|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Journal of Clinical Oncology, Vol 26, No 19 (July 1), 2008: pp. 3289-a-3290 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2008.17.3880
Vascular Endothelial Growth Factor Polymorphisms in Early-Stage Non–Small-Cell Lung CancerDepartment of Medicine, Roswell Park Cancer Institute, Buffalo, NY
Department of Biostatistics, Roswell Park Cancer Institute, Buffalo, NY To the Editor: In their publication, Heist et al1 describe an association between vascular endothelial growth factor (VEGF) polymorphisms and survival in patients with surgically resected stage I and II non–small-cell lung cancer (NSCLC). Patient data was derived from the databank of a molecular epidemiology study at Massachusetts General Hospital (MGH; Boston, MA) wherein patients with histologically confirmed NSCLC have been recruited prospectively since 1992. The authors concluded that the variant C allele of the VEGF +405G>C polymorphism was associated with significantly improved survival among patients with early-stage NSCLC treated with surgical resection. In addition, a trend toward improved survival was seen among patients carrying the variant T allele of the VEGF +936C >T polymorphism and a significant improved survival was reported in patients carrying an increasing numbers of variant alleles in the +936C>T and +405G>C polymorphisms. We commend the authors’ efforts as this is the first peer-reviewed publication analyzing the significance of VEGF genetic polymorphisms in NSCLC, primarily as the genetic changes studies involve key regulatory sites in the VEGF gene. We would be interested in knowing a few more details, which will help interpret the data better. Was there any data collected with respect to the cause of death? There is no mention about the disease-free survival. It would be important to know whether the cause of death was disease progression, postoperative complications, or other causes related or unrelated to VEGF levels (ie, coronary artery disease). This would help in comparing the association of VEGF polymorphisms and outcomes from NSCLC better. Furthermore, it would be interesting to know what the plasma VEGF levels were and if VEGF levels were affected by the different genetic polymorphisms studied. Any association between polymorphisms and plasma VEGF levels were not reported in the study. Several studies have attempted to correlate the survival outcomes in patients with various malignancies (eg, colon, gastric, ovarian) and VEGF polymorphisms with variable outcomes questioning the role of VEGF polymorphisms.2-8 Yet, there exists a considerable disagreement on the exact function of the +405G>C polymorphism. Hence, it would be helpful to look at the VEGF polymorphisms and their relationship with the plasma VEGF levels in lung cancer. In case a relationship is found between VEGF polymorphisms, plasma VEGF levels, and survival, this may potentially provide an easier prognostic tool for routine clinical practice in contrast to genetic testing for VEGF polymorphisms. While overall survival has been the most important end point in any clinical cancer trial, we question its true value in this observational study. Patients with surgically resected stage I or II NSCLC have 5-year survival rates of 50% and 32%, respectively.9 It is uncertain if the difference in survival between subgroups with different genetic polymorphisms observed is a direct reflection of the biology of NSCLC. In this particular setting, relapse rates, disease-free-survival, duration of remission, or cancer-related death would be important end points. Was any disease recurrence data analyzed? Although a retrospective review of data has limitations, it would be interesting to look at the relationship of VEGF polymorphisms with disease-free survival/time to relapse. Statistically, the hazard ratios (HRs) for survival on the basis of number of variant alleles show that the individual HRs were not found to significantly differ from one as conveyed by the reported confidence intervals (crude HR for three alleles, adjusted HR for one allele, and adjusted HR for three alleles). There is a significant P trend reported (.006) for the crude as well as adjusted HRs but the final analysis reveals a significant P value (.04) when overall survival among all variant allele subgroups is compared. We would be interested in knowing more about the analysis and the authors’ opinion about why the HRs differed in significance when compared between crude and adjusted (adjusted for age, sex, smoking status, and stage) values within each variant allele subgroup. The major strengths of this study are the large number of enrolled patients and the extensive epidemiologic and survival data available. The study does evaluate an important question of the biologic and clinical importance of VEGF polymorphisms and their relationship with survival outcomes in lung cancer. It will be interesting to check the VEGF levels from the stored blood samples, if available, to establish their relationship with VEGF polymorphisms. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES
1. Heist RS, Zhai R, Liu G, et al: VEGF polymorphisms and survival in early-stage non-small-cell lung cancer. J Clin Oncol 26:856-862, 2008 2. Renner W, Kotschan S, Hoffmann C, et al: A common 936 C/T mutation in the gene for vascular endothelial growth factor is associated with vascular endothelial growth factor plasma levels. J Vasc Res 37:443-448, 2000[CrossRef][Medline] 3. Watson CJ, Webb NJ, Bottomley MJ, et al: Identification of polymorphisms within the vascular endothelial growth factor (VEGF) gene: Correlation with variation in VEGF protein production. Cytokine 12:1232-1235, 2000[CrossRef][Medline] 4. Stevens A, Soden J, Brenchley PE, et al: Haplotype analysis of the polymorphic human vascular endothelial growth factor gene promoter. Cancer Res 63:812-816, 2003 5. Lu H, Shu XO, Cui Y, et al: Association of genetic polymorphisms in the VEGF gene with breast cancer survival. Cancer Res 65:5015-5019, 2005 6. Tzanakis N, Gazouli M, Rallis G, et al: Vascular endothelial growth factor polymorphisms in gastric cancer development, prognosis, and survival. J Surg Oncol 94:624-630, 2006[CrossRef][Medline] 7. Hefler LA, Mustea A, Konsgen D, et al: Vascular endothelial growth factor gene polymorphisms are associated with prognosis in ovarian cancer. Clin Cancer Res 13:898-901, 2007 8. Zhai R, Gong MN, Zhou W, et al: Genotypes and haplotypes of the VEGF gene are associated with higher mortality and lower VEGF plasma levels in patients with ARDS. Thorax 62:718-722, 2007 9. Suzuki K, Nagai K, Yoshida J, et al: Prognostic factors in clinical stage I non-small cell lung cancer. Ann Thorac Surg 67:927-932, 1999 Related Reply
Related Article
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
