Polymorphisms in the FAS and FASL genes and survival of early stage non-small cell lung cancer.
OBJECTIVE
This study was conducted to investigate the impact of functional polymorphisms in the FAS and FASL genes on the survival of early stage non-small cell lung cancer (NSCLC) patients.


METHODS
Three hundred and thirty-eight consecutive patients with surgically resected NSCLC were enrolled. The FAS -1377G>A (rs2234767) and -670A>G (rs1800682) and FASL -844C>T (rs763110) polymorphisms were investigated. Immunohistochemistry was used to assess FAS protein expression in tumors. The genotype and haplotype associations with survival were analyzed using Cox proportional hazards model, Kaplan-Meier method, and the log-rank test.


RESULTS
Patients with the GG and combined AG+GG genotypes of the FAS -670A>G locus had a significantly decreased survival when compared with patients with the AA genotype [adjusted hazard ratio=1.71, 95% confidence interval (95% CI)=1.06-2.77, and P=0.03; and adjusted hazard ratio=1.48, 95% CI=1.01-2.20, and P=0.047, respectively]. In addition, the FAS -1377G/-670G and -1377A/-670G haplotypes exhibited a significantly lower survival compared with the -1377G/-670A haplotype (adjusted hazard ratio=1.87, 95% CI=1.20-2.91, and P=0.006; and adjusted hazard ratio=1.31, 95% CI=1.05-1.65, P=0.02, respectively). Strongly positive FAS immunostaining was significantly less frequent in patients with the FAS -670 AG+GG genotype than in patients with the -670 AA genotype (4.5% versus 10.8%; P=0.04).


CONCLUSIONS
The FAS -670A>G polymorphism may affect survival in early-stage NSCLC. The analysis of the FAS -670A>G polymorphism can help identify patients at high risk for a poor disease outcome.
Park
Jae Yong
JY
Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. jaeyong@knu.ac.kr
Lee
Won-Kee
WK
Jung
Duk-Ku
DK
Choi
Jin-Eun
JE
Park
Tae-In
TI
Lee
Eung-Bae
EB
Cho
Sukki
S
Park
Ji-Young
JY
Cha
Sung-Ick
SI
Kim
Chang-Ho
CH
Kam
Sin
S
Jung
Tae Hoon
TH
Jheon
Sanghoon
S
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D053222:Fas Ligand Protein / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D019014:fas Receptor / Q000235:genetics* / Q000378:metabolism
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D012333:RNA, Messenger; D019014:fas Receptor