TY - JOUR
T1 - Mutagen sensitivity has high heritability
T2 - Evidence from a twin study
AU - Wu, Xifeng
AU - Spitz, Margaret R.
AU - Amos, Christopher I.
AU - Lin, Jie
AU - Shao, Lina
AU - Gu, Jian
AU - De Andrade, Mariza
AU - Benowitz, Neal L.
AU - Shields, Peter G.
AU - Swan, Gary E.
PY - 2006/6/15
Y1 - 2006/6/15
N2 - 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, γ-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.
AB - 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, γ-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.
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U2 - 10.1158/0008-5472.CAN-06-1007
DO - 10.1158/0008-5472.CAN-06-1007
M3 - Article
C2 - 16778168
AN - SCOPUS:33745728456
SN - 0008-5472
VL - 66
SP - 5993
EP - 5996
JO - Cancer research
JF - Cancer research
IS - 12
ER -