Does variability in normal tissue reactions after radiotherapy have a genetic basis - where and how to look for it?

被引:154
作者
Andreassen, CN [1 ]
Alsner, J [1 ]
Overgaard, J [1 ]
机构
[1] Aarhus Univ Hosp, Dept Expt Clin Oncol, DK-8000 Aarhus C, Denmark
关键词
radiotherapy; radiosensitivity; normal tissue morbidity; predictive assays; genetics; single nucleotide polymorphisms;
D O I
10.1016/S0167-8140(02)00154-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Cancer patients exhibit large patient-to-patient variability in normal tissue reactions after radiotherapy. Several observations support the hypothesis that clinical normal tissue radiosensitivity is influenced by genetic factors. However, very little is known about the genetic variation possibly underlying inter-individual differences in normal tissue reactions when unselected cancer patients undergo radiotherapy. It seems reasonable to assume that clinical radiosensitivity of normal tissues should be regarded as a so-called complex trait depending on the combined effect of several different genetic alterations, Single nucleotide polymorphisms (SNPs) make up 90% of naturally occurring sequence variation in the human genome and SNPs in genes related to the biological response to ionising radiation may affect clinical radiosensitivity. Rare genetic variants could also possibly play an important role. Thus, the 'allelic architecture' underlying differences in normal tissue reactions may be rather complicated. Recent advances in high throughput genotyping and bio-informatics provide unprecedented opportunities to unravel the genetic basis of clinical normal tissue radiosensitivity. However, to achieve maximum benefit from these advances, carefully designed clinical studies with an accrual of hundreds or thousands of patients are probably needed. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:131 / 140
页数:10
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