The 5p15.33 Locus Is Associated with Risk of Lung Adenocarcinoma in Never-Smoking Females in Asia
Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10−7 or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide association study of lung adenocarcinoma in never-smoking females (584 cases, 585 controls) among Han Chinese in Taiwan and found that the most significant association was for rs2736100 on chromosome 5p15.33 (p = 1.30×10−11). This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p = 5.38×10−11). A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p = 2.60×10−20, allelic risk = 1.54, 95% Confidence Interval (CI) 1.41–1.68). Risks for heterozygote and homozygote carriers of the minor allele were 1.62 (95% CI; 1.40–1.87), and 2.35 (95% CI: 1.95–2.83), respectively. In summary, our results show that genetic variation in the CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma.
Vyšlo v časopise:
The 5p15.33 Locus Is Associated with Risk of Lung Adenocarcinoma in Never-Smoking Females in Asia. PLoS Genet 6(8): e32767. doi:10.1371/journal.pgen.1001051
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1001051
Souhrn
Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10−7 or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide association study of lung adenocarcinoma in never-smoking females (584 cases, 585 controls) among Han Chinese in Taiwan and found that the most significant association was for rs2736100 on chromosome 5p15.33 (p = 1.30×10−11). This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p = 5.38×10−11). A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p = 2.60×10−20, allelic risk = 1.54, 95% Confidence Interval (CI) 1.41–1.68). Risks for heterozygote and homozygote carriers of the minor allele were 1.62 (95% CI; 1.40–1.87), and 2.35 (95% CI: 1.95–2.83), respectively. In summary, our results show that genetic variation in the CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma.
Zdroje
1. AmosCI
WuX
BroderickP
GorlovIP
GuJ
2008 Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nat Genet 40 616 622
2. HungRJ
McKayJD
GaborieauV
BoffettaP
HashibeM
2008 A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25. Nature 452 633 637
3. LiuP
VikisHG
WangD
LuY
WangY
2008 Familial aggregation of common sequence variants on 15q24–25.1 in lung cancer. J Natl Cancer Inst 100 1326 1330
4. McKayJD
HungRJ
GaborieauV
BoffettaP
ChabrierA
2008 Lung cancer susceptibility locus at 5p15.33. Nat Genet 40 1404 1406
5. RafnarT
SulemP
StaceySN
GellerF
GudmundssonJ
2009 Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat Genet 41 221 227
6. SpitzMR
AmosCI
DongQ
LinJ
WuX
2008 The CHRNA5-A3 region on chromosome 15q24–25.1 is a risk factor both for nicotine dependence and for lung cancer. J Natl Cancer Inst 100 1552 1556
7. WangY
BroderickP
WebbE
WuX
VijayakrishnanJ
2008 Common 5p15.33 and 6p21.33 variants influence lung cancer risk. Nat Genet 40 1407 1409
8. LandiMT
ChatterjeeN
YuK
GoldinLR
GoldsteinAM
2009 A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma. Am J Hum Genet 85 679 691
9. The Wellcome Trust Case Control Consortium 2007 Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447 661 678
10. DonnellyP
2008 Progress and challenges in genome-wide association studies in humans. Nature 456 728 731
11. ChanockSJ
HunterDJ
2008 Genomics: when the smoke clears. Nature 452 537 538
12. LamWK
2005 Lung cancer in Asian women-the environment and genes. Respirology 10 408 417
13. JouYS
LoYL
HsiaoCF
ChangGC
TsaiYH
2009 Association of an EGFR intron 1 SNP with never-smoking female lung adenocarcinoma patients. Lung Cancer 64 251 256
14. de BakkerPI
FerreiraMA
JiaX
NealeBM
RaychaudhuriS
2008 Practical aspects of imputation-driven meta-analysis of genome-wide association studies. Hum Mol Genet 17 R122 R128
15. ChanockSJ
ManolioT
BoehnkeM
BoerwinkleE
HunterDJ
2007 Replicating genotype-phenotype associations. Nature 447 655 660
16. WuC
HuZ
YuD
HuangL
JinG
2009 Genetic variants on chromosome 15q25 associated with lung cancer risk in Chinese populations. Cancer Res 69 5065 5072
17. BaiY
XuL
YangX
HuZ
YuanJ
2007 Sequence variations in DNA repair gene XPC is associated with lung cancer risk in a Chinese population: a case-control study. BMC Cancer 7 81
18. KimJH
KimH
LeeKY
ChoeKH
RyuJS
2006 Genetic polymorphisms of ataxia telangiectasia mutated affect lung cancer risk. Hum Mol Genet 15 1181 1186
19. JungHY
WhangYM
SungJS
ShinHD
ParkBL
2008 Association study of TP53 polymorphisms with lung cancer in a Korean population. J Hum Genet 53 508 514
20. ParkJY
ParkSH
ChoiJE
LeeSY
JeonHS
2002 Polymorphisms of the DNA repair gene xeroderma pigmentosum group A and risk of primary lung cancer. Cancer Epidemiol Biomarkers Prev 11 993 997
21. ZhangY
ShuXO
GaoYT
JiBT
YangG
2007 Family history of cancer and risk of lung cancer among nonsmoking Chinese women. Cancer Epidemiol Biomarkers Prev 16 2432 2435
22. ZhengW
ChowWH
YangG
JinF
RothmanN
2005 The Shanghai Women's Health Study: rationale, study design, and baseline characteristics. Am J Epidemiol 162 1123 1131
23. JinG
XuL
ShuY
TianT
LiangJ
2009 Common genetic variants on 5p15.33 contribute to risk of lung adenocarcinoma in a Chinese population. Carcinogenesis 30 987 990
24. TruongT
HungRJ
AmosCI
WuX
BickeböllerH
2010 Replication of lung cancer susceptibility loci at chromosomes 15q25, 5p15, and 6p21: a pooled analysis from the International Lung Cancer Consortium. J Natl Cancer Inst In press
25. TangL
LimW
EngP
LeongSS
LimTK
2010 Lung cancer in Chinese women: evidence for an interaction between tobacco smoking and exposure to inhalants in the indoor environment. Environ Health Perspect Environ Health Perspect In press
26. PetersenGM
AmundadottirL
FuchsCS
KraftP
Stolzenberg-SolomonRZ
2010 A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Nat Genet 42 224 228
27. SheteS
HoskingFJ
RobertsonLB
DobbinsSE
SansonM
2009 Genome-wide association study identifies five susceptibility loci for glioma. Nat Genet 41 899 904
28. YamaguchiH
CaladoRT
LyH
KajigayaS
BaerlocherGM
2005 Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia. N Engl J Med 352 1413 1424
29. CaladoRT
RegalJA
HillsM
YewdellWT
DalmazzoLF
2009 Constitutional hypomorphic telomerase mutations in patients with acute myeloid leukemia. Proc Natl Acad Sci U S A 106 1187 1192
30. MushirodaT
WattanapokayakitS
TakahashiA
NukiwaT
KudohS
2008 A genome-wide association study identifies an association of a common variant in TERT with susceptibility to idiopathic pulmonary fibrosis. J Med Genet 45 654 656
31. TsakiriKD
CronkhiteJT
KuanPJ
XingC
RaghuG
2007 Adult-onset pulmonary fibrosis caused by mutations in telomerase. Proc Natl Acad Sci U S A 104 7552 7557
32. ValdesAM
AndrewT
GardnerJP
KimuraM
OelsnerE
2005 Obesity, cigarette smoking, and telomere length in women. Lancet 366 662 664
33. WakeleeHA
ChangET
GomezSL
KeeganTH
FeskanichD
2007 Lung cancer incidence in never smokers. J Clin Oncol 25 472 478
34. LanQ
ChapmanRS
SchreinemachersDM
TianL
HeX
2002 Household stove improvement and risk of lung cancer in Xuanwei, China. J Natl Cancer Inst 94 826 835
35. ThorgeirssonTE
GellerF
SulemP
RafnarT
WisteA
2008 A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. Nature 452 638 642
36. PurcellS
NealeB
Todd-BrownK
ThomasL
FerreiraMA
2007 PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81 559 575
37. The International HapMap Consortium 2005 A haplotype map of the human genome. Nature 437 1299 1320
38. PriceAL
PattersonNJ
PlengeRM
WeinblattME
ShadickNA
2006 Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 38 904 909
39. MarchiniJ
HowieB
MyersS
McVeanG
DonnellyP
2007 A new multipoint method for genome-wide association studies by imputation of genotypes. Nat Genet 39 906 913
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Genetika Reprodukčná medicínaČlánok vyšiel v časopise
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