Study
PLCO
(Learn more about this study)
Project ID
2005-0025
Initial CDAS Request Approval
Apr 21, 2006
Title
Biomarkers and genetic polymorphisms of one-carbon metabolism and risk of lymphoid cancers
Summary
Lymphoid cancers, including non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia, and multiple myeloma, together rank fifth in U.S. cancer incidence (2). Their etiology is mostly unknown other than a few established factors of immunologic, viral, and chemical origin (3). Recent studies of genetic polymorphisms (4-8), including our own (Lim et al. in preparation), have suggested that one-carbon metabolism may be involved in lymphoma etiology, potentially through its essential role in DNA methylation and synthesis/repair (9). In support of this hypothesis, we have observed associations between nutritional determinants of one-carbon metabolism and NHL: dietary folate (OR for diffuse lymphoma=0.47; 95% CI: 0.23, 0.94) and vitamin B6 (OR=0.57; 95% CI: 0.34, 0.95) in the NCI-SEER case-control study (10) and vitamin B12 (OR=0.54; 95% CI: 0.31, 0.95) in the ATBC Study cohort (Lim et al. in preparation). We propose a nested case-control study of serum markers of one-carbon-related nutrients and genetic polymorphisms in the metabolic pathway in relation to lymphoid cancers in PLCO. In addition, we will examine DNA methylation and stability, biomarkers of a proposed mediating mechanism. PLCO provides a unique opportunity to examine the entire causal pathway involving one-carbon metabolism and lymphoma, given that it offers pre-diagnostic dietary data, peripheral blood samples for serology, and constitutional DNA for molecular phenotypes as well as genetic susceptibility. This study, along with the on-going studies in the ATBC Study cohort, will be the first prospective investigation of one-carbon metabolism biomarkers. We will combine the two studies in order to increase statistical power and to achieve a wider range of one-carbon exposure status. Further, we supplement the proposal with a pilot study, included here, that will evaluate and validate the one-carbon serum/DNA biomarkers and estimate the effect of the US nation-wide folate fortification on these markers.
Aims
Investigate the association between baseline serum levels of the one-carbon-related nutrients, folate and vitamins B12 and B6, and lymphoid cancer risk. Determine the relationship between baseline DNA markers of genomic methylation and stability and lymphoid cancer risk. Examine genetic polymorphisms in one-carbon metabolism pathway in relation to lymphoid cancer risk. Evaluate the interrelationships among dietary one-carbon nutrients, serum nutrient status, genetic polymorphisms, and the phenotypic markers of DNA methylation and stability. Assess potential effect modification by genetic polymorphisms on the relation between dietary/serum indicators of one-carbon-related nutrition and lymphoid cancers
Collaborators
Demetrius Albanes (NCI, DCEG)
Dalsu Baris (NCI, DCEG)
Barry Graubard (NCI, DCEG)
Richard Hayes (NCI, DCEG)
Wen-Hi Huang (NCI, DCEG)
Unhee Lim (NCI, DCEG)
Lindsay Morton (NCI, DCEG)
Qing Lan (NCI, DCEG)
Nathaniel Rothman (NCI, DCEG)
Sang Woon Choi (Tufts University)
Athur Schatzkin (NCI, DCEG)
Rachael Stolzenberg-Solomon (NCI, DCEG)
