Impact of cancer predisposition and radiosensitivity on the population risk of radiation-induced cancers

K. Sankaranarayanan et R. Chakraborty, Impact of cancer predisposition and radiosensitivity on the population risk of radiation-induced cancers, RADIAT RES, 156(5), 2001, pp. 648-656
Citations number
Categorie Soggetti
Experimental Biology
Journal title
ISSN journal
0033-7587 → ACNP
Year of publication
648 - 656
SICI code
This paper provides a brief overview of the current evidence for cancer pre disposition and for an increased sensitivity of individuals carrying such p redisposing mutations to cancers induced by ionizing radiations. We also di scuss the use of a Mendelian one-locus, two-allele autosomal dominant model for predicting the impact of cancer predisposition and increased radiosens itivity on the risk of radiation-induced cancers in the population and in r elatives of affected individuals using breast cancer due to BRCA1 mutations as an example. The main conclusions are the following: (1) The relative ri sk ratio of the risks of radiation-induced cancer in a heterogeneous popula tion which has subgroups of normal and cancer-predisposed individuals to th e risks in a homogeneous population (i.e., one which does not have these su bgroups) increases with increasing dose; however, the dose dependence of th e RR decreases at higher doses because of the fact that at high doses, the radiation risk to a homogeneous population will already be high. (2) The at tributable risk (the proportion of cancers attributable to increased cancer susceptibility and increased radiosensitivity) follows a similar pattern. (3) When the proportion of cancers due to the susceptible genotypes is smal l (< 10%), as is likely to be the case for breast cancers in non-Ashkenazi Jewish women, the increases in risk ratios and attributable risks are small , and become marked only when there are very large increases in cancer susc eptibility (> 1000-fold) and radiosensitivity (> 100-fold) in the susceptib le group. (4) When the proportion of cancers due to the susceptible genotyp es is appreciable (greater than or equal to 10%), as may be the case for br east cancers in Ashkenazi Jewish women, there may be significant increases in the risk ratios and attributable risk for comparatively moderate increas es in cancer susceptibility (> 10-fold) and radiosensitivity (> 100-fold) i n the susceptible subpopulation. (5) The ratio of the risk of radiation-ind uced cancer in relatives to that in unrelated individuals in the population increases with the biological relatedness of the relative, being higher fo r close than for distant relatives; however, even when the mutant BRCA1 gen e frequency and the proportion of breast cancers due to these mutations are high, as in Ashkenazi Jewish women, for values of predisposition strength and radiosensitivity differential < 10, the increase in breast cancer risks is only marginal, even for first-degree relatives. (C) 2001 by Radiation R esearch Society.