Mutagen sensitivity has high heritability: evidence from a twin study.
Despite numerous studies showing that mutagen sensitivity is a cancer predisposition factor, the heritability of mutagen sensitivity has not been clearly established. In this report, we used a classic twin study design to examine the role of genetic and environmental factors on the mutagen sensitivity phenotype. Mutagen sensitivity was measured in peripheral blood lymphocytes from 460 individuals [148 pairs of monozygotic (MZ) twins, 57 pairs of dizygotic (DZ) twins, and 50 siblings]. The intraclass correlation coefficients were all significantly higher in MZ twins than in dizygotes (DZ pairs and MZ-sibling pairs combined) for sensitivity to four different mutagen challenges. Applying biometric genetic modeling, we calculated a genetic heritability of 40.7%, 48.0%, 62.5%, and 58.8% for bleomycin, benzo[a]pyrene diol epoxide, gamma-radiation, and 4-nitroquinoline-1-oxide sensitivity, respectively. This study provides the strongest and most direct evidence that mutagen sensitivity is highly heritable, thereby validating the use of mutagen sensitivity as a cancer susceptibility factor.
Wu
Xifeng
X
Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. xwu@mdanderson.org
Spitz
Margaret R
MR
Amos
Christopher I
CI
Lin
Jie
J
Shao
Lina
L
Gu
Jian
J
de Andrade
Mariza
M
Benowitz
Neal L
NL
Shields
Peter G
PG
Swan
Gary E
GE
D020022:Genetic Predisposition to Disease; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology*; D009369:Neoplasms / Q000139:chemically induced / Q000235:genetics*; D014427:Twins / Q000097:blood / Q000187:drug effects* / Q000235:genetics
D009153:Mutagens