Association of a XRCC3 polymorphism and rectum mean dose with the risk of acute radio-induced gastrointestinal toxicity in prostate cancer patients.
OBJECTIVE
We have performed a case-control study among prostate cancer patients treated with three-dimensional conformational radiotherapy (3D-CRT) in order to investigate the association between single nucleotide polymorphisms (SNPs), treatment and patient features with gastrointestinal and genitourinary acute toxicity.


METHODS
A total of 698 patients were screened for 14 SNPs located in the ATM, ERCC2, LIG4, MLH1 and XRCC3 genes. Gastrointestinal and genitourinary toxicities were recorded prospectively using the Common Terminology Criteria for Adverse Events v3.0.


RESULTS
The XRCC3 SNP rs1799794 (G/G OR=5.65; 95% CI: 1.95-16.38; G/A OR=2.75; 95% CI: 1.25-6.05; uncorrected p-value=2.8×10(-03); corrected p-value=0.03; FDR q-value=0.06) as well as the mean dose received by the rectum (OR=1.06; 95% CI: 1.02-1.1; uncorrected p-value=2.49×10(-03); corrected p-value=0.03; FDR q-value=0.06) were significantly associated with gastrointestinal toxicity after correction for multiple testing. Those patients who undergone previous prostatectomy were less prone to develop genitourinary toxicity (OR=0.38; 95% CI: 0.18-0.71; uncorrected p-value=4.95×10(-03); corrected p-value=0.03; FDR q-value=0.08). Our study excludes the possibility of a >2-fold risk increase in genitourinary acute toxicity being due to rs1801516 ATM SNP, the rs1805386 and rs1805388 LIG4 markers, as well as all the SNPs evaluated in the ERCC2, MLH1 and XRCC3 genes.


CONCLUSIONS
The XRCC3 rs1799794 SNP and the mean dose received by the rectum are associated with the development of gastrointestinal toxicity after 3D-CRT.
Fundación Pública Galega de Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica-USC, CIBERER, IDIS, Santiago de Compostela, Spain.
Laura
L
Fachal
Antonio
A
Gómez-Caamaño
Paula
P
Peleteiro
Ana
A
Carballo
Patricia
P
Calvo-Crespo
Manuel
M
Sánchez-García
Ramón
R
Lobato-Busto
Angel
A
Carracedo
Ana
A
Vega
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005500:Follow-Up Studies; D005767:Gastrointestinal Diseases / Q000209:etiology* / Q000235:genetics; D041981:Gastrointestinal Tract / Q000528:radiation effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood / Q000209:etiology / Q000235:genetics* / Q000532:radiotherapy* / Q000601:surgery; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects*; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects; D012007:Rectum / Q000528:radiation effects*; D012307:Risk Factors; D013997:Time Factors; D001743:Urinary Bladder / Q000528:radiation effects; D014566:Urogenital System / Q000528:radiation effects
D015415:Biomarkers; D004268:DNA-Binding Proteins; C110901:X-ray repair cross complementing protein 3