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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 medicína

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