One-carbon metabolism gene polymorphisms and risk of non-Hodgkin lymphoma in Australia.
Dysregulation of the one-carbon metabolic pathway, which controls nucleotide synthesis and DNA methylation, may promote lymphomagenesis. We evaluated the association between polymorphisms in one-carbon metabolism genes and risk of non-Hodgkin lymphoma (NHL) in a population-based case-control study in Australia. Cases (n = 561) and controls (n = 506) were genotyped for 14 selected single-nucleotide polymorphisms in 10 genes (CBS, FPGS, FTHFD, MTHFR, MTHFS, MTR, SHMT1, SLC19A1, TCN1, and TYMS). We also conducted a meta-analysis of all studies of Caucasian populations investigating the association between MTHFR Ex5+79C > T (a.k.a., 677C>T) and NHL risk. A global test of 13 genotypes was statistically significant for diffuse large B-cell lymphoma (DLBCL; P = 0.008), but not for follicular lymphoma (FL; P = 0.27) or all NHL (P = 0.17). The T allele at MTHFR Ex5+79 was marginally significantly associated with all NHL (OR = 1.25, 95% CI = 0.98-1.59) and DLBCL (1.36, 0.96-1.93). The T allele at TYMS Ex8+157 was associated with a reduced risk of FL (0.64, 0.46-0.91). An elevated risk of NHL was also observed among carriers of the G allele at FTHFD Ex21+31 (all NHL, 1.31, 1.02-1.69; DLBCL, 1.50, 1.05-2.14). A meta-analysis of 11 studies conducted in Caucasian populations of European origin (4,121 cases and 5,358 controls) supported an association between the MTHFR Ex5+79 T allele and increased NHL risk (additive model, P = 0.01). In conclusion, the results of this study suggest that genetic polymorphisms of one-carbon metabolism genes such as MTHFR and TYMS may influence susceptibility to NHL.
Lee
Kyoung-Mu
KM
Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, 6120 Executive Blvd. EPS 8118, Bethesda, MD 20892-7240, USA. leekyou@mail.nih.gov
Lan
Qing
Q
Kricker
Anne
A
Purdue
Mark P
MP
Grulich
Andrew E
AE
Vajdic
Claire M
CM
Turner
Jennifer
J
Whitby
Denise
D
Kang
Daehee
D
Chanock
Stephen
S
Rothman
Nathaniel
N
Armstrong
Bruce K
BK
D000328:Adult; D000368:Aged; D000483:Alleles; D001315:Australia; D002244:Carbon / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D016393:Lymphoma, B-Cell / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*; D016399:Lymphoma, T-Cell / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D002244:Carbon