Genetic polymorphisms in the metabolic pathway and non-Hodgkin lymphoma survival.
Metabolic pathway enzymes, such as Cytochrome P450 (CYP), glutathione S-transferase (GST), and N-acetyltransferases (NAT) are involved in activation and detoxification of environmental carcinogens as well as drug metabolism. We hypothesized that the genetic variations in such metabolic pathways may affect NHL prognosis and survival. Follow-up information of 496 female NHL incident cases diagnosed during 1996-2000 in Connecticut were abstracted from the Connecticut Tumor Registry in 2008; survival analyses were conducted by comparing the Kaplan-Meier curves, and hazard ratios (HR) were computed from the Cox Proportional Hazard models adjusting for demographic and tumor characteristics which were suggested by previous studies to be determinants of NHL survival. We identified six SNPs from four metabolism genes (CYP2E1, GSTP1, GSTT1, and NAT1) that were associated with NHL survival. Specifically, polymorphisms in GSTT1 were associated with follicular lymphoma survival; and polymorphisms in CYP2E1, GSTP1, and NAT1 were associated with survival of chronic lymphocytic leukemia/small lymphocytic lymphoma. Our study suggests that genetic polymorphisms in metabolic pathways may help improve the prediction of NHL survival and prognosis.
Han
Xuesong
X
Yale University School of Public Health, 60 College Street, New Haven, CT 06520-8034, USA.
Zheng
Tongzhang
T
Foss
Francine M
FM
Lan
Qing
Q
Holford
Theodore R
TR
Rothman
Nathaniel
N
Ma
Shuangge
S
Zhang
Yawei
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001191:Arylamine N-Acetyltransferase / Q000235:genetics; D003237:Connecticut; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008224:Lymphoma, Follicular / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012042:Registries; D055815:Young Adult
D007527:Isoenzymes; D019392:Cytochrome P-450 CYP2E1; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase