Gene-nutrient interactions among determinants of folate and one-carbon metabolism on the risk of non-Hodgkin lymphoma: NCI-SEER case-control study.
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 over-all with BHMTEx8+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% CL = 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>TGG (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>CTT (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.
Lim
Unhee
U
Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Rockville, MD 20852, USA. limu@mail.nih.gov
Wang
Sophia S
SS
Hartge
Patricia
P
Cozen
Wendy
W
Kelemen
Linda E
LE
Chanock
Stephen
S
Davis
Scott
S
Blair
Aaron
A
Schenk
Maryjean
M
Rothman
Nathaniel
N
Lan
Qing
Q
D000328:Adult; D000368:Aged; D002244:Carbon / Q000378:metabolism; D016022:Case-Control Studies; D004032:Diet; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011110:Polymorphism, Genetic; D012307:Risk Factors; D018426:SEER Program
D002244:Carbon; D005492:Folic Acid