Back to Search
Start Over
Common European Mitochondrial Haplogroups in the Risk for Radiation-induced Subcutaneous Fibrosis in Breast Cancer Patients
- Source :
- Clinical Oncology. 28:365-372
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Aims The contribution of mitochondrial DNA (mtDNA) variations to clinical radiosensitivity is largely unknown. In the present study, we evaluated the association between mtDNA haplogroups and the risk of radiation-induced subcutaneous fibrosis after postoperative radiotherapy in breast cancer patients. Materials and methods Subcutaneous fibrosis was scored according to the Late Effects of Normal Tissue-Subjective Objective Management Analytical (LENT-SOMA) scale in 286 Italian breast cancer patients who received radiotherapy after breast-conserving surgery. Eight mtDNA single nucleotide polymorphisms that define the nine major haplogroups in the European population were determined by polymerase chain reaction restriction fragment length polymorphism analysis on genomic DNA extracted from peripheral blood. Results In a Kaplan–Meier analysis evaluated by the Log-rank test, carriers of haplogroup H were found to be at lower risk of grade ≥2 subcutaneous fibrosis ( P = 0.018) compared with all other haplotypes combined. In the multivariate Cox regression analysis adjusted for clinical factors (body mass index, breast diameter, adjuvant treatment, dose per fraction, radiation type and acute skin toxicity), haplogroup H emerged as a protective factor for moderate to severe radiation-induced fibrosis at a nominal significance level (hazard ratio: 0.50, 95% confidence interval 0.27–0.92, P = 0.027), which did not survive correction for multiple testing. Conclusions Our results suggest a protective effect of the mitochondrial haplogroup H in the development of radiation-induced fibrosis in breast cancer patients. However, the loss of statistical significance after correction for multiple comparisons and the lack of an independent validation cohort make our findings preliminary, requiring further confirmation in large-scale prospective studies.
- Subjects :
- 0301 basic medicine
Oncology
medicine.medical_specialty
Pathology
Haplogroup H
subcutaneous fibrosis
Breast Neoplasms
Kaplan-Meier Estimate
mitochondrial DNA
DNA, Mitochondrial
Polymorphism, Single Nucleotide
White People
Haplogroup
03 medical and health sciences
Breast cancer
0302 clinical medicine
Risk Factors
Fibrosis
normal tissue radiosensitivity
radiotherapy
Internal medicine
medicine
Humans
Radiology, Nuclear Medicine and imaging
Breast
Radiation Injuries
Prospective cohort study
Subcutaneous fibrosis
business.industry
Haplotype
Middle Aged
medicine.disease
030104 developmental biology
Haplotypes
030220 oncology & carcinogenesis
Female
business
Polymorphism, Restriction Fragment Length
Human mitochondrial DNA haplogroup
Subjects
Details
- ISSN :
- 09366555
- Volume :
- 28
- Database :
- OpenAIRE
- Journal :
- Clinical Oncology
- Accession number :
- edsair.doi.dedup.....d193b4ff869390c265161ab9aa15f7ac