A case-control study of the association of the polymorphisms and haplotypes of DNA ligase I with lung and upper-aerodigestive-tract cancers.
Tobacco smoking is a major risk factor for lung and upper-aerodigestive-tract (UADT) cancers. One possible mechanism for the associations may be through DNA damage pathways. DNA Ligase I (LIG1) is a DNA repair gene involved in both the nucleotide excision repair (NER) and the base excision repair (BER) pathways. We examined the association of 4 LIG1 polymorphisms with lung and UADT cancers, and their potential interactions with smoking in a population-based case-control study in Los Angeles County. We performed genotyping using the SNPlex method from Applied Biosystems. Logistic regression analyses of 551 lung cancer cases, 489 UADT cancer cases and 948 controls showed the expected associations of tobacco smoking with lung and UADT cancers and new associations between the LIG1 haplotypes and these cancers. For lung cancer, when compared to the most common haplotype (rs20581-rs20580-rs20579-rs439132 = T-C-C-A), the adjusted odds ratio (OR) is 1.2 (95% confidence limits (CL) = 0.95, 1.5) for the CACA haplotype, 1.4 (1.0, 1.9) for the CATA haplotype and 1.8 (1.1, 2.8) for the CCCG haplotype, after controlling for age, gender, race/ethnicity, education and tobacco smoking. We observed weaker associations between the LIG1 haplotypes and UADT cancers. Our findings suggest the LIG1 haplotypes may affect the risk of lung and UADT cancers.
Lee
Yuan-Chin Amy
YC
Department of Epidemiology, University of California at Los Angeles School of Public Health, Los Angeles, CA 90095-1772, USA.
Morgenstern
Hal
H
Greenland
Sander
S
Tashkin
Donald P
DP
Papp
Jeanette
J
Sinsheimer
Janet
J
Cao
Wei
W
Hashibe
Mia
M
You
Nai-Chieh Y
NC
Mao
Jenny T
JT
Cozen
Wendy
W
Mack
Thomas M
TM
Zhang
Zuo-Feng
ZF
D000328:Adult; D016022:Case-Control Studies; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006258:Head and Neck Neoplasms / Q000209:etiology / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*
C000607892:LIG1 protein, human; D011088:DNA Ligases; D000072481:DNA Ligase ATP