association with breast cancer risk at <I>P</I> < 0.05 in a direction consistent with that reported previously. Twenty-one of them remained statistically significant after adjusting for multiple comparisons with the Bonferroni-corrected significance level of <0.0015. Eight of the 70 SNPs showed a significantly different association with breast cancer risk by estrogen receptor (ER) status at <I>P</I> < 0.05. With the exception of rs2046210 at 6q25.1, the seven other SNPs showed a stronger association with ER-positive than ER-negative cancer. This study replicated all five genetic risk variants initially identified in Asians and provided evidence for associations of breast cancer risk in the East Asian population with nearly half of the genetic risk variants initially reported in GWASs conducted in European descendants. Taken together, these common genetic risk variants explain ∼10% of excess familial risk of breast cancer in Asian populations.</P>