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Title: Gene-nutrient interactions among determinants of folate and one-carbon metabolism on the risk of non-Hodgkin lymphoma: NCI-SEER Case-Control Study.
Author: Lim U, Wang SS, Hartge P, Cozen W, Kelemen LE, Chanock S, Davis S, Blair A, Schenk M, Rothman N, Lan Q
Journal: Blood 109(7):3050-3059
Year: 2007
Month: April

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 1,141 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 (OR) and 95% confidence intervals (CI) were adjusted for age, gender, 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.