MnSOD rs4880 and XPD rs13181 polymorphisms predict the survival of breast cancer patients treated with adjuvant tamoxifen.
The enzyme manganese superoxide dismutase (MnSOD) defends against oxidative stress caused by reactive oxygen species (ROS), whereas Xeroderma pigmentosum group D (XPD) protein is involved in DNA repair. Polymorphisms in these genes have previously been associated with the outcome of breast cancer.


METHODS
Two gene polymorphisms, the MnSOD Val16Ala (rs4880A>G) and the XPD Lys751Gln (rs13181A>C), were analyzed in a cohort of 396 Finnish breast cancer patients by using PCR-RFLP-based methods in a prospective case-control study. The overall survival (OS), breast cancer-specific survival (BCSS), and relapse-free survival (RFS), assessed by using Kaplan-Meier survival analysis and multivariate Cox regression analysis, were evaluated according to the adjuvant treatments and the rs4880 and rs13181 genotypes.


RESULTS
In the combined analysis of rs4880 and rs13181 genotypes for patients treated with adjuvant tamoxifen (TAM) an increasing number of low-risk genotypes (rs4880 AA, rs4880 AG, or rs13181 AA) was significantly associated with better RFS, BCSS, and OS (n=64). In addition, there was improved BCSS and RFS among TAM-treated patients carrying the wild-type rs4880 A allele as compared with the other genotypes (n=64). The wild-type rs13181 AA genotype was similarly associated with better RFS and BCSS in the TAM-treated population (n=65).


CONCLUSIONS
This is the first study to show that the MnSOD rs4880 and XPD rs13181 polymorphisms may influence the outcome of breast cancer patients receiving adjuvant TAM monotherapy. Patients carrying the rs4880 A allele or rs13181 AA genotype may have a reduced ability to scavenge ROS and repair the DNA damage generated by TAM treatment.
Cancer Center, Kuopio University Hospital , Kuopio , Finland.
Maria
M
Tengström
Arto
A
Mannermaa
Veli-Matti
VM
Kosma
Ylermi
Y
Soini
Ari
A
Hirvonen
Vesa
V
Kataja
D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D016022:Case-Control Studies; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D013482:Superoxide Dismutase / Q000235:genetics*; D013629:Tamoxifen / Q000627:therapeutic use*; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D013482:Superoxide Dismutase; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human