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1.
Nutrients ; 11(8)2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31434255

RESUMO

Higher circulating 25-hydroxyvitamin D levels (25(OH)D) have been found to be associated with lower risk for colorectal cancer (CRC) in prospective studies. Whether this association is modified by genetic variation in genes related to vitamin D metabolism and action has not been well studied in humans. We investigated 1307 functional and tagging single-nucleotide polymorphisms (SNPs; individually, and by gene/pathway) in 86 vitamin D-related genes in 1420 incident CRC cases matched to controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We also evaluated the association between these SNPs and circulating 25(OH)D in a subset of controls. We confirmed previously reported CRC risk associations between SNPs in the VDR, GC, and CYP27B1 genes. We also identified additional associations with 25(OH)D, as well as CRC risk, and several potentially novel SNPs in genes related to vitamin D transport and action (LRP2, CUBN, NCOA7, and HDAC9). However, none of these SNPs were statistically significant after Benjamini-Hochberg (BH) multiple testing correction. When assessed by a priori defined functional pathways, tumor growth factor ß (TGFß) signaling was associated with CRC risk (P ≤ 0.001), with most statistically significant genes being SMAD7 (PBH = 0.008) and SMAD3 (PBH = 0.008), and 18 SNPs in the vitamin D receptor (VDR) binding sites (P = 0.036). The 25(OH)D-gene pathway analysis suggested that genetic variants in the genes related to VDR complex formation and transcriptional activity are associated with CRC depending on 25(OH)D levels (interaction P = 0.041). Additional studies in large populations and consortia, especially with measured circulating 25(OH)D, are needed to confirm our findings.

2.
Nutrients ; 11(4)2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31027226

RESUMO

Selenoprotein genetic variations and suboptimal selenium (Se) levels may contribute to the risk of colorectal cancer (CRC) development. We examined the association between CRC risk and genotype for single nucleotide polymorphisms (SNPs) in selenoprotein and Se metabolic pathway genes. Illumina Goldengate assays were designed and resulted in the genotyping of 1040 variants in 154 genes from 1420 cases and 1421 controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Multivariable logistic regression revealed an association of 144 individual SNPs from 63 Se pathway genes with CRC risk. However, regarding the selenoprotein genes, only TXNRD1 rs11111979 retained borderline statistical significance after adjustment for correlated tests (PACT = 0.10; PACT significance threshold was P < 0.1). SNPs in Wingless/Integrated (Wnt) and Transforming growth factor (TGF) beta-signaling genes (FRZB, SMAD3, SMAD7) from pathways affected by Se intake were also associated with CRC risk after multiple testing adjustments. Interactions with Se status (using existing serum Se and Selenoprotein P data) were tested at the SNP, gene, and pathway levels. Pathway analyses using the modified Adaptive Rank Truncated Product method suggested that genes and gene x Se status interactions in antioxidant, apoptosis, and TGF-beta signaling pathways may be associated with CRC risk. This study suggests that SNPs in the Se pathway alone or in combination with suboptimal Se status may contribute to CRC development.

3.
J Surg Res ; 214: 49-56, 2017 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-28624059

RESUMO

BACKGROUND: There is significant variation surrounding the indications, surgical approaches, and outcomes for children undergoing antireflux procedures (ARPs) resulting in geographic variation of care. Our purpose was to quantify this geographic variation in the utilization of ARPs in children. METHODS: A cross-sectional analysis of the 2009 Kid's Inpatient Database was performed to identify patients with gastroesophageal reflux disease or associated diagnoses. Regional surgical utilization rates were determined, and a mixed effects model was used to identify factors associated with the use of ARPs. RESULTS: Of the 148,959 patients with a diagnosis of interest, 4848 (3.3%) underwent an ARP with 2376 (49%) undergoing a laparoscopic procedure. The Northeast (2.0%) and Midwest (2.2%) had the lowest overall utilization of surgery, compared with the South (3.3%) and West (3.4%). After adjustment for age, case-mix, and surgical approach, variation persisted with the West and the South demonstrating almost two times the odds of undergoing an ARP compared with the Northeast. Surgical utilization rates are independent of state-level volume with some of the highest case volume states having surgical utilization rates below the national rate. In the West, the use of laparoscopy correlated with overall utilization of surgery, whereas surgical approach was not correlated with ARP use in the South. CONCLUSIONS: Significant regional variation in ARP utilization exists that cannot be explained entirely by differences in patient age, race/ethnicity, case-mix, and surgical approach. In order to decrease variation in care, further research is warranted to establish consensus guidelines regarding indications for the use ARPs for children.


Assuntos
Fundoplicatura/estatística & dados numéricos , Refluxo Gastroesofágico/cirurgia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Bases de Dados Factuais , Feminino , Fundoplicatura/métodos , Humanos , Lactente , Recém-Nascido , Laparoscopia/estatística & dados numéricos , Masculino , Modelos Estatísticos , Estados Unidos
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