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

doi:10.1007/s10552-012-0138-0

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 KooperbergAndrea 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

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

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.

Original language	English (US)
Pages (from-to)	595-602
Number of pages	8
Journal	Cancer Causes and Control
Volume	24
Issue number	3
DOIs	https://doi.org/10.1007/s10552-012-0138-0
State	Published - Mar 2013

Keywords

Biomarkers
Epidemiology
One-carbon metabolism
Pancreatic cancer
Polymorphisms

ASJC Scopus subject areas

Oncology
Cancer Research

Access to Document

10.1007/s10552-012-0138-0

Cite this

Leenders, M., Bhattacharjee, S., Vineis, P., Stevens, V., Bueno-De-Mesquita, H. B., Shu, X. O., Amundadottir, L., Gross, M., Tobias, G. S., Wactawski-Wende, J., Arslan, A. A., Duell, E. J., Fuchs, C. S., Gallinger, S., Hartge, P., Hoover, R. N., Holly, E. A., Jacobs, E. J., Klein, A. P., ... Stolzenberg-Solomon, R. Z. (2013). Polymorphisms in genes related to one-carbon metabolism are not related to pancreatic cancer in PanScan and PanC4. Cancer Causes and Control, 24(3), 595-602. https://doi.org/10.1007/s10552-012-0138-0

Leenders, M, Bhattacharjee, S, Vineis, P, Stevens, V, Bueno-De-Mesquita, HB, Shu, XO, Amundadottir, L, Gross, M, Tobias, GS, Wactawski-Wende, J, Arslan, AA, Duell, EJ, Fuchs, CS, Gallinger, S, Hartge, P, Hoover, RN, Holly, EA, Jacobs, EJ, Klein, AP, Kooperberg, C, Lacroix, A, Li, D, Mandelson, MT, Olson, SH, Petersen, G, Risch, HA, Yu, K, Wolpin, BM, Zheng, W, Agalliu, I, Albanes, D, Boutron-Ruault, MC, Bracci, PM, Buring, JE, Canzian, F, Chang, K, Chanock, SJ, Cotterchio, M, Gaziano, JM, Giovanucci, EL, Goggins, M, Hallmans, G, Hankinson, SE, Hoffman-Bolton, JA, Hunter, DJ, Hutchinson, A, Jacobs, KB, Jenab, M, Khaw, KT, Kraft, P, Krogh, V, Kurtz, RC, McWilliams, RR, Mendelsohn, JB, Patel, AV, Rabe, KG, Riboli, E, Tjønneland, A, Trichopoulos, D, Virtamo, J, Visvanathan, K, Elena, JW, Yu, H, Zeleniuch-Jacquotte, A & Stolzenberg-Solomon, RZ 2013, 'Polymorphisms in genes related to one-carbon metabolism are not related to pancreatic cancer in PanScan and PanC4', Cancer Causes and Control, vol. 24, no. 3, pp. 595-602. https://doi.org/10.1007/s10552-012-0138-0

@article{3e85805ff5f44346af18916f7f835ba0,

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

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 = "Biomarkers, Epidemiology, One-carbon metabolism, Pancreatic cancer, Polymorphisms",

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

note = "Funding Information: The gene-level results using the Adaptive Rank Truncated Product approach, of the 37 genes in a total of 1,407 pancreatic cancer cases and 1,463 controls. For each SNP, the logistic regression analysis used adjustment for age in 10-year categories, sex, study, five principal components of population stratification. Adjustment for multiple comparisons was done using an FDR correction for the cohort and combined stage, and using a Bonferroni correction for the case– control stage a Gene neighborhood within 20 kb upstream and 10 kb downstream of SNP b Chromosome and NCBI Human genome Build 36 location c Subset: cohort, cohort studies; replication, case–control, case–control studies; combined, all studies Acknowledgments This research was supported by the Intramural Research Program of the National Institutes of Health, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services. This study has been funded by the World Cancer Research Fund (Grant No. 2008/51 to PV). For full acknowledgments, please see electronic supplementary material.",

year = "2013",

month = mar,

doi = "10.1007/s10552-012-0138-0",

language = "English (US)",

volume = "24",

pages = "595--602",

journal = "Cancer Causes and Control",

issn = "0957-5243",

publisher = "Springer Netherlands",

number = "3",

}

TY - JOUR

T1 - Polymorphisms in genes related to one-carbon metabolism are not related to pancreatic cancer in PanScan and PanC4

AU - Leenders, Max

AU - Bhattacharjee, Samsiddhi

AU - Vineis, Paolo

AU - Stevens, Victoria

AU - Bueno-De-Mesquita, H. Bas

AU - Shu, Xiao Ou

AU - Amundadottir, Laufey

AU - Gross, Myron

AU - Tobias, Geoffrey S.

AU - Wactawski-Wende, Jean

AU - Arslan, Alan A.

AU - Duell, Eric J.

AU - Fuchs, Charles S.

AU - Gallinger, Steven

AU - Hartge, Patricia

AU - Hoover, Robert N.

AU - Holly, Elizabeth A.

AU - Jacobs, Eric J.

AU - Klein, Alison P.

AU - Kooperberg, Charles

AU - Lacroix, Andrea

AU - Li, Donghui

AU - Mandelson, Margaret T.

AU - Olson, Sara H.

AU - Petersen, Gloria

AU - Risch, Harvey A.

AU - Yu, Kai

AU - Wolpin, Brian M.

AU - Zheng, Wei

AU - Agalliu, Ilir

AU - Albanes, Demetrius

AU - Boutron-Ruault, Marie Christine

AU - Bracci, Paige M.

AU - Buring, Julie E.

AU - Canzian, Federico

AU - Chang, Kenneth

AU - Chanock, Stephen J.

AU - Cotterchio, Michelle

AU - Gaziano, J. Michael

AU - Giovanucci, Edward L.

AU - Goggins, Michael

AU - Hallmans, Göran

AU - Hankinson, Susan E.

AU - Hoffman-Bolton, Judith A.

AU - Hunter, David J.

AU - Hutchinson, Amy

AU - Jacobs, Kevin B.

AU - Jenab, Mazda

AU - Khaw, Kay Tee

AU - Kraft, Peter

AU - Krogh, Vittorio

AU - Kurtz, Robert C.

AU - McWilliams, Robert R.

AU - Mendelsohn, Julie B.

AU - Patel, Alpa V.

AU - Rabe, Kari G.

AU - Riboli, Elio

AU - Tjønneland, Anne

AU - Trichopoulos, Dimitrios

AU - Virtamo, Jarmo

AU - Visvanathan, Kala

AU - Elena, Joanne W.

AU - Yu, Herbert

AU - Zeleniuch-Jacquotte, Anne

AU - Stolzenberg-Solomon, Rachael Z.

N1 - Funding Information: The gene-level results using the Adaptive Rank Truncated Product approach, of the 37 genes in a total of 1,407 pancreatic cancer cases and 1,463 controls. For each SNP, the logistic regression analysis used adjustment for age in 10-year categories, sex, study, five principal components of population stratification. Adjustment for multiple comparisons was done using an FDR correction for the cohort and combined stage, and using a Bonferroni correction for the case– control stage a Gene neighborhood within 20 kb upstream and 10 kb downstream of SNP b Chromosome and NCBI Human genome Build 36 location c Subset: cohort, cohort studies; replication, case–control, case–control studies; combined, all studies Acknowledgments This research was supported by the Intramural Research Program of the National Institutes of Health, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services. This study has been funded by the World Cancer Research Fund (Grant No. 2008/51 to PV). For full acknowledgments, please see electronic supplementary material.

PY - 2013/3

Y1 - 2013/3

N2 - 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.

AB - 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.

KW - Biomarkers

KW - Epidemiology

KW - One-carbon metabolism

KW - Pancreatic cancer

KW - Polymorphisms

UR - http://www.scopus.com/inward/record.url?scp=84878889004&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878889004&partnerID=8YFLogxK

U2 - 10.1007/s10552-012-0138-0

DO - 10.1007/s10552-012-0138-0

M3 - Article

C2 - 23334854

AN - SCOPUS:84878889004

SN - 0957-5243

VL - 24

SP - 595

EP - 602

JO - Cancer Causes and Control

JF - Cancer Causes and Control

IS - 3

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this