Polymorphisms in XRCC1, XRCC3, and CCND1 and Survival After Treatment for Metastatic Breast Cancer

• Published in: Journal of clinical oncology Vol. 24; no. 36; pp. 5645 - 5651
• Main Authors: BEWICK, Mary A, CONLON, Michael S. C, LAFRENIE, Robert M
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 20.12.2006; Lippincott Williams & Wilkins
• Subjects: Adult; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Cyclin D; Cyclins - genetics; Disease Progression; DNA Damage; DNA Repair; DNA-Binding Proteins - genetics; Female; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; Middle Aged; Neoplasm Metastasis; Polymorphism, Single Nucleotide; Retrospective Studies; Survival Analysis; Tumors; X-ray Repair Cross Complementing Protein 1; Genetic variability; Genotype; Breast cancer; Malignant tumor; Metastasis; Survival; Repair gene; Mammary gland diseases; BCL1 gene; Cancerology; Treatment; Advanced stage; Polymorphism
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2006.05.9923

Single nucleotide polymorphisms (SNPs) in DNA repair and cell cycle control genes may alter protein function and therefore the efficacy of DNA damaging chemotherapy. We retrospectively evaluated the association of SNPs in DNA repair genes, XRCC1-01 (Arg399Gln) and XRCC3-01 (Thr241Met), and a cell cycle control gene, CCND1-02 (A870G), with progression-free survival (PFS) and breast cancer specific survival (BCSS) in patients with metastatic breast cancer (MBC). SNPs in 95 patients with MBC enrolled onto one of five prospective clinical trials of high-dose chemotherapy and autologous stem-cell transplantation were evaluated using genotyping assays. For XRCC1-01, the hazard ratio (HR) for BCSS was 2.8 (95% CI, 1.60 to 5.00) and the HR for PFS was 2.0 (95%CI, 1.12 to 3.43). For XRCC3-01, the HR for BCSS was 2.0 (95%CI, 1.12 to 3.70) and the HR for PFS was 2.0 (95%CI, 1.09 to 3.59). For CCND1-02, the HR for BCSS was 1.8 (95%CI, 1.12 to 2.78) and the HR for PFS was 1.8 (95%CI, 1.15 to 2.85). Patients carrying one variant genotype (HR, 1.7; 95%CI, 1.07 to 2.82) or combinations of any two variant genotypes (HR, 4.7; 95% CI, 2.41 to 8.94) had significantly poorer BCSS compared with patients carrying zero variants. In multivariable analysis, XRCC1-01, presence of liver metastases, and bone metastases independently predicted BCSS. Combinations of any two variant genotypes were stronger independent predictors of BCSS and PFS than the presence of liver or bone metastases. XRCC1-01, XRCC3-01, and CCND1-01 may be predictive of survival outcome in patients with MBC treated with DNA damaging chemotherapy.