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Int. J. Mol. Sci. 2012, 13(12), 16500-16513;

Identification of Candidate Polymorphisms on Stress Oxidative and DNA Damage Repair Genes Related with Clinical Outcome in Breast Cancer Patients

Institute of Health Research INCLIVA, Av. Blasco Ibañez, 17, Valencia 46010, Spain
Department of Haematology and Medical Oncology. Valencia University Clinical Hospital, Valencia 46010, Spain
Genotyping and Genetic Diagnosis Unit, Valencia University Clinical Hospital, Institute of Health Research INCLIVA, Valencia 46010, Spain
Author to whom correspondence should be addressed.
Received: 10 October 2012 / Revised: 23 November 2012 / Accepted: 27 November 2012 / Published: 5 December 2012
(This article belongs to the Special Issue DNA Damage and Repair in Degenerative Diseases)
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Diverse polymorphisms have been associated with the predisposition to develop cancer. On fewer occasions, they have been related to the evolution of the disease and to different responses to treatment. Previous studies of our group have associated polymorphisms on genes related to oxidative stress (rs3736729 on GCLC and rs207454 on XDH) and DNA damage repair (rs1052133 on OGG1) with a predisposition to develop breast cancer. In the present work, we have evaluated the hypothesis that these polymorphisms also play a role in a patient’s survival. A population-based cohort study of 470 women diagnosed with primary breast cancer and a median follow up of 52.44 months was conducted to examine the disease-free and overall survival in rs3736729, rs207454 and rs1052133 genetic variants. Adjusted Cox regression analysis was used to that end. The Kaplan-Meier analysis shows that rs3736729 on GCLC presents a significant association with disease-free survival and overall survival. The polymorphisms rs1052133 on OGG1 and rs207454 on XDH show a trend of association with overall survival. The analysis based on hormonal receptor status revealed a stronger association. The CC genotype on rs207454 (XDH) was significantly associated with lower time of disease free survival (p = 0.024) in progesterone receptor negative (PGR−) patients and rs3736729 (GCLC) was significantly associated with disease free survival (p = 0.001) and overall survival (p = 0.012) in the subgroup of estrogen receptor negative (ER−) patients. This work suggests that unfavorable genetic variants in the rs207454 (XDH) and rs3736729 (GCLC) polymorphisms may act as predictors of the outcome in negative progesterone receptor and negative estrogen receptor breast cancer patients, respectively. View Full-Text
Keywords: genetic variants; GCLC; XDH; OGG1; breast cancer; survival genetic variants; GCLC; XDH; OGG1; breast cancer; survival
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Rodrigues, P.; Furriol, J.; Bermejo, B.; Chaves, F.J.; Lluch, A.; Eroles, P. Identification of Candidate Polymorphisms on Stress Oxidative and DNA Damage Repair Genes Related with Clinical Outcome in Breast Cancer Patients. Int. J. Mol. Sci. 2012, 13, 16500-16513.

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