Analysis of common germline polymorphisms as prognostic factors in patients with lymph node-positive breast cancer

• Published in: Journal of cancer research and clinical oncology 2010-12, Vol.136 (12), p.1813-1819
• Main Authors: Knechtel, Gudrun, Hofmann, Günter, Gerger, Armin, Renner, Wilfried, Langsenlehner, Tanja, Szkandera, Joanna, Wolf, Gerald, Samonigg, Hellmut, Krippl, Peter, Langsenlehner, Uwe
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic agents; Biological and medical sciences; Breast cancer; breast neoplasms; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer Research; Disease Progression; Disease-Free Survival; fas Receptor - genetics; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Germ-Line Mutation; Gynecology. Andrology. Obstetrics; Hematologic and hematopoietic diseases; Hematology; Humans; Interleukin-10 - genetics; Internal Medicine; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymph node-positive; Lymph Nodes - pathology; Lymphatic Metastasis; Lymphatic system; Mammary gland diseases; Medical prognosis; Medical sciences; Medicine; Medicine & Public Health; Metastasis; Middle Aged; Multivariate Analysis; Neoplasm Staging; Oncology; Original Paper; Pharmacology. Drug treatments; Polymorphism; Polymorphism, Single Nucleotide; Prognosis; Tumors
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-010-0839-2

Purpose Women with breast cancer that initially involves local lymph nodes have a higher risk for local recurrence or developing metastases. Recent data suggest that germline polymorphism is a significant, previously unrecognized factor in breast cancer progression and metastasis. We assessed the influence of 16 selected common germline polymorphisms in disease-free survival and overall survival among 216 women diagnosed with lymph node-positive breast cancer. Results The rare allele of FAS 1377G>A was significantly associated with prolonged disease-free survival (P = 0.012, risk ratio of recurrence (RR) = 0.557, 95% confidence interval (CI) = 0.353-0.878) in univariate analysis. After adjusting for known breast cancer prognostic factors the association remained significant (P = 0.050, RR = 0.500, CI = 0.309-0.809). In overall survival analysis we found a significant association of the FAS 1377G>A (P = 0.040, RR = 0.451, CI = 0.496-1.188) and IL10 592C>A polymorphisms (P = 0.020, RR = 1.707, CI = 1.087-2.680) in the univariate Cox regression. The effect remained statistically significant in the multivariate analysis for the IL10 592C>A polymorphism (P = 0.013, RR 1.841, CI 1.140-2.973). No association was found for MTHFR 677C>T, VEGF 936C>T, CCND1 870G>A, TGFB1 29T>C, FASLG 844C>T, FAS 670A>G, GPB3 825C>T, ITGA2 807C>T, ITGA2 1648G>A, ITGB3 176T>C, MMP1 -1607 1G/2G, MMP3 5A/6A, PTGS2 8473T>C, IL10 592C>A and SULT1A1 638G>A polymorphisms and disease-free survival or overall survival. Conclusions Our data suggest that the FAS 1377G>A and IL10 592C>A polymorphisms could modify disease-free and overall survival in women with lymph node-positive breast cancer.