Abstract
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.
Highlights
IntroductionIt has been established that polymorphism variants on low penetrance genes can contribute to the risk of breast cancer [3,4,5,6,7,8,9,10,11]
Breast cancer is one of the most common cancers among women worldwide
We have found an association of the polymorphism rs3736729 on the GCLC gene with breast cancer (OR = 0.85 and p-value = 0.054) in a recessive model
Summary
It has been established that polymorphism variants on low penetrance genes can contribute to the risk of breast cancer [3,4,5,6,7,8,9,10,11]. The degree of oxidative stress has been linked to the development of breast cancer [21]. Reactive oxygen species (ROS) are the natural product of respiration and other normal cellular processes. These species have been shown to induce cell death by causing different types of cellular damage associated with lipid peroxidation and alterations of nucleic acids and proteins [22], triggering apoptosis through the mitochondria [23]
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