TNF superfamily gene polymorphism as prognostic factor in early breast cancer.
OBJECTIVE
Since apoptosis may play a role in the prognosis of breast cancer, the present study analyzed the polymorphisms of apoptosis-related genes and their impact on the survival of 240 patients with early invasive ductal breast cancer.


METHODS
The genomic DNA was extracted from paraffin-embedded tumor-free tissue or blood, and 12 single nucleotide polymorphisms (SNPs) of 11 apoptosis-related genes in the apoptosis pathway determined using a Sequenom MassARRAY system.


RESULTS
During the median follow-up of 53.4 (range 2.9-205.9) months, 37 relapses and 22 deaths occurred. Among the target polymorphisms, the tumor necrosis factor superfamily member 10 gene polymorphism (TNFSF10 rs1131532) in a recessive model of the T allele and prostaglandin-endoperoxide synthase 2 gene polymorphism (PTGS2 rs5275) in a dominant model of the C allele were associated with survival in a log-rank test. The TT genotype of TNFSF10 (rs1131532) was also significantly correlated with a lower disease-free, distant disease-free, and overall survival in a multivariate analysis (HR = 3.304, 4.757, and 6.459; P = 0.002, 0.001, and 0.009, respectively), while PTGS2 rs5275 was only associated with a higher distant disease-free survival (HR = 0.302; P = 0.041). No clinicopathologic difference was observed according to the genotypes of these two polymorphisms.


CONCLUSIONS
The TNFSF10 (rs1131532) polymorphism was identified as a possible prognostic factor of survival in patients with operated invasive breast cancer.
Jung
Jin Hyang
JH
Department of Surgery, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Jung-Gu, Daegu, Korea.
Chae
Yee Soo
YS
Moon
Joon Ho
JH
Kang
Byung Woog
BW
Kim
Jong Gwang
JG
Sohn
Sang Kyun
SK
Park
Ji Young
JY
Lee
Myung Hoon
MH
Park
Ho Yong
HY
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D044584:Carcinoma, Ductal / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000235:genetics; D005260:Female; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014408:Biomarkers, Tumor; C439524:TNF protein, human; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2