Polymorphisms of the DNA repair genes XRCC1 and ERCC4 are not associated with smoking- and drinking-dependent larynx cancer in a polish population
Aim of this article is to investigate the association between the genotypes of the XRCC1-Arg399Gln (rs25487) and ERCC4-Arg415Gln (rs1800067) polymorphisms and smoking- and drinking-related larynx cancer in a Polish population.
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| Опубліковано в: : | Experimental Oncology |
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| Дата: | 2011 |
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
2011
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| Цитувати: | Polymorphisms of the DNA repair genes XRCC1 and ERCC4 are not associated with smoking- and drinking-dependent larynx cancer in a polish population / R. Krupa, J. Kasznicki, M. Gajecka, M. Rydzanicz, K. Kiwerska, D. Kaczmarczyk, J. Olszewski, K. Szyfter, J. Blasiak, A. Morawiec-Sztandera // Experimental Oncology. — 2011. — Т. 33, № 1. — С. 55-56. — Біліогр.: 8 назв. — англ. |
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Krupa, R. Kasznicki, J. Gajecka, M. Rydzanicz, M. Kiwerska, K. Kaczmarczyk, D. Olszewski, J. Szyfter, K. Blasiak, J. Morawiec-Sztandera, A. 2012-04-16T21:09:16Z 2012-04-16T21:09:16Z 2011 Polymorphisms of the DNA repair genes XRCC1 and ERCC4 are not associated with smoking- and drinking-dependent larynx cancer in a polish population / R. Krupa, J. Kasznicki, M. Gajecka, M. Rydzanicz, K. Kiwerska, D. Kaczmarczyk, J. Olszewski, K. Szyfter, J. Blasiak, A. Morawiec-Sztandera // Experimental Oncology. — 2011. — Т. 33, № 1. — С. 55-56. — Біліогр.: 8 назв. — англ. 1812-9269 https://nasplib.isofts.kiev.ua/handle/123456789/32320 Aim of this article is to investigate the association between the genotypes of the XRCC1-Arg399Gln (rs25487) and ERCC4-Arg415Gln (rs1800067) polymorphisms and smoking- and drinking-related larynx cancer in a Polish population. This work was supported by the grants N403 2955 33 from the Ministry of Science and Higher Education and 505/376 from the University of Lodz, Poland. en Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України Experimental Oncology Short communications Polymorphisms of the DNA repair genes XRCC1 and ERCC4 are not associated with smoking- and drinking-dependent larynx cancer in a polish population Article published earlier |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine |
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DSpace DC |
| title |
Polymorphisms of the DNA repair genes XRCC1 and ERCC4 are not associated with smoking- and drinking-dependent larynx cancer in a polish population |
| spellingShingle |
Polymorphisms of the DNA repair genes XRCC1 and ERCC4 are not associated with smoking- and drinking-dependent larynx cancer in a polish population Krupa, R. Kasznicki, J. Gajecka, M. Rydzanicz, M. Kiwerska, K. Kaczmarczyk, D. Olszewski, J. Szyfter, K. Blasiak, J. Morawiec-Sztandera, A. Short communications |
| title_short |
Polymorphisms of the DNA repair genes XRCC1 and ERCC4 are not associated with smoking- and drinking-dependent larynx cancer in a polish population |
| title_full |
Polymorphisms of the DNA repair genes XRCC1 and ERCC4 are not associated with smoking- and drinking-dependent larynx cancer in a polish population |
| title_fullStr |
Polymorphisms of the DNA repair genes XRCC1 and ERCC4 are not associated with smoking- and drinking-dependent larynx cancer in a polish population |
| title_full_unstemmed |
Polymorphisms of the DNA repair genes XRCC1 and ERCC4 are not associated with smoking- and drinking-dependent larynx cancer in a polish population |
| title_sort |
polymorphisms of the dna repair genes xrcc1 and ercc4 are not associated with smoking- and drinking-dependent larynx cancer in a polish population |
| author |
Krupa, R. Kasznicki, J. Gajecka, M. Rydzanicz, M. Kiwerska, K. Kaczmarczyk, D. Olszewski, J. Szyfter, K. Blasiak, J. Morawiec-Sztandera, A. |
| author_facet |
Krupa, R. Kasznicki, J. Gajecka, M. Rydzanicz, M. Kiwerska, K. Kaczmarczyk, D. Olszewski, J. Szyfter, K. Blasiak, J. Morawiec-Sztandera, A. |
| topic |
Short communications |
| topic_facet |
Short communications |
| publishDate |
2011 |
| language |
English |
| container_title |
Experimental Oncology |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| format |
Article |
| description |
Aim of this article is to investigate the association between the genotypes of the XRCC1-Arg399Gln (rs25487) and ERCC4-Arg415Gln (rs1800067) polymorphisms and smoking- and drinking-related larynx cancer in a Polish population.
|
| issn |
1812-9269 |
| url |
https://nasplib.isofts.kiev.ua/handle/123456789/32320 |
| citation_txt |
Polymorphisms of the DNA repair genes XRCC1 and ERCC4 are not associated with smoking- and drinking-dependent larynx cancer in a polish population / R. Krupa, J. Kasznicki, M. Gajecka, M. Rydzanicz, K. Kiwerska, D. Kaczmarczyk, J. Olszewski, K. Szyfter, J. Blasiak, A. Morawiec-Sztandera // Experimental Oncology. — 2011. — Т. 33, № 1. — С. 55-56. — Біліогр.: 8 назв. — англ. |
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2025-11-25T22:49:42Z |
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2025-11-25T22:49:42Z |
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| fulltext |
Experimental Oncology ��� ������ ���� ��arc����� ������ ���� ��arc�� ��arc�� ��
POLYMORPHISMS OF THE DNA REPAIR GENES XRCC1 AND
ERCC4 ARE NOT ASSOCIATED WITH SMOKING- AND DRINKING-
DEPENDENT LARYNX CANCER IN A POLISH POPULATION
R. Krupa1, J. Kasznicki2, M. Gajęcka3, M. Rydzanicz3, K. Kiwerska3, D. Kaczmarczyk4, J. Olszewski5,
K. Szyfter3,6, J. Blasiak1,*, A. Morawiec-Sztandera4
1Department of Molecular Genetics, University of Lodz, Lodz 90-236, Poland
2Department of Internal Medicine, Diabetology and Clinical Pharmacology, Medical University of Lodz,
Lodz 90-419, Poland
3Institute of Human Genetics, Polish Academy of Sciences, Poznan 60-479, Poland
4Department of Head and Neck Cancer, Medical University of Lodz, Lodz 90-419, Poland
5Department of Otolaryngology, Medical University of Lodz, Lodz 90-419, Poland
6Department of Otolaryngology, Medical University of Poznan, Poznan 61-701, Poland
Background: Tobacco smoking and alcohol drinking generate oxidative DNA damage and may contribute to larynx carcinogenesis.
The X-ray repair cross complementing 1 (XRCC1) and excision repair cross-complementing rodent repair deficiency, complementa-
tion group 4 (ERCC4(XPF)) genes are important components of DNA excision repair systems, which repair DNA damage induced
by various factors, including tobacco smoking and alcohol. Aim: To investigate the association between the genotypes of the XRCC1-
Arg399Gln (rs25487) and ERCC4-Arg415Gln (rs1800067) polymorphisms and smoking- and drinking-related larynx cancer in a Polish
population. Methods: The polymorphisms were determined by PCR-RFLP method in 253 patients with squamous cell carcinoma of the
larynx and 253 sex- and age-matched controls. Results: We did not find any association between the investigated polymorphisms and
larynx carcinoma, dependent on either smoking or drinking status. No association was found between these polymorphisms and larynx
cancer grade, stage or age at diagnosis. Conclusions: The results indicated that Arg399Gln polymorphism of XRCC1 gene and Arg-
415Gln polymorphism of ERCC4 gene may not be associated with smoking- and drinking-related larynx cancer in Polish population.
Key Words: smoking, alcohol consumption, XRCC1, ERCC4, larynx cancer, gene polymorphism.
Tobacco smoking and alco�ol exposure are well
known risk factors in t�e development of squamous cell
carcinoma of t�e larynx. It was suggested t�at single
nucleotide polymorp�isms �SNPs� in t�e DNA repair
genes may alter t�e ability of cells to repair damaged
DNA� and initiate malignant transformation. X-ray repair
cross-complementing � �XRCC1� gene coding for t�e
XRCC�� one of a key protein of base excision repair �BER�
pat�way. Excision repair cross-complementing rodent
repair deficiency� complementation group 4 �ERCC4/
XPF) gene coding for t�e ERCC4/XPF protein one of es-
sential parts of nucleotide excision repair �NER� pat�way.
A G → A substitution at �8��� of t�e XRCC1 gene� exon
��� producing an Arg to Gln c�ange in codon �99 �t�e
Arg�99Gln polymorp�ism� �as been linked to slig�tly
�marginally statistically significant� increased risk of la-
ryngeal carcinoma among Caucasians [�]. T�e ERCC4/
XPF G��44A polymorp�ism is a G-to-A c�ange in t�e
exon 8 �Arg4��Gln� rs�8����7� t�at results in a c�ange
from arginine to glutamine at 4�� codon. T�is polymor-
p�ism �as been reported to be associated wit� an in-
creased risk for breast cancer [�].
In t�is paper� we �ave used a �ospital-based case-
control study in Poland to assess t�e potential association
of t�e XRCC1-Arg�99Gln and ERCC4-Arg4��Gln SNPs
wit� t�e development and clinical pat�ological parameters
of larynx cancer.
Patients. Blood samples were obtained from ��� pa-Blood samples were obtained from ��� pa-
tients: �94 men and �9 women wit� larynx cancer �squa-
mous cell carcinoma� treated in t�e Department of Head
and Neck Cancer� �edical University of Lodz� Lodz�
Poland and Department of Otolaryngology� �edical
University of Poznan� Poznan� Poland in ��������9 and
��� cancer-free age and sex matc�ed controls. T�e
patients ranged in age from 48 to 8� years �median age
�� years�. Grade of differentiation �G� was evaluated in all
cases �according to World Healt� Organization criteria�.
T�ere were ��8 cases of � grade� ��4 cases of � grade
and �� of � grade in total. According to TN� staging t�ere
were �� cases of stage I� �� cases of stage II� ��� cases
of stage III� 4� cases of stage IVA and � of stage IVB. T�e
study was approved by Et�ic Committee of �edical
University of Lodz and �edical University of Poznan� and
eac� patient gave a written consent.
DNA isolation. Perip�eral blood lymp�ocytes
�PBLs� were isolated by centrifugation in a density
gradient of Histopaque-��77 ��� min� �8�g�. T�e pellet
containing PBLs was resuspended in Tris-EDTA buffer�
pH 8� to give about ��� x��� cells/ml. Genomic DNA
was extracted from PBLs by p�enol/c�loroform extrac-
Received: January 11, 2011.
*Correspondence: Fax: +48426354484
E-mail: jblasiak@biol.uni.lodz.pl
Abbreviations used: BER – base excision repair; ERCC4 (XPF) –
excision repair cross-complementing rodent repair deficiency,
complementation group 4 gene; NER – nucleotide excision
repair; OR – odds ratio; PBLs – peripheral blood lymphocytes;
PCR – RFLP – polymerase chain reaction - restriction fragment
length polymorphism; SNPs – single nucleotide polymorphisms;
XRCC1 – the X-ray repair cross complementing 1 gene.
Exp Oncol ����
��� �� �����
�� Experimental Oncology ��� ������ ���� ��arc��
tion and proteinase K digestion. T�e final samples were
kept in Tris-EDTA buffer� pH 8� at ��� °C until use.
Genotype determination. T�e PCR — restriction
fragment lengt� polymorp�ism met�od �PCR � RFLP�
was used to detect t�e genotypes of t�e Arg�99Gln
polymorp�ism of XRCC1 gene and t�e Arg4��Gln poly-
morp�ism of ERCC4 gene as described previously [�� 4].
Data analysis. For eac� genotype� deviation of t�e
frequencies in t�e controls from t�ose expected under
Hardy — Weinberg equilibrium was assessed using t�e
standard χ�-test. Genotype frequencies in cases and
controls were compared by χ� or Fis�er’s exact tests.
T�e genotype-specific risks were estimated as odds
ratios �ORs� by unconditional logistic regression. Wild
type Arg/Arg genotype was used as t�e reference.
Because of small number of Gln/Gln variant genotypes
of bot� polymorp�isms odds ratios were calculated
for Gln allele carriers �Arg/Gln + Gln/Gln genotypes�
p-values < �.�� were considered to be significant.
All statistical analyses were performed wit� Sigma-
Stat� ver. 8.� �Systat Software Inc� San Jose� CA� USA�.
We s�owed previously t�at �eavy alco�ol drinking and
tobacco smoking increased significantly t�e risk of laryn-
geal carcinoma independently of any genetic variation
�OR = �8; p < �.���� for smoking and drinking �eavily�
[�]. Tobacco smoke contains many kinds of carcinogens
t�at can cause DNA lesions� and variations in repair of to-
bacco carcinogen-induced DNA lesions may contribute
to t�e variation in susceptibility to cancer [�].
It was suggested t�at SNP at codon �99 of t�e
XRCC1 gene may alter t�e ability of XRCC1 to repair
damaged DNA [7]. It was also s�own t�at t�e �99Gln �o-
mozygote genotype was associated wit� increased levels
of bulky-DNA adducts in leucocytes of non-smokers [8].
From t�e PCR analysis� ��� larynx cancer patients
and ��� controls were divided into t�ree genotypes:
Arg/Arg� Arg/Gln and Gln/Gln for bot� gene polymor-
p�isms. Distributions of genotypes did not differ sig-
nificantly from t�ose predicted by t�e Hardy-Weinberg
equilibrium. T�ere were no significant differences
in t�e frequencies of bot� polymorp�isms genotypes
between patients and controls �p > �.���. Additionally�
odds ratio analysis did not s�ow any relation between
t�is polymorp�isms and larynx cancer �data not s�own�.
All ��� larynx cancer cases were stratified by grade
of differentiation and stage of disease. Grades � and
� were grouped toget�er for t�e purposes of statistical
analysis. T�ere were no significant differences between
distributions of genotypes in subgroups assigned to �is-
tological grades and TN� stages �data not s�own�.
To c�eck w�et�er DNA repair gene polymorp�isms
were associated wit� tobacco smoking� participants
were categorized into groups according to smoking
�abits �Table�. T�ere were no significant differences
inside t�ese groups in t�e Arg�99Gln and Arg4��Gln
polymorp�isms genotypes distribution �p > �.���. Ad-
ditionally� we did not find any association of investigated
polymorp�isms and drinking status �Table�. We did not
find any association of drinking and smoking status and
laryngeal cancer for carriers of bot� variant genotypes
of XRCC1 and ERCC4 genes �data not s�own�.
Our results indicated t�at Arg�99Gln polymor-
p�ism of XRCC1 gene and Arg4��Gln polymorp�ism
of ERCC4 gene may not be associated wit� smoking-
and drinking-related larynx cancer in Polis� population.
ACKNOWLEDGEMENTS
T�is work was supported by t�e grants
N4�� �9�� �� from t�e �inistry of Science and Hig�er
Education and ���/�7� from t�e University of Lodz� Poland.
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Copyright © Experimental Oncology, 2011
Table. Genotype distribution and odds ratio (OR) for Arg399Gln polymorphism of XRCC1 gene and Arg415Gln polymorphism of ERCC4 gene for laryngeal
cancer patients and controls
Arg399Gln - XRCC1, number of patients/controls Arg415Gln - ERCC4 number of patients/controls
Arg/Arg Arg/Gln Gln/Gln ORa /p Arg/Arg Arg/Gln Gln/Gln ORa /p
smokers
never 12/50 12/56 8/17 1.23/0.30 29/106 2/17 1/0 1.13/0.69
ever 33/30 46/33 22/13 0.83/0.30 88/70 11/6 2/0 1.07/0.80
moderate 17/12 17/15 7/4 0.81/0.30 37/28 4/3 0/0 1.06/0.85
heavy 31/13 36/9 12/1 0.76/0.19 67/20 9/3 3/0 0.98/0.95
drinkers
never 24/45 26/50 10/17 1.32/0.17 55/99 4/13 1/0 1.05/0.88
moderate 54/51 62/55 34/15 0.83/0.30 130/108 16/13 4/0 1.03/0.77
heavy 15/9 23/8 5/3 0.81/0.30 36/17 6/3 1/0 1.09/0.79
Note: a — odds ratio adjusted with age and sex; odds ratio calculated for Arg/Gln + Gln/Gln genotype carriers, Arg/Arg genotype served as the reference (OR = 1.00).
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