Polymorphisms in ERCC1 and grade 3 or 4 toxicity in non-small cell lung cancer patients.
OBJECTIVE
ERCC1 is a lead enzyme in the nucleotide excision repair pathway of DNA repair. Polymorphisms have been identified in the ERCC1 gene, the C8092A and codon 118 polymorphisms, which may lead to an altered capacity to regenerate damaged normal tissue and greater treatment-related toxicity.


METHODS
Using logistic regression models, we evaluated the ERCC1 C8092A and codon 118 polymorphisms and their association with the occurrence of grade 3 or 4 toxicity in 214 stage III and IV non-small cell lung cancer patients treated first line with platinum-based chemotherapy. Adjusting covariates were performance status and type of treatment regimen.


RESULTS
There was no statistically significant association between either the C8092A or codon 118 polymorphism and overall or hematologic grade 3 or 4 toxicity. However, carrying at least one variant ERCC1 C8092A allele was associated with a significantly increased risk of grade 3 or 4 gastrointestinal toxicity (adjusted odds ratio, 2.33; 95% confidence interval, 1.07-5.05; P = 0.03).


CONCLUSIONS
Adjusting for performance status and type of treatment regimen, carrying at least one ERCC1 8092A allele is associated with a >2-fold increase in grade 3 or 4 gastrointestinal toxicity among platinum-treated non-small cell lung cancer patients.
Suk
Rebecca
R
Massachusetts General Hospital and Harvard School of Public Health, Boston, MA 02115, USA.
Gurubhagavatula
Sarada
S
Park
Sohee
S
Zhou
Wei
W
Su
Li
L
Lynch
Thomas J
TJ
Wain
John C
JC
Neuberg
Donna
D
Liu
Geoffrey
G
Christiani
David C
DC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D004358:Drug Therapy / Q000706:statistics & numerical data; D064420:Drug-Related Side Effects and Adverse Reactions; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index; D014839:Vomiting / Q000139:chemically induced
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C071447:ERCC1 protein, human; D004720:Endonucleases