Association between XRCC1 G399A Polymorphism and Late Complications to Radiotherapy in Saudi Head and Neck Cancer Patients.
BACKGROUND
It has been hypothesized that patient to patient variation in normal tissue reactions to radiotherapy is associated with the presence of polymorphic variations in genes involved in DNA repair.


OBJECTIVE
To test for a possible association between two single-nucleotide polymorphisms (SNPs), XRCC1 399 G>A Arg/Gln and XRCC3 241 C>T Thr/Met and late reactions to radiotherapy.


METHODS
In this case control study, 50 Head and Neck cancer patients were retrospectively recruited. The grade (G) of fibrosis, a late complication to radiotherapy, was scored using the RTOG/EORTC grading system. Radiosensitive patients with moderate to severe subcutaneous and deep tissue fibrosis (cases, G2-3, n=25) where matched with patients with minimal fibrotic reactions (control, G0-1, n=25). The two nonsynonymous SNPs were genotyped by direct sequencing of DNA extracted from blood or cultured fibroblasts.


RESULTS
Allelic frequency showed significant association with grade of fibrosis for XRCC1 399 G/A (p=0.05), but not for XRCC3 241 C>T (p=0.10).


CONCLUSIONS
This pilot study corroborates the association between XRCC1 399 G>A and risk of late normal tissue complications following radiotherapy in our patients. Large studies are required to unravel more SNPs that can influence radiosensitivity and ascertain the associations with reactions to radiotherapy in order to be used as genetic predictive biomarkers of individual radiosensitivity.


BACKGROUND
Single nucleotide polymorphism - Radiosensitivity - Late reactions to radiotherapy - XRCC1 - XRCC3.
Alsbeih
Ghazi Atiyeh
GA
The Departments of Biomedical Physics, King Saud University, Riyadh, Saudi Arabia.
El-Sebaie
Medhat Mohamed
MM
Al-Rajhi
Nasser Mohamed
NM
Al-Harbi
Najla Mohamed
NM
Al-Hadyan
Khaled Saleh
KS
Al-Buhairi
Muneera Hamad
MH
Moftah
Belal Ali
BA
Al-Shabanah
Mohammad Othman
MO
Abu-Amero
Khaled Kader
KK