Lymphotoxin alfa and receptor-interacting protein kinase 1 gene polymorphisms may correlate with prognosis in patients with diffuse large B cell lymphoma treated with R-CHOP.
OBJECTIVE
Diffuse large B cell lymphoma (DLBCL) is a heterogenous disease entity due to diverse clinical outcomes to treatment. Most anticancer agents, regardless of their distinct mechanisms of action, ultimately kill cancer cells by inducing apoptosis. Accordingly, the present study analyzed the impact of polymorphisms of apoptosis-related genes on outcome in DLBCL patient treated with R-CHOP.


METHODS
Ninety patients with DLBCL treated with R-CHOP were enrolled in the present study. The genomic DNA was extracted from paraffin-embedded tissue and 22 polymorphisms of 18 apoptosis-related genes were assessed using a polymerase chain reaction-restriction fragment length polymorphism assay.


RESULTS
All the evaluable patients were responsive to R-CHOP. The multivariate analysis showed that the AA genotype of lymphotoxin alpha (LTA) C804A (rs1041981) and GG genotype of RIPK1 G83A (rs2272990) were significantly correlated with a worse time to progression (TTP) compared with the combined C/A and C/C genotype and the combined G/A and A/A genotype (hazard ratio [HR]=7.92; 95% confidence interval [CI]=1.42-44.18; P=0.018 and HR=20.02; 95% CI=1.59-251.52; P value=0.018, respectively), whereas no association was observed between the other polymorphisms and TTP.


CONCLUSIONS
The polymorphisms of LTA (rs1041981) and RIPK1 (rs2272990) may correlate with TTP in patients with DLBCL treated with R-CHOP.
Chae
Yee Soo
YS
Department of Oncology/Hematology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, 700-721, Korea.
Kim
Jong Gwang
JG
Sohn
Sang Kyun
SK
Moon
Joon Ho
JH
Kim
Shi Nae
SN
Lee
Su Jeong
SJ
Park
Tae-In
TI
Lee
Myung-Hoon
MH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018450:Disease Progression; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005787:Gene Frequency; D006801:Humans; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000235:genetics; D000069283:Rituximab; D013997:Time Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D008233:Lymphotoxin-alpha; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; C506249:RIPK1 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D011241:Prednisone