Epidermal growth factor receptor intron-1 polymorphism predicts gefitinib outcome in advanced non-small cell lung cancer.
BACKGROUND
Epidermal growth factor receptor (EGFR) gene intron 1 contains a polymorphic single sequence dinucleotide repeat (CA)n whose length has been found to inversely correlate with transcriptional activity. This study was designed to assess the role of (CA)n polymorphism in predicting the outcome of gefitinib treatment in advanced non-small cell lung cancer (NSCLC).


METHODS
Blood and tumor tissue from 58 patients with advanced NSCLC submitted to gefitinib were collected. EGFR intron 1 gene polymorphism, along with EGFR gene mutation, gene copy number and immunohistochemistry expression were determined. Moreover, a panel of lung cancer cell lines characterized for EGFR intron 1 polymorphism was also studied.


RESULTS
EGFR intron 1 polymorphism showed a statistically significant correlation with the gefitinib response (response rate 25 versus 0%, for patients with a (CA)16 and with a (CA)else genotype, respectively; p = 0.044). Patients with a (CA)16 genotype had a longer survival compared with those with a (CA)else genotype (11.4 versus 4.8 months, respectively; p = 0.037). In addition, cell lines lacking the (CA)16 allele showed a statistically significant higher IC50 compared with cell lines bearing at least one (CA)16 allele (p = 0.003).


CONCLUSIONS
This study supports a potential role of EGFR intron 1 polymorphism in predicting the outcome of gefitinib treatment in advanced NSCLC.
Tiseo
Marcello
M
Division of Medical Oncology, University Hospital of Parma, Italy. mtiseo@ao.pr.it
Capelletti
Marzia
M
De Palma
Giuseppe
G
Franciosi
Vittorio
V
Cavazzoni
Andrea
A
Mozzoni
Paola
P
Alfieri
Roberta R
RR
Goldoni
Matteo
M
Galetti
Maricla
M
Bortesi
Beatrice
B
Bozzetti
Cecilia
C
Loprevite
Maura
M
Boni
Luca
L
Camisa
Roberta
R
Rindi
Guido
G
Petronini
Pier Giorgio
PG
Ardizzoni
Andrea
A
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000235:genetics; D018900:Dinucleotide Repeats / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D018628:Gene Dosage; D006801:Humans; D007124:Immunoenzyme Techniques; D007438:Introns / Q000235:genetics*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib