Vitamin D Metabolic Pathway Genes and Pancreatic Cancer Risk
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{"title"=>"Vitamin D metabolic pathway genes and pancreatic cancer risk", "type"=>"journal", "authors"=>[{"first_name"=>"Hannah", "last_name"=>"Arem", "scopus_author_id"=>"36631451300"}, {"first_name"=>"Kai", "last_name"=>"Yu", "scopus_author_id"=>"7403385290"}, {"first_name"=>"Xiaoqin", "last_name"=>"Xiong", "scopus_author_id"=>"56189716600"}, {"first_name"=>"Kristin", "last_name"=>"Moy", "scopus_author_id"=>"25223450800"}, {"first_name"=>"Neal D.", "last_name"=>"Freedman", "scopus_author_id"=>"55133034400"}, {"first_name"=>"Susan T.", "last_name"=>"Mayne", "scopus_author_id"=>"7005521636"}, {"first_name"=>"Demetrius", "last_name"=>"Albanes", "scopus_author_id"=>"7006558522"}, {"first_name"=>"Alan A.", "last_name"=>"Arslan", "scopus_author_id"=>"56238185300"}, {"first_name"=>"Melissa", "last_name"=>"Austin", "scopus_author_id"=>"7202194000"}, {"first_name"=>"William R.", "last_name"=>"Bamlet", "scopus_author_id"=>"6507377111"}, {"first_name"=>"Laura", "last_name"=>"Beane-Freeman", "scopus_author_id"=>"8354328100"}, {"first_name"=>"Paige", "last_name"=>"Bracci", "scopus_author_id"=>"6603636147"}, {"first_name"=>"Federico", "last_name"=>"Canzian", "scopus_author_id"=>"56221555400"}, {"first_name"=>"Michelle", "last_name"=>"Cotterchio", "scopus_author_id"=>"6701504508"}, {"first_name"=>"Eric J.", "last_name"=>"Duell", "scopus_author_id"=>"7004300753"}, {"first_name"=>"Steve", "last_name"=>"Gallinger", "scopus_author_id"=>"34975072000"}, {"first_name"=>"Graham G.", "last_name"=>"Giles", "scopus_author_id"=>"57193910834"}, {"first_name"=>"Michael", "last_name"=>"Goggins", "scopus_author_id"=>"7005113236"}, {"first_name"=>"Phyllis J.", "last_name"=>"Goodman", "scopus_author_id"=>"7102668993"}, {"first_name"=>"Patricia", "last_name"=>"Hartge", "scopus_author_id"=>"7005897469"}, {"first_name"=>"Manal", "last_name"=>"Hassan", "scopus_author_id"=>"7401625793"}, {"first_name"=>"Kathy", "last_name"=>"Helzlsouer", "scopus_author_id"=>"7005368889"}, {"first_name"=>"Brian", "last_name"=>"Henderson", "scopus_author_id"=>"36045477600"}, {"first_name"=>"Elizabeth A.", "last_name"=>"Holly", "scopus_author_id"=>"7005548789"}, {"first_name"=>"Robert", "last_name"=>"Hoover", "scopus_author_id"=>"7202691823"}, {"first_name"=>"Eric J.", "last_name"=>"Jacobs", "scopus_author_id"=>"7201383459"}, {"first_name"=>"Aruna", "last_name"=>"Kamineni", "scopus_author_id"=>"15132358600"}, {"first_name"=>"Alison", "last_name"=>"Klein", "scopus_author_id"=>"7402143633"}, {"first_name"=>"Eric", "last_name"=>"Klein", "scopus_author_id"=>"7402149579"}, {"first_name"=>"Laurence N.", "last_name"=>"Kolonel", "scopus_author_id"=>"7005665016"}, {"first_name"=>"Donghui", "last_name"=>"Li", "scopus_author_id"=>"35290518800"}, {"first_name"=>"Núria", "last_name"=>"Malats", "scopus_author_id"=>"7003898578"}, {"first_name"=>"Satu", "last_name"=>"Männistö", "scopus_author_id"=>"6701509717"}, {"first_name"=>"Marjorie L.", "last_name"=>"McCullough", "scopus_author_id"=>"7101948683"}, {"first_name"=>"Sara H.", "last_name"=>"Olson", "scopus_author_id"=>"7202062781"}, {"first_name"=>"Irene", "last_name"=>"Orlow", "scopus_author_id"=>"6701549669"}, {"first_name"=>"Ulrike", "last_name"=>"Peters", "scopus_author_id"=>"7101680952"}, {"first_name"=>"Gloria M.", "last_name"=>"Petersen", "scopus_author_id"=>"7202922935"}, {"first_name"=>"Miquel", "last_name"=>"Porta", "scopus_author_id"=>"7102301883"}, {"first_name"=>"Gianluca", "last_name"=>"Severi", "scopus_author_id"=>"7004042887"}, {"first_name"=>"Xiao Ou", "last_name"=>"Shu", "scopus_author_id"=>"55630916600"}, {"first_name"=>"Kala", "last_name"=>"Visvanathan", "scopus_author_id"=>"7004522568"}, {"first_name"=>"Emily", "last_name"=>"White", "scopus_author_id"=>"35312877800"}, {"first_name"=>"Herbert", "last_name"=>"Yu", "scopus_author_id"=>"55653762900"}, {"first_name"=>"Anne", "last_name"=>"Zeleniuch-Jacquotte", "scopus_author_id"=>"7005250660"}, {"first_name"=>"Wei", "last_name"=>"Zheng", "scopus_author_id"=>"35381589100"}, {"first_name"=>"Geoffrey S.", "last_name"=>"Tobias", "scopus_author_id"=>"15849569800"}, {"first_name"=>"Dennis", "last_name"=>"Maeder", "scopus_author_id"=>"57189981873"}, {"first_name"=>"Michelle", "last_name"=>"Brotzman", "scopus_author_id"=>"6508020859"}, {"first_name"=>"Harvey", "last_name"=>"Risch", "scopus_author_id"=>"7006408721"}, {"first_name"=>"Joshua N.", "last_name"=>"Sampson", "scopus_author_id"=>"9733825800"}, {"first_name"=>"Rachael Z.", "last_name"=>"Stolzenberg-Solomon", "scopus_author_id"=>"6701861730"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"25799011", "doi"=>"10.1371/journal.pone.0117574", "sgr"=>"84925710772", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "scopus"=>"2-s2.0-84925710772", "issn"=>"19326203", "pui"=>"603282236"}, "id"=>"090fcb5c-37f6-3842-9234-4c42e15bbc09", "abstract"=>"Evidence on the association between vitamin D status and pancreatic cancer risk is inconsistent. This inconsistency may be partially attributable to variation in vitamin D regulating genes. We selected 11 vitamin D-related genes (GC, DHCR7, CYP2R1, VDR, CYP27B1, CYP24A1, CYP27A1, RXRA, CRP2, CASR and CUBN) totaling 213 single nucleotide polymorphisms (SNPs), and examined associations with pancreatic adenocarcinoma. Our study included 3,583 pancreatic cancer cases and 7,053 controls from the genome-wide association studies of pancreatic cancer PanScans-I-III. We used the Adaptive Joint Test and the Adaptive Rank Truncated Product statistic for pathway and gene analyses, and unconditional logistic regression for SNP analyses, adjusting for age, sex, study and population stratification. We examined effect modification by circulating vitamin D concentration (≤50, >50 nmol/L) for the most significant SNPs using a subset of cohort cases (n = 713) and controls (n = 878). The vitamin D metabolic pathway was not associated with pancreatic cancer risk (p = 0.830). Of the individual genes, none were associated with pancreatic cancer risk at a significance level of p<0.05. SNPs near the VDR (rs2239186), LRP2 (rs4668123), CYP24A1 (rs2762932), GC (rs2282679), and CUBN (rs1810205) genes were the top SNPs associated with pancreatic cancer (p-values 0.008-0.037), but none were statistically significant after adjusting for multiple comparisons. Associations between these SNPs and pancreatic cancer were not modified by circulating concentrations of vitamin D. These findings do not support an association between vitamin D-related genes and pancreatic cancer risk. Future research should explore other pathways through which vitamin D status might be associated with pancreatic cancer risk.", "link"=>"http://www.mendeley.com/research/vitamin-d-metabolic-pathway-genes-pancreatic-cancer-risk-2", "reader_count"=>20, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>4, "Researcher"=>2, "Student > Ph. D. Student"=>4, "Other"=>1, "Student > Master"=>1, "Student > Bachelor"=>6, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>4, "Researcher"=>2, "Student > Ph. D. Student"=>4, "Other"=>1, "Student > Master"=>1, "Student > Bachelor"=>6, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>6, "Medicine and Dentistry"=>3, "Agricultural and Biological Sciences"=>10, "Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>10}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>6}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "group_count"=>2}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1982140"], "description"=>"<p><sup>a</sup> After bonferroni correction (0.05/213) p-values < 0.0002 were considered significant</p><p><sup>b</sup> Odds ratios (ORs) were adjusted for age (≤50, 51–60, 61–70, 71–80, ≥81 years), sex, study, and population stratification by 5 eigenvectors for ethnic ancestry.</p><p><sup>c</sup> Odds ratios (ORs) are for the number of copies of the minor allele.</p><p><sup>d</sup> Phase refers to participation in PanScan I, II or III. For rs4668123 data was available only from PanScan phases II and III.</p><p>Vitamin-D related single nucleotide polymorphisms (SNPs) with p-values <0.05 and risk of pancreatic cancer from PanScan I-III (3,583 cases and 7,053 controls).</p>", "links"=>[], "tags"=>["Vitamin D", "2r", "gc", "CYP 27B CYP 24A CYP 27A RXRA", "association", "snp", "crp", "vdr", "Pancreatic cancer", "Pancreatic Cancer Risk Evidence", "vitamin D status", "lrp", "gene", "Adaptive Rank Truncated Product statistic", "casr", "DHCR", "Vitamin D Metabolic Pathway Genes", "CUBN", "pancreatic cancer risk", "Adaptive Joint Test"], "article_id"=>1350742, "categories"=>["Biological Sciences"], "users"=>["Hannah Arem", "Kai Yu", "Xiaoqin Xiong", "Kristin Moy", "Neal D. Freedman", "Susan T. Mayne", "Demetrius Albanes", "Alan A. Arslan", "Melissa Austin", "William R. Bamlet", "Laura Beane-Freeman", "Paige Bracci", "Federico Canzian", "Michelle Cotterchio", "Eric J. Duell", "Steve Gallinger", "Graham G. Giles", "Michael Goggins", "Phyllis J. Goodman", "Patricia Hartge", "Manal Hassan", "Kathy Helzlsouer", "Brian Henderson", "Elizabeth A. Holly", "Robert Hoover", "Eric J. Jacobs", "Aruna Kamineni", "Alison Klein", "Eric Klein", "Laurence N. Kolonel", "Donghui Li", "Núria Malats", "Satu Männistö", "Marjorie L. McCullough", "Sara H. Olson", "Irene Orlow", "Ulrike Peters", "Gloria M. Petersen", "Miquel Porta", "Gianluca Severi", "Xiao-Ou Shu", "Kala Visvanathan", "Emily White", "Herbert Yu", "Anne Zeleniuch-Jacquotte", "Wei Zheng", "Geoffrey S. Tobias", "Dennis Maeder", "Michelle Brotzman", "Harvey Risch", "Joshua N. Sampson", "Rachael Z. Stolzenberg-Solomon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0117574.t002", "stats"=>{"downloads"=>4, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Vitamin_D_related_single_nucleotide_polymorphisms_SNPs_with_p_values_lt_0_05_and_risk_of_pancreatic_cancer_from_PanScan_I_III_3_583_cases_and_7_053_controls_/1350742", "title"=>"Vitamin-D related single nucleotide polymorphisms (SNPs) with p-values <0.05 and risk of pancreatic cancer from PanScan I-III (3,583 cases and 7,053 controls).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-03-23 04:46:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1982138"], "description"=>"<p><sup>a</sup>P-values account for number of SNPs within genes or within the overall pathway, but not for the total number of genes; Models were adjusted for age (≤50, 51–60, 61–70, 71–80, ≥81 years), sex, study and population stratification by 5 eigenvectors for ethnic ancestry.</p><p>Pathway analysis for risk of pancreatic cancer and gene sets in the vitamin D pathway (3,583 cases and 7,053 controls)</p>", "links"=>[], "tags"=>["Vitamin D", "2r", "gc", "CYP 27B CYP 24A CYP 27A RXRA", "association", "snp", "crp", "vdr", "Pancreatic cancer", "Pancreatic Cancer Risk Evidence", "vitamin D status", "lrp", "gene", "Adaptive Rank Truncated Product statistic", "casr", "DHCR", "Vitamin D Metabolic Pathway Genes", "CUBN", "pancreatic cancer risk", "Adaptive Joint Test"], "article_id"=>1350740, "categories"=>["Biological Sciences"], "users"=>["Hannah Arem", "Kai Yu", "Xiaoqin Xiong", "Kristin Moy", "Neal D. Freedman", "Susan T. Mayne", "Demetrius Albanes", "Alan A. Arslan", "Melissa Austin", "William R. Bamlet", "Laura Beane-Freeman", "Paige Bracci", "Federico Canzian", "Michelle Cotterchio", "Eric J. Duell", "Steve Gallinger", "Graham G. Giles", "Michael Goggins", "Phyllis J. Goodman", "Patricia Hartge", "Manal Hassan", "Kathy Helzlsouer", "Brian Henderson", "Elizabeth A. Holly", "Robert Hoover", "Eric J. Jacobs", "Aruna Kamineni", "Alison Klein", "Eric Klein", "Laurence N. Kolonel", "Donghui Li", "Núria Malats", "Satu Männistö", "Marjorie L. McCullough", "Sara H. Olson", "Irene Orlow", "Ulrike Peters", "Gloria M. Petersen", "Miquel Porta", "Gianluca Severi", "Xiao-Ou Shu", "Kala Visvanathan", "Emily White", "Herbert Yu", "Anne Zeleniuch-Jacquotte", "Wei Zheng", "Geoffrey S. Tobias", "Dennis Maeder", "Michelle Brotzman", "Harvey Risch", "Joshua N. Sampson", "Rachael Z. Stolzenberg-Solomon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0117574.t001", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pathway_analysis_for_risk_of_pancreatic_cancer_and_gene_sets_in_the_vitamin_D_pathway_3_583_cases_and_7_053_controls_/1350740", "title"=>"Pathway analysis for risk of pancreatic cancer and gene sets in the vitamin D pathway (3,583 cases and 7,053 controls)", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-03-23 04:46:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1982141", "https://ndownloader.figshare.com/files/1982142", "https://ndownloader.figshare.com/files/1982143", "https://ndownloader.figshare.com/files/1982144", "https://ndownloader.figshare.com/files/1982145"], "description"=>"<div><p>Evidence on the association between vitamin D status and pancreatic cancer risk is inconsistent. This inconsistency may be partially attributable to variation in vitamin D regulating genes. We selected 11 vitamin D-related genes (<i>GC</i>, <i>DHCR7</i>, <i>CYP2R1</i>, <i>VDR</i>, <i>CYP27B1</i>, <i>CYP24A1</i>, <i>CYP27A1</i>, <i>RXRA</i>, <i>CRP2</i>, <i>CASR</i> and <i>CUBN</i>) totaling 213 single nucleotide polymorphisms (SNPs), and examined associations with pancreatic adenocarcinoma. Our study included 3,583 pancreatic cancer cases and 7,053 controls from the genome-wide association studies of pancreatic cancer PanScans-I-III. We used the Adaptive Joint Test and the Adaptive Rank Truncated Product statistic for pathway and gene analyses, and unconditional logistic regression for SNP analyses, adjusting for age, sex, study and population stratification. We examined effect modification by circulating vitamin D concentration (≤50, >50 nmol/L) for the most significant SNPs using a subset of cohort cases (n = 713) and controls (n = 878). The vitamin D metabolic pathway was not associated with pancreatic cancer risk (p = 0.830). Of the individual genes, none were associated with pancreatic cancer risk at a significance level of p<0.05. SNPs near the <i>VDR</i> (rs2239186), <i>LRP2</i> (rs4668123), <i>CYP24A1</i> (rs2762932), <i>GC</i> (rs2282679), and <i>CUBN</i> (rs1810205) genes were the top SNPs associated with pancreatic cancer (p-values 0.008–0.037), but none were statistically significant after adjusting for multiple comparisons. Associations between these SNPs and pancreatic cancer were not modified by circulating concentrations of vitamin D. These findings do not support an association between vitamin D-related genes and pancreatic cancer risk. Future research should explore other pathways through which vitamin D status might be associated with pancreatic cancer risk.</p></div>", "links"=>[], "tags"=>["Vitamin D", "2r", "gc", "CYP 27B CYP 24A CYP 27A RXRA", "association", "snp", "crp", "vdr", "Pancreatic cancer", "Pancreatic Cancer Risk Evidence", "vitamin D status", "lrp", "gene", "Adaptive Rank Truncated Product statistic", "casr", "DHCR", "Vitamin D Metabolic Pathway Genes", "CUBN", "pancreatic cancer risk", "Adaptive Joint Test"], "article_id"=>1350743, "categories"=>["Biological Sciences"], "users"=>["Hannah Arem", "Kai Yu", "Xiaoqin Xiong", "Kristin Moy", "Neal D. Freedman", "Susan T. Mayne", "Demetrius Albanes", "Alan A. Arslan", "Melissa Austin", "William R. Bamlet", "Laura Beane-Freeman", "Paige Bracci", "Federico Canzian", "Michelle Cotterchio", "Eric J. Duell", "Steve Gallinger", "Graham G. Giles", "Michael Goggins", "Phyllis J. Goodman", "Patricia Hartge", "Manal Hassan", "Kathy Helzlsouer", "Brian Henderson", "Elizabeth A. Holly", "Robert Hoover", "Eric J. Jacobs", "Aruna Kamineni", "Alison Klein", "Eric Klein", "Laurence N. Kolonel", "Donghui Li", "Núria Malats", "Satu Männistö", "Marjorie L. McCullough", "Sara H. Olson", "Irene Orlow", "Ulrike Peters", "Gloria M. Petersen", "Miquel Porta", "Gianluca Severi", "Xiao-Ou Shu", "Kala Visvanathan", "Emily White", "Herbert Yu", "Anne Zeleniuch-Jacquotte", "Wei Zheng", "Geoffrey S. Tobias", "Dennis Maeder", "Michelle Brotzman", "Harvey Risch", "Joshua N. Sampson", "Rachael Z. Stolzenberg-Solomon"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0117574.s001", "https://dx.doi.org/10.1371/journal.pone.0117574.s002", "https://dx.doi.org/10.1371/journal.pone.0117574.s003", "https://dx.doi.org/10.1371/journal.pone.0117574.s004", "https://dx.doi.org/10.1371/journal.pone.0117574.s005"], "stats"=>{"downloads"=>3, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Vitamin_D_Metabolic_Pathway_Genes_and_Pancreatic_Cancer_Risk_/1350743", "title"=>"Vitamin D Metabolic Pathway Genes and Pancreatic Cancer Risk", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-03-23 04:46:56"}

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  • {"unique-ip"=>"16", "full-text"=>"16", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}
  • {"unique-ip"=>"7", "full-text"=>"4", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}
  • {"unique-ip"=>"13", "full-text"=>"13", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"2"}
  • {"unique-ip"=>"15", "full-text"=>"14", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"10", "cited-by"=>"0", "year"=>"2020", "month"=>"3"}
  • {"unique-ip"=>"9", "full-text"=>"7", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2020", "month"=>"4"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2020", "month"=>"5"}
  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"6"}
  • {"unique-ip"=>"20", "full-text"=>"8", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"31", "year"=>"2020", "month"=>"7"}
  • {"unique-ip"=>"16", "full-text"=>"7", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"9", "cited-by"=>"12", "year"=>"2020", "month"=>"8"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2020", "month"=>"9"}

Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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