原创力文档different effects of tert, tp63, and cyp2a6 polymorphism on individual risk of tobacco-related lung cancer in male japanese smokers叔的不同影响,tp63,体内cyp2a6基因表现多态性对个人与烟草相关的日本男性吸烟者患肺癌的风险.pdfVIP
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different effects of tert, tp63, and cyp2a6 polymorphism on individual risk of tobacco-related lung cancer in male japanese smokers叔的不同影响,tp63,体内cyp2a6基因表现多态性对个人与烟草相关的日本男性吸烟者患肺癌的风险
Journal of Cancer Therapy, 2011, 2, 690-696
doi:10.4236/jct.2011.25093 Published Online December 2011 (http://www.SciRP.org/journal/jct)
Different Effects of TERT, TP63, and CYP2A 6
Polymorphism on Individual Risk of
Tobacco-Related Lung Cancer in Male
Japanese Smokers
1* 2,3* 4 1,2 1#
Makiko Shimizu , Kazuma Kiyotani , Hideo Kunitoh , Tetsuya Kamataki , Hiroshi Yamazaki
1Showa Pharmaceutical University, Tokyo, Japan; 2Hokkaido University, Sapporo, Japan; 3RIKEN Center for Genomic Medicine,
Yokohama, Japan; 4Mitsui Memorial Hospital, Tokyo, Japan.
E-mail: #hyamazak@ac.shoyaku.ac.jp
Received August 26th, 2011; revised September 27th, 2011; accepted October 6th, 2011.
ABSTRACT
Recent genome-wide association studies have identified lung cancer susceptibility loci, such as chromosome 5p 15 (te-
lomerase reverse transcriptase, TERT and cleft lip and palate transmembrane protein 1-like, CLPTM1L), 15q25 (nico-
tinic cholinergic receptor α, CHRNA3-CHRNA5), and 3q28 (tumor protein p63, TP63). Replication study was per-
formed to confirm the association of the recently-identified susceptible loci (i.e., TERT-CLPTM1L, CHRNA3-CHRNA5,
and TP63) in a total of 1460 male Japanese smokers (885 lung cancer cases and 575 healthy control subjects), which
were previously studied for a low odds ratio of impaired or deletion polymorphism in cytochrome P450 2A 6 (CYP2A 6)
for lung cancer risk . The minor allele frequency (0.442) of rs2736100 on 5p 15 (TERT) was significantly higher in lung
cancer cases than that (0.395) of controls, with an odds ratio of 1.27 (95% CI of 1.07 - 1.50, p = 0.00504). A series of
subgroup analyses revealed the significant associations of rs4488809 (TP63, odds ratio of 1.21, p = 0.0422) and
rs2736100 (TERT, odds ratio
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