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According to a recent article published in the Journal of Clinical Oncology, genetic variances within 2 genes affect a patient’s response and survival to commonly used chemotherapy agents in the treatment of non-small cell lung cancer. Patients with these genetic variances may benefit from other treatment approaches for their disease.

Lung cancer remains the leading cause of death in the United States. There are several different types of cells within the lung and the type of cell from which the cancer originates affects treatment options and long-term prognosis. Non-small cell lung cancer (NSCLC) is a subset of lung cancer and refers to specific types of cells within the lung that the cancer originated. NSCLC is the most common type of lung cancer, comprising approximately 75%-80% of all lung cancers in the United States. Once the cancer has spread from its site of origin, it is referred to as advanced lung cancer. Chemotherapy remains the mainstay of treatment for advanced NSCLC and the regimen most often contains a platinum compound (cisplatin or carboplatin).

It is becoming recognized that different genetic variances between individuals diagnosed with the same type of cancer affect responses to specific treatment and also affect long-term outcomes. Much research is presently focused on understanding exactly which genetic variances affect responses to specific treatments so that treatment options may be individualized to provide optimal outcomes for each patient. Two genes, referred to as XRCC1 (Arg399Gln) and XPD (Asp312Asn) play a role in the repair of DNA damage and thus, are believed to play a large role in the development of cancer as well as a patient’s response to chemotherapy agents, such as platinum agents.

Researchers from the Harvard Cancer Center recently reviewed medical records of 103 patients diagnosed with stages III or IV NSCLC to determine if an association existed among variances in the two genes, XRCC1 and XPD, and outcomes of these patients. This study included 103 patients who had all received treatment that included a platinum compound at Massachusetts General Hospital between 1992 and 2003. Several different variables were included in the review, including different stages of cancer, different chemotherapy regimens used, ability to perform daily activities, age of the patient, etc. In the subgroup analysis of patients who had genetic variances in the XPD gene, the overall average duration of survival was only 6.6 months in patients with a variance, compared with approximately 16 months in patients with the normal gene. In the subgroup of patients with variance in the XRCC1 gene, the overall average duration of survival was only 7.7 months, compared with 17 months in patients with a normal gene. Patients who had normal copies of both of the genes had an overall average survival time of over 20 months, compared with 6.8 months in those with variances in both genes. The overall survival differences were greater in patients with stage III than those with stage IV NSCLC.

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The researchers concluded that variances with the DNA-repair genes XPD and XRCC1 appear to greatly affect survival in patients with advanced NSCLC treated with a platinum compound. These results follow logically with the role of XPD and XRCC1 and the mechanism through which platinum compounds affect cancer cells. Further research is needed to confirm this finding. Patients who have been diagnosed with NSCLC and are to undergo chemotherapy with a platinum compound may wish to speak with their physician regarding their individual risks and benefits of participation in a clinical trial further evaluating these genes or other “markers” that may affect treatment outcomes. Two sources of information regarding ongoing clinical trials inlcude the National Cancer Institute ( and Personalized clinical trial searches are also performed on behalf of

Reference: Gurubhagavatula S, Liu G, Park S, et al. XPD and XRCC1 genetic polymorphisms are prognostic factors in advanced non-small-cell ulng cancer patients treated with platinum chemotherapy. Journal of Clinical Oncology. 2004;22: 2594-2601.

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