Download Gene Section ERCC1 (excision repair complementing defective repair in Chinese hamster)

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Gene Section
Mini Review
ERCC1 (excision repair complementing defective
repair in Chinese hamster)
Ulla Vogel
National Research Centre for the Working Environment, Lerso Parkalle 105, DK-2100 Copenhagen O,
Denmark
Published in Atlas Database: December 2006
Online updated version: http://AtlasGeneticsOncology.org/Genes/ERCC1ID40481ch19q13.html
DOI: 10.4267/2042/38403
This work is licensed under a Creative Commons Attribution-Non-commercial-No Derivative Works 2.0 France Licence.
© 2007 Atlas of Genetics and Cytogenetics in Oncology and Haematology
heterodimer with XPF (also called ERCC4) to form the
endonuclease which makes the 5’ incision during
nucleotide excision repair.
ERCC1 mRNA levels in lymphocytes correlate
positively with DNA repair capacity measured by host
cell reactivation. ERCC1 mRNA levels correlate
closely with XPD, OGG1 and RAI mRNA levels in
lymphocytes.
In case-control studies of lung cancer patients, lung
cancer patients were shown to have lower mRNA
levels and lower DNA repair capacity than healthy
controls. This was also found in a case-control study of
head and neck cancer. However, in a prospective study
of lung cancer, persons, who were later diagnosed with
lung cancer did not have a lower ERCC1 mRNA level
than those who did not get lung cancer, indicating that
the low ERCC1 expression level observed in cancer
patients may be a result of the disease rather than a
cause.
ERCC1 expression seems to be inducible at least at the
mRNA level. Thus, the expression of ERCC1 in human
lymphocytes correlated with increased solar influx
indicating that UV irradiation may induce ERCC1
expression. In mice, X-ray irradiation lead to increased
ERCC1 expression in lung tissue, and ingestion of
diesel exhaust particles increased ERCC1 expression in
liver. This indicates that ERCC1 expression is
inducible, and thus that ERCC1 expression levels may
rather be a biomarker of the internal dose of DNA
damage than a biomarker of DNA repair capacity or a
mix of the two.
Identity
Hugo: ERCC1
Location: 19q13.32.
DNA/RNA
Description
14 305 bp and 10 exons.
Transcription
1,101 bps.
Protein
Description
297 amino acids.
Expression
ERCC1 is expressed at higher levels in tumor tissue
compared to normal tissue and the expression shows
more inter-individual variation among cancer patients
than among healthy individuals. ERCC1 expression
and ERCC1 protein levels in tumor tissue may predict
response to chemotherapy. Thus, non-small cell lung
cancer patients with undetectable ERCC1 protein levels
in tumor tissue had a longer survival after cisplatinbased adjuvant chemotherapy than patients with
detectable ERCC1 protein levels. However, high
ERCC1 protein levels were associated with increased
survival among patients who were not treated with
chemotherapy.
Function
Mutations
ERCC1 was originally identified as a gene that
complemented a certain DNA repair defective Chinese
Hamster Ovary cells (CHO) UV20. ERCC1 forms a
Note: One of the most frequently studied
polymorphisms in ERCC1 is ERCC1 Asn118Asn
(rs11615). Homozygous carriers of the haplotype
Atlas Genet Cytogenet Oncol Haematol. 2007;11(2)
93
ERCC1 (excision repair complementing defective repair in Chinese hamster)
ERCC1 Asn118AsnA, ASE-1 G-21AG, PPP1R13L
IVS1 A4364GA have been shown to be at increased
risk of breast cancer and lung cancer.
The ERCC1 Asn118Asn polymorphism was found not
to correlate with mRNA levels.
ERCC1 C8092A (rs3212986) was found to interact
with smoking in relation to risk of lung cancer in a
large case-control study. ERCC1 C8092A was found
not to correlate with mRNA levels in peripheral blood
cells.
Colorectal cancer, small cell lung
cancer, and non small cell lung cancer
Disease
Carriers of the variant allele of ERCC1 Asn118Asn
were found to have a worse prognosis of colorectal
cancer, small cell lung cancer and non-small cell lung
cancer, whereas no association with risk of colorectal
cancer has been found.
References
Implicated in
Thompson LH, Mooney CL, Burkhart-Schultz K, Carrano AV,
Siciliano MJ. Correction of a nucleotide-excision-repair
mutation by human chromosome 19 in hamster-human hybrid
cells. Somat Cell Mol Genet 1985;11(1):87-92.
Breast cancer
Prognosis
Thus, women who were homozygous carriers of the
haplotype had a 9.5-fold higher risk of breast cancer
before 55 years of age than women who were not
homozygous carriers. Older women and heterozygous
carriers were not at an increased risk of breast cancer.
Dabholkar M, Bostick-Bruton F, Weber C, Bohr VA, Egwuagu
C, Reed E. ERCC1 and ERCC2 expression in malignant
tissues from ovarian cancer patients. J Natl Cancer Inst
1992;19:1512-1517.
Dabholkar M, Bostick-Bruton F, Weber C, Egwuagu C, Bohr
VA, Reed E. Expression of excision repair genes in nonmalignant bone marrow from cancer patients. Mutation
Research 1993;293:151-160.
Lung cancer
Dabholkar M, Vionnet J, Bostick-Bruton F, Yu JJ, Reed E.
Messenger RNA levels of XPAC and ERCC1 in ovarian cancer
tissue
correlate
with
response
to
platinum-based
chemotherapy. J Clin Invest 1994;94:703-708.
Disease
Homozygous carriers of the haplotype were found to be
at 4.9-fold increased risk of lung cancer in the age
interval 50-55 years. The association was stronger
among women than among men, although the
difference was not statistically significant. In
subsequent study including more cases and a larger
comparison group, a statistically significant difference
between genders was found. Furthermore, it was found
that the haplotype interacts with smoking intensity.
Thus, among women, who were carriers of the
haplotype, additional smoking at high smoking
intensity (>20 cigarettes/day) was associated with
increased lung cancer risk. This was not seen among
women who were not homozygous carriers of the
haplotype or among men.
The haplotype was not associated with risk of testis
cancer or with risk of colorectal adenomas or colorectal
cancer. Furthermore, the haplotype was not associated
with risk of basal cell carcinoma among older persons
(>60 years).These results indicate that the haplotype
may be associated with risk of cancer primarily among
young and middle aged persons and that it may be
specific for women.
Matsunaga T, Mu D, Park CH, Reardon JT, Sancar A. Human
DNA repair excision nuclease. Analysis of the roles of the
subunits involved in dual incisions by using anti-XPG and antiERCC1 antibodies. J Biol Chem 1995;270(35):20862-20869.
Park CH, Bessho T, Matsunaga T, Sancar A. Purification and
characterization of the XPF-ERCC1 complex of human DNA
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levels of nucleotide excision repair genes in lung cancer: a
case-control analysis. Carcinogenesis 2000;21(8):1527-1530.
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inconsistency between effect of over-expression of five NER
genes and the correlation to mRNA levels in primary
lymphocytes. Mutat Res 2000;461(3):197-210.
Vogel U, Møller P, Dragsted L, Loft S, Pedersen A, Sandstrom
B. Inter-individual variation, seasonal variation and close
correlation of OGG1 and ERCC1 mRNA levels in full blood
from healthy volunteers. Carcinogenesis 2002;23(9):15051509.
Dybdahl M, Risom L, Moller P, Autrup H, Wallin H, Vogel U,
Bornholdt J, Daneshvar B, Dragsted LO, Weimann A, Poulsen
HE, Loft S. DNA adduct formation and oxidative stress in colon
and liver of Big Blue rats after dietary exposure to diesel
particles. Carcinogenesis 2003;24(11):1759-1766.
Leukemia and bladder cancer
Disease
The variant allele of ERCC1 Asn118Asn has also been
combined with the polymorphisms XPD Asp312Asn
and XPD Lys752Gln in haplotype analysis. Here, the
haplotype GAT was associated with increased risk of
leukemia and bladder cancer among non-smokers and
the ACC haplotype was associated with lowered risk of
bladder cancer.
Atlas Genet Cytogenet Oncol Haematol. 2007;11(2)
Vogel U
Nexo BA, Vogel U, Olsen A, Ketelsen T, Bukowy Z, Thomsen
BL. Wallin H, Overvad K, Tjonneland A. A specific haplotype of
single nucleotide polymorphisms on chromosome 19q13.2-3
encompassing the gene RAI is indicative of postmenopausal
breast cancer before age 55. Carcinogenesis 2003;24(5):899904.
Park DJ, Zhang W, Stoehlmacher J, Tsao-Wei D, Groshen S,
Gil J, Yun J, Sones E, Mallik N, Lenz HJ. ERCC1 gene
polymorphism as a predictor for clinical outcome in advanced
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ERCC1 (excision repair complementing defective repair in Chinese hamster)
colorectal cancer patients treated with platinum-based
chemotherapy. Clin Adv Hematol Oncol 2003;1(3):162-166.
Trichopoulou A, Palli D, Krogh V, Tumino R, Panico S, Buenode-Mesquita HB, Peeters PH, Lund E, Pera G, Martinez C,
Dorronsoro M, Barricarte A, Tormo MJ, Quiros JR, Day NE,
Key TJ, Saracci R, Kaaks R, Riboli E, Vineis P. DNA repair
polymorphisms and cancer risk in non-smokers in a cohort
study. Carcinogenesis 2006;27(5):997-1007.
Risom L, Dybdahl M, Bornholdt J, Vogel U, Wallin H, Moller P,
Loft S. Oxidative DNA damage and defence gene expression
in the mouse lung after short-term exposure to diesel exhaust
particles by inhalation. Carcinogenesis 2003;24(11):18471852.
Moreno V, Gemignani F, Landi S, Gioia-Patricola L, Chabrier
A, Blanco I, Gonzalez S, Guino E, Capella G, Canzian F.
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repair: risk and prognosis of colorectal cancer. Clin Cancer
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Isla D, Sarries C, Rosell R, Alonso G, Domine M, Taron M,
Lopez-Vivanco G, Camps C, Botia M, Nunez L, SanchezRonco M, Sanchez JJ, Lopez-Brea M, Barneto I, Paredes A,
Medina B, Artal A, Lianes P. Single nucleotide polymorphisms
and outcome in docetaxel-cisplatin-treated advanced nonsmall-cell lung cancer. Ann Oncol 2004;15(8):1194-1203.
Olaussen KA, Dunant A, Fouret P, Brambilla E, Andre F,
Haddad V, Taranchon E, Filipits M, Pirker R, Popper HH,
Stahel R, Sabatier L, Pignon JP, Tursz T, Le Chevalier T, Soria
JC. DNA repair by ERCC1 in non-small-cell lung cancer and
cisplatin-based adjuvant chemotherapy. N Engl J Med
2006;355(10):983-991.
Ryu JS, Hong YC, Han HS, Lee JE, Kim S, Park YM, Kim YC,
Hwang TS. Association between polymorphisms of ERCC1
and XPD and survival in non-small-cell lung cancer patients
treated with cisplatin combination chemotherapy. Lung Cancer
2004;44(3):311-316.
Saebo M, Skjelbred CF, Nexo BA, Wallin H, Hansteen IL,
Vogel U, Kure EH. Increased mRNA expression levels of
ERCC1, OGG1 and RAI in colorectal adenomas and
carcinomas. BMC Cancer 2006;6:208.
Vogel U, Laros I, Jacobsen NR, Thomsen BL, Bak H, Olsen A,
Bukowy Z, Wallin H, Overvad K, Tjonneland A, Nexo BA,
Raaschou-Nielsen O. Two regions in chromosome 19 q13.2-3
are associated with risk of lung cancer. Mutation Research
2004;546:65-74.
Skjelbred CF, Saebo M, Nexo BA, Wallin H, Hansteen IL,
Vogel U, Kure EH. Effects of polymorphisms in ERCC1, ASE-1
and RAI on the risk of colorectal carcinomas and adenomas: a
case control study. BMC Cancer 2006;6:175.
Laska MJ, Nexo BA, Vistisen K, Poulsen HE, Loft S, Vogel U.
Polymorphisms in RAI and in genes of nucleotide and base
excision repair are not associated with risk of testicular cancer.
Cancer Lett 2005;225(2):245-251.
Vogel U, Nexo BA, Tjonneland A, Wallin H, Hertel O,
Raaschou-Nielsen O. ERCC1, XPD and RAI mRNA levels in
lymphocytes are not associated with lung cancer risk in a
prospective study of Danes. Mutat Res 2006a;593(1-2):88-96.
Matullo G, Guarrera S, Sacerdote C, Polidoro S, Davico L,
Gamberini S, Karagas M, Casetta G, Rolle L, Piazza A, Vineis
P. Polymorphisms/haplotypes in DNA repair genes and
smoking: a bladder cancer case-control study. Cancer
Epidemiol Biomarkers Prev 2005;14(11 Pt 1):2569-2578.
Vogel U, Sorensen M, Hansen RD, Tjonneland A, Overvad K,
Wallin H, Nexo BA, Raaschou-Nielsen O. Gene-environment
interactions between smoking and a haplotype of RAI, ASE-1
and ERCC1 polymorphisms among women in relation to risk of
lung cancer in a population-based study. Cancer Lett
2006b;247:159-165.
Vogel U, Olsen A, Wallin H, Overvad K, Tjonneland A, Nexo
BA. Effect of polymorphisms in XPD, RAI, ASE-1 and ERCC1
on the risk of basal cell carcinoma among Caucasians after
age 50. Cancer Detect Prev 2005;29(3):209-214.
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Effects of ERCC1 expression in peripheral blood on the risk of
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Christiani DC. Gene-Smoking Interaction Associations for the
ERCC1 Polymorphisms in the Risk of Lung Cancer. Cancer
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This article should be referenced as such:
Vogel U. ERCC1 (excision repair complementing defective
repair in Chinese hamster). Atlas Genet Cytogenet Oncol
Haematol.2007;11(2):93-95.
Matullo G, Dunning AM, Guarrera S, Baynes C, Polidoro S,
Garte S, Autrup H, Malaveille C, Peluso M, Airoldi L, Veglia F,
Gormally E, Hoek G, Krzyzanowski M, Overvad K, RaaschouNielsen O, Clavel-Chapelon F, Linseisen J, Boeing H,
Atlas Genet Cytogenet Oncol Haematol. 2007;11(2)
Vogel U
95