TY - JOUR
T1 - One-carbon metabolism gene polymorphisms and risk of non-Hodgkin lymphoma in Australia
AU - Lee, Kyoung Mu
AU - Lan, Qing
AU - Kricker, Anne
AU - Purdue, Mark P.
AU - Grulich, Andrew E.
AU - Vajdic, Claire M.
AU - Turner, Jennifer
AU - Whitby, Denise
AU - Kang, Daehee
AU - Chanock, Stephen
AU - Rothman, Nathaniel
AU - Armstrong, Bruce K.
PY - 2007/12
Y1 - 2007/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=36348966549&partnerID=8YFLogxK
U2 - 10.1007/s00439-007-0431-2
DO - 10.1007/s00439-007-0431-2
M3 - Article
C2 - 17891500
AN - SCOPUS:36348966549
VL - 122
SP - 525
EP - 533
JO - Human Genetics
JF - Human Genetics
SN - 0340-6717
IS - 5
ER -