Trial Information

A Study of Gene Polymorphisms and Normal Tissue Radiation Injury in Patients Treated for Breast, Prostate, Brain, Lung, and Head and Neck Cancers

Major innovations in radiotherapy (RT) delivery (3D conformal RT, intensity modulated RT)
now permit RT dose escalation to be tested as a means of improving disease control in many
tumour sites. With delivery innovations, life-threatening toxicity occurs rarely, but
significant clinical toxicity is common. In previous work the investigators have studied a
cohort of 98 prostate patients who received dose-escalated 3D-CRT and have obtained evidence
of genetic and dosimetric factors underlying rectal/bladder toxicity. They posit that the
late radiation toxicity disease state has significant genetic determinants in other
malignancies. These determinants are neither understood nor accounted for in selection of
treatment, and the investigators propose to study additional well-characterized cohorts, who
are clinically well from a disease control perspective, given that comprehensive dosimetric
and outcome information is available on all.

For a thorough understanding of the molecular processes underlying tissue responses to
radiation damage, the investigators propose a genomic analysis. Their working hypothesis is
that normal organ toxicity will be associated with patient genetics as measured by single
nucleotide polymorphisms (SNPs) in a select group of genes. The criteria for selecting SNPs
will be based on a candidate gene approach, choosing genes implicated or demonstrated in DNA
repair pathways and radiation-induced tissue damage/tissue homeostasis. Analysis of these
data will use both statistically based bioinformatics approaches.