Genomic profiling associated with recurrence in patients with rectal cancer treated with chemoradiation.
OBJECTIVE
Stage II and III adenocarcinoma of the rectum has an overall 5-year survival rate of approximately 50%, and tumor recurrence remains a major problem despite an improvement in local control through chemotherapy and radiation. The efficacy of chemoradiation therapy may be significantly compromised as a result of interindividual variations in clinical response and host toxicity. Therefore, it is imperative to identify those patients who will benefit from chemoradiation therapy and those who will develop recurrent disease. In this study, we tested whether a specific pattern of 21 polymorphisms in 18 genes involved in the critical pathways of cancer progression (i.e., drug metabolism, tumor microenvironment, cell cycle regulation, and DNA repair) will predict the risk of tumor recurrence in rectal cancer patients treated with chemoradiation.


METHODS
A total of 90 patients with Stage II or III rectal cancer treated with chemoradiation were genotyped using polymerase chain reaction (PCR)-based techniques for 21 polymorphisms.


RESULTS
A polymorphism in interleukin (IL)-8 was individually associated with risk of recurrence. Classification and regression tree analysis of all polymorphisms and clinical variables developed a risk tree including the following variables: node status, IL-8, intracellular adhesion molecule-1, transforming growth factor-beta, and fibroblast growth factor receptor 4.


CONCLUSIONS
Genomic profiling may help to identify patients who are at high risk for developing tumor recurrence, and those who are more likely to benefit from chemoradiation therapy. A larger prospective study is needed to validate these preliminary data using germline polymorphisms on tumor recurrences in rectal cancer patients treated with chemoradiation.
Gordon
Michael A
MA
University of Southern California/Norris Comprehensive Cancer Center, Division of Medical Oncology, Keck School of Medicine, 1441 Eastlake Avenue, Suite 3456, Los Angeles, CA 90033, USA.
Gil
Ji
J
Lu
Bo
B
Zhang
Wu
W
Yang
Dongyun
D
Yun
Jim
J
Schneider
Sylke
S
Groshen
Susan
S
Iqbal
Syma
S
Press
Oliver A
OA
Rhodes
Katrin
K
Lenz
Heinz-Josef
HJ
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002453:Cell Cycle / Q000235:genetics; D003131:Combined Modality Therapy; D051546:Cyclooxygenase 2 / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D018450:Disease Progression; D004720:Endonucleases / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D016158:Genes, p53 / Q000235:genetics; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D011237:Predictive Value of Tests; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D012008:Recurrence; D016212:Transforming Growth Factor beta / Q000235:genetics
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D016209:Interleukin-8; D016212:Transforming Growth Factor beta; C110901:X-ray repair cross complementing protein 3; D051546:Cyclooxygenase 2; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; C071447:ERCC1 protein, human; D004720:Endonucleases