Gene-nutrient interactions among determinants of folate and one-carbon metabolism on the risk of non-Hodgkin lymphoma: NCI-SEER case-control study

Unhee Lim, Sophia S. Wang, Patricia Hartge, Wendy Cozen, Linda E. Kelemen, Stephen Chanock, Scott Davis, Aaron Blair, Maryjean Schenk, Nathaniel Rothman, Qing Lan

Research output: Contribution to journalArticle

Abstract

We previously reported a lower risk of non-Hodgkin lymphoma (NHL) associated with high consumption of vitamin B6 and methionine, dietary determinants of one-carbon metabolism. Evidence has linked genetic variants involved in one-carbon metabolism to NHL. We investigated 30 polymorphisms in 18 genes for their main effect on NHL among 1141 incident cases and 949 population-based controls and examined gene-nutrient interactions in a subgroup of 386 cases and 319 controls who provided detailed food-frequency information. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for age, sex, and race. We observed a decreased risk of NHL overall with BHMT Ex8+453A>T and increased risk with CBS Ex13+41C>T, FPGS Ex15-263T>C, and SHMT1 Ex12+138C>T and Ex12+236C>T. Furthermore, significant gene-nutrient interactions limited the protective association comparing high versus low vitamin B6 to FPGS Ex15-263T>C CC (OR = 0.22; 95% CI = 0.10-0.52), MTHFS IVS2-1411T>G TT/TG (OR = 0.54; 95% CI = 0.36-0.81), and MTR Ex26-20A>G AA (OR = 0.55; 95% CI = 0.35-0.86) genotypes, and the protective association of methionine to FTHFD Ex10-40G>T GG (OR = 0.63; 95% CI = 0.44-0.91), MTHFR Ex8-62A>CCC (OR = 0.13; 95% CI = 0.04-0.39), and MTRR Ex5+136T>CTT(OR = 0.67;95%CI = 0.47-0.97) genotypes. Warranting replication, our finding of gene-nutrient interactions in onecarbon metabolism supports their etiologic involvement in lymphomagenesis.

Original languageEnglish (US)
Pages (from-to)3050-3059
Number of pages10
JournalBlood
Volume109
Issue number7
DOIs
StatePublished - Apr 1 2007

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Lim, U., Wang, S. S., Hartge, P., Cozen, W., Kelemen, L. E., Chanock, S., Davis, S., Blair, A., Schenk, M., Rothman, N., & Lan, Q. (2007). Gene-nutrient interactions among determinants of folate and one-carbon metabolism on the risk of non-Hodgkin lymphoma: NCI-SEER case-control study. Blood, 109(7), 3050-3059. https://doi.org/10.1182/blood-2006-07-034330