23 research outputs found

    A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

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    We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻ÂčÂČ) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻ÂčÂč) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻ÂčÂč) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻ÂčÂč), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

    A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

    Get PDF
    We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻ÂčÂČ) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻ÂčÂč) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻ÂčÂč) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻ÂčÂč), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

    International nosocomial infection control consortium (INICC) report, data summary of 36 countries, for 2004-2009

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    The results of a surveillance study conducted by the International Nosocomial Infection Control Consortium (INICC) from January 2004 through December 2009 in 422 intensive care units (ICUs) of 36 countries in Latin America, Asia, Africa, and Europe are reported. During the 6-year study period, using Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN; formerly the National Nosocomial Infection Surveillance system [NNIS]) definitions for device-associated health care-associated infections, we gathered prospective data from 313,008 patients hospitalized in the consortium's ICUs for an aggregate of 2,194,897 ICU bed-days. Despite the fact that the use of devices in the developing countries' ICUs was remarkably similar to that reported in US ICUs in the CDC's NHSN, rates of device-associated nosocomial infection were significantly higher in the ICUs of the INICC hospitals; the pooled rate of central line-associated bloodstream infection in the INICC ICUs of 6.8 per 1,000 central line-days was more than 3-fold higher than the 2.0 per 1,000 central line-days reported in comparable US ICUs. The overall rate of ventilator-associated pneumonia also was far higher (15.8 vs 3.3 per 1,000 ventilator-days), as was the rate of catheter-associated urinary tract infection (6.3 vs. 3.3 per 1,000 catheter-days). Notably, the frequencies of resistance of Pseudomonas aeruginosa isolates to imipenem (47.2% vs 23.0%), Klebsiella pneumoniae isolates to ceftazidime (76.3% vs 27.1%), Escherichia coli isolates to ceftazidime (66.7% vs 8.1%), Staphylococcus aureus isolates to methicillin (84.4% vs 56.8%), were also higher in the consortium's ICUs, and the crude unadjusted excess mortalities of device-related infections ranged from 7.3% (for catheter-associated urinary tract infection) to 15.2% (for ventilator-associated pneumonia). Copyright © 2012 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved

    Shared heritability and functional enrichment across six solid cancers

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    Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis

    Sudden appearance and population outbreak of \u3ci\u3eEunica monima\u3c/i\u3e (Lepidoptera: Nymphalidae) on Desecheo Island, Puerto Rico

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    We documented the appearance and elevated abundance of the uncommon dingy purplewing butterfly, Eunica monima (Stoll) (Lepidoptera: Nymphalidae), and pronounced herbivory on its host plant Bursera simaruba (L.) Sarg. (Burseraceae) shortly after island-wide rat (Rattus rattus [L.]; Muridae) removal from Desecheo Island, Puerto Rico. We confirmed the species as E. monima by using both molecular and morphological analyses of larvae and adults. This is a first-time record of E. monima for the island of Desecheo, one of relatively few documented appearances in Puerto Rico during the last 100 yr, and an uncommon documentation of an outbreak of this species in the Caribbean. Although experimental manipulation would be needed to identify the cause of the E. monima population outbreak, we discuss possible cause-and-effect scenarios. Documentamos la apariciĂłn y elevada abundancia de la mariposa poco comĂșn Dingy Purplewing, Eunica monima (Stoll) (Lepidoptera: Nymphalidae), y la pronunciada herbivorĂ­a en su planta hospedera Bursera simaruba (L.) Sarg. (Burseraceae), poco despuĂ©s de una erradicaciĂłn de ratas (Rattus rattus [L.]; Muridae) en la isla de Desecheo, Puerto Rico. Confirmamos la especie como E. monima mediante anĂĄlisis tanto moleculares como morfolĂłgicos de las orugas y adultos. Este es el primer registro de E. monima para la isla de Desecheo, una de las relativamente pocas apariciones documentadas en Puerto Rico durante los Ășltimos 100 años y tambiĂ©n se documentĂł un brote poco comĂșn para esta especie en el Caribe. Aunque la manipulaciĂłn experimental serĂ­a necesaria para identificar la causa del brote de E. monima, discutimos los posibles escenarios de causa y efecto

    Shared heritability and functional enrichment across six solid cancers

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    Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (rg = 0.24, p = 7 x 10(-5)), breast and lung cancer (rg = 0.18, p =1.5 x 10(-6)) and breast and colorectal cancer (rg = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis
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