Cancer:
Breast
lung
Carcinogenesis.
2006 Apr 18; [Epub ahead of print] Int J Oncol.
2006 May;28(5):1217-23. Mol Cell.
2006 Mar 17;21(6):837-48.
Genetic variants of the
ADPRT, XRCC1, and APE1 genes and risk of cutaneous
melanoma.
Li
C, Liu
Z, Wang
LE, Strom
SS, Lee
JE, Gershenwald JE, Ross
MI, Mansfield
PF, Cormier
JN, Prieto VG, Duvic M, Grimm
EA, Wei Q.
Department of Epidemiology, The University of
Sunlight causes various kinds of DNA damage, including oxidative lesions
that are removed effectively by the base excision repair (BER) pathway, in
which ADPRT, XRCC1, and APE1 play a key role. However, genetic variation in
these genes may alter their functions. We hypothesized that ADPRT, XRCC1,
and APE1 polymorphisms are associated with risk of cutaneous
melanoma (CM). In a hospital-based case-control study of 602 CM patients
and 603 cancer-free control subjects frequency matched on age, sex, and
ethnicity, we genotyped for three non-synonymous single-nucleotide
polymorphisms (SNPs) (i.e., the ADPRT Val762Ala,
XRCC1 Arg399Gln, and APE1Asp148Glu) and assessed their associations with
risk of CM. We found no significant difference in the allele frequencies
between cases and controls for any of these three SNPs.
However, we found that, compared with the APE1 Asp/Asp genotype, a
significantly decreased risk of CM was associated with the APE1 Asp/Glu (adjusted odds ratio [OR] = 0.60, 95% confidence
interval [CI] = 0.41-0.86), Glu/Glu (OR = 0.58,
95% CI = 0.38-0.88) and combined APE1 Asp/Glu+Glu/Glu
(OR = 0.59, 95% CI = 0.42-0.83) genotypes, but not for other XRCC1 variant
genotypes. Moreover, there was evidence for a possible gene-gene
interaction between XRCC1 and APE1 variants in the association with risk of
CM (P = 0.030). We conclude that the APE1 Glu
variant may have an effect or interact with XRCC1 in the etiology of CM or
in linkage disequilibrium with other untyped
protective alleles. Larger studies with more SNPs
in the BER genes are needed to verify these findings.
PMID: 16621887 [PubMed - as supplied by publisher]
Association of XRCC1
gene polymorphisms with the susceptibility and chromosomal aberration of
testicular germ cell tumors.
Tsuchiya
N, Mishina M, Narita
S, Kumazawa T, Inoue
T, Horikawa Y, Kakinuma H, Yuasa
T, Matsuura
S, Satoh
S, Ogawa
O, Habuchi T.
Department of Urology,
It is known that many genomic and genetic alterations caused by aging or
environmental factors are responsible for cancer development and
progression. XRCC1 is involved in the repair of DNA single-strand breaks
formed by exposure to ionizing radiation and alkylating
agents. The objective of this study was to investigate the association of
genomic alterations and the susceptibility of testicular germ cell tumors
with XRCC1 polymorphisms. Two polymorphisms of XRCC1, Arg194Trp and
Arg399Gln, were genotyped in 83 patients with testicular germ cell tumors
(TGCT) and 87 male controls. Allelic imbalances (AI) were evaluated using 4
microsatellite markers in a subgroup of 50 patients.
Patients with at least one Gln allele of the
Arg399Gln polymorphism had an increased risk of TGCT than those with the Arg/Arg genotype (aOR=1.775,
95% CI=1.045-3.016, P=0.034). Furthermore, the increased risk associated
with the Gln allele against the Arg homozygote was more strongly observed in patients
with pure seminoma (aOR=2.242,
95% CI=1.149-4.374, P=0.018) or with metastasis (aOR=2.481,
95% CI=1.267-4.862, P=0.008). In the Arg194Trp polymorphism, there was no
significant difference in the genotype distribution between TGCT patients
and the controls. In AI analysis, the frequency of AI was significantly
higher in tumors with at least one Gln allele
than those with the Arg/Arg genotype in D13S317
(P=0.010) and in a combination of 4 markers (0.51+/-0.32 vs 0.32+/-28, P=0.028). Our results suggest that the Gln allele of the XRCC1 Arg399Gln polymorphism may
genetically modify the development and progression of TGCT through genomic
instability.
PMID: 16596238 [PubMed - in process]
Condensin I interacts with the PARP-1-XRCC1 complex and
functions in DNA single-strand break repair.
Heale JT, Ball
AR Jr, Schmiesing JA, Kim
JS, Kong
X, Zhou
S, Hudson
DF, Earnshaw WC, Yokomori K.
Department of Biological Chemistry,
Condensins are essential protein complexes
critical for mitotic chromosome organization. Little is known about the
function of condensins during interphase,
particularly in mammalian cells. Here we report the interphase-specific
interaction between condensin I and the DNA
nick-sensor poly(ADP-ribose) polymerase 1
(PARP-1). We show that the association between condensin
I, PARP-1, and the base excision repair (BER) factor XRCC1 increases
dramatically upon single-strand break damage (SSB) induction.
Damage-specific association of condensin I with
the BER factors flap endonuclease 1 (FEN-1) and
DNA polymerase delta/epsilon was also observed, suggesting that condensin I is recruited to interact with BER factors
at damage sites. Consistent with this, DNA damage rapidly stimulates the
chromatin association of PARP-1, condensin I, and
XRCC1. Furthermore, depletion of condensin in
vivo compromises SSB but not double-strand break (DSB) repair. Our results
identify a SSB-specific response of condensin I through PARP-1 and demonstrate a role for condensin in SSB repair.
PMID: 16543152 [PubMed - indexed for MEDLINE]