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Blood, 1 April 2007, Vol. 109, No. 7, pp. 3050-3059. Prepublished online as a Blood First Edition Paper on November 21, 2006; DOI 10.1182/blood-2006-07-034330.
NEOPLASIA Gene-nutrient interactions among determinants of folate and one-carbon metabolism on the risk of non-Hodgkin lymphoma: NCI-SEER Case-Control Study1 Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Rockville, MD; 2 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles; 3 Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN; 4 Core Genotyping Facility, Advanced Technology Center, Division of Cancer Epidemiology and Genetics and Pediatric Oncology Branch, Center for Cancer Research, NCI, NIH, DHHS, Bethesda, MD; 5 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center and Department of Epidemiology, University of Washington, Seattle; 6 Department of Family Medicine, Wayne State University and Karmanos Cancer Institute, Detroit, MI 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>C CC (OR = 0.13; 95% CI = 0.04-0.39), and MTRR Ex5+136T>C TT (OR = 0.67; 95% CI = 0.47-0.97) genotypes. Warranting replication, our finding of gene-nutrient interactions in one-carbon metabolism supports their etiologic involvement in lymphomagenesis.
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