Identifying Genetic Factors That Predict Response to Chemotherapy in NSCLC

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A genetic variation in the chemokine-like receptor 1 (CMKLR1) gene was statistically significantly associated with poor overall survival in patients with non–small cell lung cancer (NSCLC) who were treated with platinum-based chemotherapy with or without radiation. The variation was identified by a genome-wide scan performed to identify genetic variants associated with decreased overall survival in these patients and was validated in patient populations of more than 300 each at The University of Texas MD Anderson Cancer Center in Houston and the Mayo Clinic. The patients had stage III or IV NSCLC, had smoked, and had not had surgery.

“This study provides additional biomarkers that can be integrated with known epidemiological, clinical, and genetic risk factors to potentially identify patients who are more likely to respond to chemotherapy, thereby helping the physician develop individualized treatment regimens,” the investigators concluded in a report in the Journal of the National Cancer Institute. They noted that response to platinum-based chemotherapy, the main treatment for NSCLC, varies among patients, but the 1-year survival rate is just 29%.

The potential biomarker is a germline genetic variation known as single-nucleotide polymorphism (SNP) rs1878022. “Germline SNPs are stable markers that do not vary with disease severity and can be screened for using DNA isolated from a blood sample before treatment,” the investigators noted. In contrast, somatic alterations, which can also help select targeted therapy, require tumor specimens.

Wu X, et al: J Natl Cancer Inst 103:817-825, 2011.




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