title: Potential risk of esophageal squamous cell carcinoma due to nucleotide excision repair XPA and XPC gene variants and their interaction among themselves and with environmental factors.
abstract: The association of nucleotide excision repair (NER) gene polymorphisms with esophageal squamous cell carcinoma (ESCC) is inconclusive. The aim of the current study was to assess the association of repair gene xeroderma pigmentosum A (XPA) (rs-1800975) and xeroderma pigmentosum C (XPC) (rs-2228000) polymorphisms with ESCC risk as well as modifying effects of environmental factors. The genotyping was done in 450 confirmed ESCC cases and equal number of individually matched controls by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) and direct sequencing methods. Conditional logistic regression models were used to assess the genotypic associations and interactions. A high ESCC risk was found in subjects who carried the homozygous minor allele of XPA (odds ratio (OR) = 3.57; 95 % confidence interval (CI) = 1.76-7.23), and the risk was higher when analysis was limited to participants who were ever smokers (OR = 4.22; 95 % CI = 2.01-8.88), lived in adobe houses (OR = 8.42; 95 % CI = 3.74-18.95), consumed large volumes of salt tea (OR = 7.42; 95 % CI = 3.30-16.69), or had a positive family history of cancer (FHC) (OR = 9.47; 95 % CI = 4.67-19.20). In case of XPC, a homozygous minor allele also showed strong association with ESCC risk (OR = 4.43; 95 % CI = 2.41-8.16). We again observed a very strong effect of the above environmental factors in elevating the risk of ESCC. Further, the variant genotypes of both genes in combination showed an increased risk towards ESCC (OR = 7.01; 95 % CI = 3.14-15.64) and such association was synergistically significant. Salt tea consumption showed an interaction with genotypes of XPA and XPC. However, an interaction with FHC was significant in the case of XPA genotype only. XPA and XPC genotypes are associated with an increased risk of ESCC, and such association was reasonably modulated by different exposures.
authors.affiliation: Department of Biochemistry, University of Kashmir, Srinagar, Jammu and Kashmir, India, 190006.
authors.forename: Rumaisa
authors.initials: R
authors.lastname: Rafiq
authors.affiliation: Department of Biochemistry, University of Kashmir, Srinagar, Jammu and Kashmir, India, 190006.
authors.forename: Gulzar Ahmad
authors.initials: GA
authors.lastname: Bhat
authors.affiliation: Department of Radiation Oncology, SK Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India, 190011.
authors.forename: Mohd Maqbool
authors.initials: MM
authors.lastname: Lone
authors.affiliation: Department of Biochemistry, University of Kashmir, Srinagar, Jammu and Kashmir, India, 190006.
authors.forename: Akbar
authors.initials: A
authors.lastname: Masood
authors.affiliation: Department of Biochemistry, University of Kashmir, Srinagar, Jammu and Kashmir, India, 190006. nazirramzan@uok.edu.in.
authors.forename: Nazir Ahmad
authors.initials: NA
authors.lastname: Dar
mesh_terms: D000368:Aged; D000428:Alcohol Drinking / Q000453:epidemiology; D001483:Base Sequence; D001628:Beverages; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D003252:Construction Materials; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D004032:Diet; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D005838:Genotype; D006798:Housing; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D012907:Smoking / Q000453:epidemiology; D012959:Socioeconomic Factors; D051760:Xeroderma Pigmentosum Group A Protein / Q000235:genetics* / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein; C086984:XPC protein, human
keywords: Esophageal squamous cell carcinoma risk; Gene-environment interaction; Kashmir; Polymorphism; Xeroderma pigmentosum A and C
references.citation: Chin J Cancer Res. 2012 Sep;24(3):181-9
references.pmid: 23359774
references.citation: Mol Biol Rep. 2012 Feb;39(2):1435-40
references.pmid: 21611749
references.citation: IARC Sci Publ. 1991;(105):210-3
references.pmid: 1855851
references.citation: Cancer Epidemiol Biomarkers Prev. 2002 Dec;11(12):1513-30
references.pmid: 12496039
references.citation: Rejuvenation Res. 2009 Jun;12(3):199-208
references.pmid: 19594328
references.citation: Int J Cancer. 2001 Jul 1;93(1):148-52
references.pmid: 11391635
references.citation: Br J Cancer. 2015 Jul 28;113(3):524-32
references.pmid: 26125444
references.citation: Mol Clin Oncol. 2015 May;3(3):649-654
references.pmid: 26137282
references.citation: Gene. 2014 May 25;542(1):64-8
references.pmid: 24582975
references.citation: Carcinogenesis. 2005 Jul;26(7):1263-71
references.pmid: 15746160
references.citation: Nat Rev Cancer. 2001 Oct;1(1):22-33
references.pmid: 11900249
references.citation: Br J Cancer. 2012 Oct 23;107(9):1618-23
references.pmid: 23033008
references.citation: Mol Biol Rep. 2012 Jan;39(1):527-34
references.pmid: 21559836
references.citation: Gene. 1999 Jul 8;234(2):187-208
references.pmid: 10395892
references.citation: Biochimie. 1999 Jan-Feb;81(1-2):15-25
references.pmid: 10214906
references.citation: Int J Cancer. 2005 Jun 20;115(3):478-83
references.pmid: 15700316
references.citation: Ai Zheng. 2006 Sep;25(9):1113-9
references.pmid: 16965652
references.citation: Pharmacogenomics J. 2016 Feb;16(1):41-6
references.pmid: 25823687
references.citation: Int J Hyg Environ Health. 2004 Sep;207(4):301-13
references.pmid: 15471094
references.citation: Cancer Res. 1988 Dec 1;48(23 ):6912-7
references.pmid: 3180100
references.citation: Cancer Epidemiol Biomarkers Prev. 1994 Jul-Aug;3(5):387-92
references.pmid: 7920205
references.citation: Carcinogenesis. 2009 May;30(5):785-92
references.pmid: 19270000
references.citation: Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2005 Aug;22(4):415-8
references.pmid: 16086280
references.citation: Mutat Res. 2007 Jun 1;619(1-2):68-80
references.pmid: 17363013
references.citation: Carcinogenesis. 2007 Mar;28(3):665-71
references.pmid: 17040931
references.citation: Carcinogenesis. 2001 Apr;22(4):593-7
references.pmid: 11285194
references.citation: Science. 1999 Dec 3;286(5446):1897-905
references.pmid: 10583946
references.citation: Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2662-6
references.pmid: 7708701
references.citation: Cancer Epidemiol Biomarkers Prev. 2006 Dec;15(12):2537-41
references.pmid: 17164382
references.citation: Biochimie. 1999 Jan-Feb;81(1-2):39-44
references.pmid: 10214908
references.citation: Cancer Res. 1980 Feb;40(2):298-302
references.pmid: 7356512
references.citation: PLoS One. 2014 Apr 15;9(4):e93937
references.pmid: 24736739
references.citation: Gut. 1992 Jan;33(1):11-5
references.pmid: 1740265
references.citation: Carcinogenesis. 2009 Mar;30(3):472-9
references.pmid: 19029193
references.citation: Clin Cancer Res. 2007 Jun 15;13(12):3753-8
references.pmid: 17575242
references.citation: Biochem J. 2002 Sep 15;366(Pt 3):767-75
references.pmid: 12059785
references.citation: Carcinogenesis. 2006 May;27(5):997-1007
references.pmid: 16308313
references.citation: Carcinogenesis. 2003 Mar;24(3):505-9
references.pmid: 12663511
references.citation: J Clin Gastroenterol. 2008 Sep;42(8):910-5
references.pmid: 18645534
references.citation: PLoS One. 2014 Oct 14;9(10):e109585
references.pmid: 25313490
references.citation: Lung Cancer. 2011 Aug;73(2):138-46
references.pmid: 21195504
references.citation: Mutat Res. 2007 Jul 28;631(2):101-10
references.pmid: 17531525
references.citation: PLoS One. 2012;7(9):e43412
references.pmid: 22984423
references.citation: Surgery. 2002 Jan;131(1 Suppl):S1-6
references.pmid: 11821780
references.citation: Cancer Epidemiol Biomarkers Prev. 2004 Dec;13(12):2242-6
references.pmid: 15598786
references.citation: Int J Cancer. 2015 Mar 15;136(6):E704-10
references.pmid: 25209106
references.citation: J Cancer Res Clin Oncol. 2008 Feb;134(2):263-70
references.pmid: 17653764
references.citation: Int J Cancer. 2013 Oct 15;133(8):1765-75
references.pmid: 23400628
references.citation: Int J Cancer. 2005 Jul 10;115(5):807-13
references.pmid: 15729698
references.citation: Diagn Pathol. 2014 May 23;9:96
references.pmid: 24886180
references.citation: Int J Cancer. 2005 Sep 20;116(5):768-73
references.pmid: 15849729
references.citation: Nat Genet. 2010 Sep;42(9):759-63
references.pmid: 20729853
references.citation: Carcinogenesis. 2004 May;25(5):757-63
references.pmid: 14729591
references.citation: Cancer Res. 2013 Jan 1;73(1):256-64
references.pmid: 23108145
references.citation: Lung Cancer. 2008 Feb;59(2):171-9
references.pmid: 17913280
references.citation: Mol Carcinog. 2010 Jun;49(6):611-8
references.pmid: 20232359
references.citation: Mol Cell. 1998 Aug;2(2):223-32
references.pmid: 9734359
references.citation: Mutagenesis. 2010 Nov;25(6):569-75
references.pmid: 20817763
references.citation: Chem Res Toxicol. 1998 Jun;11(6):559-603
references.pmid: 9625726
references.citation: Annu Rev Biochem. 2004;73:39-85
references.pmid: 15189136
references.citation: Mol Carcinog. 2003 Sep;38(1):1-13
references.pmid: 12949838
references.citation: Mutat Res. 2010 Dec 10;694(1-2):39-44
references.pmid: 20887739
references.citation: Cancer Lett. 1988 Feb;39(1):37-43
references.pmid: 3345506
references.citation: BMC Cancer. 2007 May 13;7:81
references.pmid: 17498315
references.citation: Mol Carcinog. 2011 Mar;50(3):189-98
references.pmid: 21104992
references.citation: Cancer Lett. 1988 Apr;39(3):259-65
references.pmid: 3359419
references.citation: Nat Rev Cancer. 2004 Nov;4(11):850-60
references.pmid: 15516958
references.citation: Science. 2001 Feb 16;291(5507):1284-9
references.pmid: 11181991
references.citation: Breast Cancer Res Treat. 2011 Aug;128(3):811-5
references.pmid: 21318603
references.citation: Int J Epidemiol. 1997 Dec;26(6):1159-65
references.pmid: 9447394
references.citation: Carcinogenesis. 2006 Mar;27(3):560-7
references.pmid: 16195237
references.citation: Mol Cell Biol. 2000 Nov;20(21):7980-90
references.pmid: 11027268
references.citation: Asian Pac J Cancer Prev. 2011;12(7):1867-72
references.pmid: 22126581
references.citation: World J Gastrointest Pathophysiol. 2014 Aug 15;5(3):335-43
references.pmid: 25133033
references.citation: Cancer Sci. 2013 Sep;104(9):1231-6
references.pmid: 23721087
references.citation: Eur J Hum Genet. 2008 Jun;16(6):724-34
references.pmid: 18285822
references.citation: Cancer Lett. 2008 Feb 18;260(1-2):48-55
references.pmid: 18037231
references.citation: Acta Oncol. 2008;47(3):379-84
references.pmid: 17882560
references.citation: Cancer Lett. 2005 May 10;222(1):67-74
references.pmid: 15837542
references.citation: Int J Cancer. 2006 Sep 1;119(5):1047-51
references.pmid: 16570268
references.citation: Int J Epidemiol. 2009 Aug;38(4):978-88
references.pmid: 19416955
references.citation: Lancet. 1998 Jan 3;351(9095):42
references.pmid: 9454056
references.citation: Am J Hum Genet. 2006 Mar;78(3):464-79
references.pmid: 16465622
references.citation: Environ Mol Mutagen. 2007 Oct;48(8):666-71
references.pmid: 17685459
references.citation: Oncol Rep. 2014 Aug;32(2):860-70
references.pmid: 24890309
references.citation: Mol Cell Biol. 2007 Oct;27(19):6606-14
references.pmid: 17682058
references.citation: Cancer Epidemiol Biomarkers Prev. 2002 Oct;11(10 Pt 1):993-7
references.pmid: 12376498
references.citation: Onco Targets Ther. 2015 Feb 05;8:385-94
references.pmid: 25709470
references.citation: Tumour Biol. 2014 Apr;35(4):3917-31
references.pmid: 24338715
references.citation: Oncogene. 2002 Dec 16;21(58):8949-56
references.pmid: 12483511
references.citation: Mol Biol Rep. 2012 Jun;39(6):6791-9
references.pmid: 22314912
references.citation: Annu Rev Genet. 1995;29:69-105
references.pmid: 8825469
references.citation: Carcinogenesis. 2004 Dec;25(12):2433-41
references.pmid: 15333465
references.citation: J Oral Pathol Med. 2006 Jan;35(1):11-8
references.pmid: 16393248
references.citation: J Hum Genet. 2008;53(1):18-33
references.pmid: 18097734
references.citation: Eur J Cancer. 2008 Oct;44(15):2241-53
references.pmid: 18771913
references.citation: Zhonghua Liu Xing Bing Xue Za Zhi. 2008 Sep;29(9):930-3
references.pmid: 19173862
references.citation: Mol Cell. 2001 Jul;8(1):213-24
references.pmid: 11511374
references.citation: Cancer Epidemiol Biomarkers Prev. 2007 Aug;16(8):1633-8
references.pmid: 17684138
references.citation: Invest Ophthalmol Vis Sci. 2014 Dec 09;55(12):8604-13
references.pmid: 25491297
references.citation: Chin Med J (Engl). 1985 Oct;98(10):749-52
references.pmid: 3938702
references.citation: Tumour Biol. 2014 May;35(5):4659-65
references.pmid: 24563277
references.citation: J Appl Genet. 2010;51(3):343-52
references.pmid: 20720310
references.citation: Carcinogenesis. 2000 Dec;21(12):2219-23
references.pmid: 11133811
references.citation: Nature. 2003 Dec 18;426(6968):789-96
references.pmid: 14685227
references.citation: Carcinogenesis. 2011 Dec;32(12):1855-61
references.pmid: 21926110
references.citation: Int J Cancer. 2009 Sep 15;125(6):1431-9
references.pmid: 19444904
references.citation: Nature. 2001 May 17;411(6835):366-74
references.pmid: 11357144
references.citation: Chin J Physiol. 2007 Dec 31;50(6):294-300
references.pmid: 18442012
references.citation: Environ Mol Mutagen. 2006 Dec;47(9):666-73
references.pmid: 17078101