Cancer Causes & Control

, Volume 24, Issue 3, pp 595–602

Polymorphisms in genes related to one-carbon metabolism are not related to pancreatic cancer in PanScan and PanC4

  • Max Leenders
  • Samsiddhi Bhattacharjee
  • Paolo Vineis
  • Victoria Stevens
  • H. Bas Bueno-de-Mesquita
  • Xiao-Ou Shu
  • Laufey Amundadottir
  • Myron Gross
  • Geoffrey S. Tobias
  • Jean Wactawski-Wende
  • Alan A. Arslan
  • Eric J. Duell
  • Charles S. Fuchs
  • Steven Gallinger
  • Patricia Hartge
  • Robert N. Hoover
  • Elizabeth A. Holly
  • Eric J. Jacobs
  • Alison P. Klein
  • Charles Kooperberg
  • Andrea LaCroix
  • Donghui Li
  • Margaret T. Mandelson
  • Sara H. Olson
  • Gloria Petersen
  • Harvey A. Risch
  • Kai Yu
  • Brian M. Wolpin
  • Wei Zheng
  • Ilir Agalliu
  • Demetrius Albanes
  • Marie-Christine Boutron-Ruault
  • Paige M. Bracci
  • Julie E. Buring
  • Federico Canzian
  • Kenneth Chang
  • Stephen J. Chanock
  • Michelle Cotterchio
  • J. Michael Gaziano
  • Edward L. Giovanucci
  • Michael Goggins
  • Göran Hallmans
  • Susan E. Hankinson
  • Judith A. Hoffman-Bolton
  • David J. Hunter
  • Amy Hutchinson
  • Kevin B. Jacobs
  • Mazda Jenab
  • Kay-Tee Khaw
  • Peter Kraft
  • Vittorio Krogh
  • Robert C. Kurtz
  • Robert R. McWilliams
  • Julie B. Mendelsohn
  • Alpa V. Patel
  • Kari G. Rabe
  • Elio Riboli
  • Anne Tjønneland
  • Dimitrios Trichopoulos
  • Jarmo Virtamo
  • Kala Visvanathan
  • Joanne W. Elena
  • Herbert Yu
  • Anne Zeleniuch-Jacquotte
  • Rachael Z. Stolzenberg-Solomon
Brief report

DOI: 10.1007/s10552-012-0138-0

Cite this article as:
Leenders, M., Bhattacharjee, S., Vineis, P. et al. Cancer Causes Control (2013) 24: 595. doi:10.1007/s10552-012-0138-0

Abstract

Purpose

The evidence of a relation between folate intake and one-carbon metabolism (OCM) with pancreatic cancer (PanCa) is inconsistent. In this study, the association between genes and single-nucleotide polymorphisms (SNPs) related to OCM and PanCa was assessed.

Methods

Using biochemical knowledge of the OCM pathway, we identified thirty-seven genes and 834 SNPs to examine in association with PanCa. Our study included 1,408 cases and 1,463 controls nested within twelve cohorts (PanScan). The ten SNPs and five genes with lowest p values (<0.02) were followed up in 2,323 cases and 2,340 controls from eight case–control studies (PanC4) that participated in PanScan2. The correlation of SNPs with metabolite levels was assessed for 649 controls from the European Prospective Investigation into Cancer and Nutrition.

Results

When both stages were combined, we observed suggestive associations with PanCa for rs10887710 (MAT1A) (OR 1.13, 95 %CI 1.04–1.23), rs1552462 (SYT9) (OR 1.27, 95 %CI 1.02–1.59), and rs7074891 (CUBN) (OR 1.91, 95 %CI 1.12–3.26). After correcting for multiple comparisons, no significant associations were observed in either the first or second stage. The three suggested SNPs showed no correlations with one-carbon biomarkers.

Conclusions

This is the largest genetic study to date to examine the relation between germline variations in OCM-related genes polymorphisms and the risk of PanCa. Suggestive evidence for an association between polymorphisms and PanCa was observed among the cohort-nested studies, but this did not replicate in the case–control studies. Our results do not strongly support the hypothesis that genes related to OCM play a role in pancreatic carcinogenesis.

Keywords

Pancreatic cancer One-carbon metabolism Polymorphisms Biomarkers Epidemiology 

Supplementary material

10552_2012_138_MOESM1_ESM.docx (16 kb)
Supplementary material 1 (DOCX 16 kb)

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Max Leenders
    • 1
    • 2
  • Samsiddhi Bhattacharjee
    • 3
  • Paolo Vineis
    • 1
    • 4
  • Victoria Stevens
    • 5
  • H. Bas Bueno-de-Mesquita
    • 2
    • 6
  • Xiao-Ou Shu
    • 7
  • Laufey Amundadottir
    • 3
    • 8
  • Myron Gross
    • 9
  • Geoffrey S. Tobias
    • 3
  • Jean Wactawski-Wende
    • 10
  • Alan A. Arslan
    • 11
    • 12
    • 13
  • Eric J. Duell
    • 14
  • Charles S. Fuchs
    • 15
    • 16
  • Steven Gallinger
    • 17
  • Patricia Hartge
    • 3
  • Robert N. Hoover
    • 3
  • Elizabeth A. Holly
    • 18
  • Eric J. Jacobs
    • 19
  • Alison P. Klein
    • 20
    • 21
  • Charles Kooperberg
    • 22
  • Andrea LaCroix
    • 5
  • Donghui Li
    • 23
  • Margaret T. Mandelson
    • 22
    • 24
  • Sara H. Olson
    • 25
  • Gloria Petersen
    • 26
  • Harvey A. Risch
    • 27
  • Kai Yu
    • 3
  • Brian M. Wolpin
    • 15
    • 16
  • Wei Zheng
    • 7
  • Ilir Agalliu
    • 28
  • Demetrius Albanes
    • 3
  • Marie-Christine Boutron-Ruault
    • 29
  • Paige M. Bracci
    • 18
  • Julie E. Buring
    • 30
    • 31
  • Federico Canzian
    • 32
  • Kenneth Chang
    • 33
  • Stephen J. Chanock
    • 3
    • 8
  • Michelle Cotterchio
    • 34
    • 35
  • J. Michael Gaziano
    • 36
    • 37
  • Edward L. Giovanucci
    • 16
    • 38
    • 39
  • Michael Goggins
    • 40
  • Göran Hallmans
    • 41
  • Susan E. Hankinson
    • 16
    • 38
  • Judith A. Hoffman-Bolton
    • 42
  • David J. Hunter
    • 16
    • 38
  • Amy Hutchinson
    • 3
    • 43
  • Kevin B. Jacobs
    • 3
    • 43
    • 44
  • Mazda Jenab
    • 45
  • Kay-Tee Khaw
    • 46
  • Peter Kraft
    • 38
    • 47
  • Vittorio Krogh
    • 48
  • Robert C. Kurtz
    • 49
  • Robert R. McWilliams
    • 50
  • Julie B. Mendelsohn
    • 3
  • Alpa V. Patel
    • 5
  • Kari G. Rabe
    • 26
  • Elio Riboli
    • 1
  • Anne Tjønneland
    • 51
  • Dimitrios Trichopoulos
    • 38
    • 52
  • Jarmo Virtamo
    • 53
  • Kala Visvanathan
    • 42
  • Joanne W. Elena
    • 54
  • Herbert Yu
    • 27
  • Anne Zeleniuch-Jacquotte
    • 12
    • 13
  • Rachael Z. Stolzenberg-Solomon
    • 3
  1. 1.Department of Epidemiology and Biostatistics, School of Public HealthImperial CollegeLondonUK
  2. 2.Department of Gastroenterology and HepatologyUniversity Medical Center UtrechtUtrechtThe Netherlands
  3. 3.Division of Cancer Epidemiology and GeneticsNational Cancer Institute, National Institutes of HealthBethesdaUSA
  4. 4.HuGeF FoundationTurinItaly
  5. 5.Department of EpidemiologyAmerican Cancer SocietyAtlantaUSA
  6. 6.National Institute for Public Health and the EnvironmentBilthovenThe Netherlands
  7. 7.Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer CenterVanderbilt UniversityNashvilleUSA
  8. 8.Laboratory of Translational Genomics, Division of Cancer Epidemiology and GeneticsNational Cancer Institute, National Institutes of HealthBethesdaUSA
  9. 9.Department of Laboratory Medicine/Pathology, School of MedicineUniversity of MinnesotaMinneapolisUSA
  10. 10.Department of Social and Preventive MedicineUniversity at Buffalo, State University of New YorkBuffaloUSA
  11. 11.Department of Obstetrics and GynecologyNew York University School of MedicineNew YorkUSA
  12. 12.Department of Environmental MedicineNew York University School of MedicineNew YorkUSA
  13. 13.New York University Cancer InstituteNew YorkUSA
  14. 14.Catalan Institute of Oncology (ICO-IDIBELL)BarcelonaSpain
  15. 15.Department of Medical OncologyDana-Farber Cancer InstituteBostonUSA
  16. 16.Channing Laboratory, Department of MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA
  17. 17.Samuel Lunenfeld Research Institute, Mount Sinai HospitalUniversity of TorontoTorontoCanada
  18. 18.Department of Epidemiology and BiostatisticsUniversity of California San FranciscoSan FranciscoUSA
  19. 19.Epidemiology Research ProgramAmerican Cancer SocietyAtlantaUSA
  20. 20.Department of OncologyJohns Hopkins University School of MedicineBaltimoreUSA
  21. 21.Department of Epidemiology, Johns Hopkins Medical Institutions, The Bloomberg School of Public HeathThe Sol Goldman Pancreatic Research CenterBaltimoreUSA
  22. 22.Division of Public Health SciencesFred Hutchinson Cancer Research CenterSeattleUSA
  23. 23.Department of Gastrointestinal Medical OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  24. 24.Group Health Center for Health StudiesSeattleUSA
  25. 25.Department of Epidemiology and BiostatisticsMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  26. 26.Department of Health Sciences ResearchMayo ClinicRochesterUSA
  27. 27.Yale University School of Public HealthNew HavenUSA
  28. 28.Department of Epidemiology and Population HealthAlbert Einstein College of MedicineBronxUSA
  29. 29.INSERM, Institut Gustave-RoussyParis-Sud UniversityVillejuifFrance
  30. 30.Divisions of Preventive Medicine and Aging, Department of MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA
  31. 31.Department of Ambulatory Care and PreventionHarvard Medical SchoolBostonUSA
  32. 32.Division of Cancer EpidemiologyGerman Cancer Research Center (DFKZ)HeidelbergGermany
  33. 33.Comprehensive Digestive Disease CenterUniversity of California, Irvine Medical CenterOrangeUSA
  34. 34.Dalla Lana School of Public HealthUniversity of TorontoTorontoCanada
  35. 35.Prevention and Cancer Control, Cancer Care OntarioTorontoCanada
  36. 36.Physicians’ Health Study, Divisions of Aging, Cardiovascular Medicine, and Preventive Medicine, Department of MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA
  37. 37.Veterans Affairs Boston Healthcare SystemMassachusetts Veterans Epidemiology Research and Information CenterBostonUSA
  38. 38.Department of EpidemiologyHarvard School of Public HealthBostonUSA
  39. 39.Department of NutritionHarvard School of Public HealthBostonUSA
  40. 40.Departments of Oncology, Pathology and MedicineJohns Hopkins University School of MedicineBaltimoreUSA
  41. 41.Department of Public Health and Clinical Medicine, Nutritional ResearchUmeå UniversityUmeåSweden
  42. 42.Department of Epidemiology, The Bloomberg School of Public HealthJohns Hopkins UniversityBaltimoreUSA
  43. 43.Core Genotyping Facility, Advanced Technology ProgramSAIC-Frederick Inc., NCI-FrederickFrederickUSA
  44. 44.Bioinformed Consulting ServicesGaithersburgUSA
  45. 45.International Agency for Research on Cancer (IARC/WHO)LyonFrance
  46. 46.Department of Public Health and Primary Care, Clinical Gerontology, Addenbrooke’s HospitalUniversity of CambridgeCambridgeUK
  47. 47.Department of BiostatisticsHarvard School of Public HealthBostonUSA
  48. 48.Nutritional Epidemiology UnitFondazione Istituto di Recovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei TumoriMilanItaly
  49. 49.Department of MedicineMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  50. 50.Division of Medical OncologyMayo ClinicRochesterUSA
  51. 51.Institute of Cancer EpidemiologyDanish Cancer SocietyCopenhagenDenmark
  52. 52.Bureau of Epidemiologic ResearchAcademy of AthensAthensGreece
  53. 53.Department of Chronic Disease PreventionNational Institute for Health and WelfareHelsinkiFinland
  54. 54.Division of Cancer Prevention and Population Control, Department of Health and Human ServicesNational Cancer Institute, National Institutes of HealthBethesdaUSA

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