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Lung cancer gene associated with COPD: triple whammy or possible confounding effect?

R. P. Young, R. J. Hopkins, B. A. Hay, M. J. Epton, P. N. Black, G. D. Gamble
European Respiratory Journal 2008 32: 1158-1164; DOI: 10.1183/09031936.00093908
R. P. Young
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R. J. Hopkins
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B. A. Hay
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M. J. Epton
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P. N. Black
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G. D. Gamble
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Tables

  • Table 1—

    Primer sequences for iPLEX™ genotyping assay for the nicotinic acetylcholine receptor α5 and α3 subunit single nucleotide polymorphism (SNP)

    SNP IDFirst PCR primerSecond PCR primerExtension primer
    rs16969968ACGTTGGATGCACGGACGTTGGATGTCTAGAAACATTGGAAGCTGCGCTC
    ACATCATTTTCCTTCCACATTGGAAGC
    rs1051730ACGTTGGATGCAGCAACGTTGGATGTCAAGGACTCATCAAAGCCCCAGGCTA
    GTTGTACTTGATGTCTATTGGGAGAGC
    • iPLEX™ is manufactured by Sequenom, San Diego, CA, USA.

  • Table 2—

    Study characteristics

    ParameterLung cancerCOPDControl smokers
    Subjects n454458488
    Males535960
    Age yrs69±1066±965±10
    Smoking history
     Current smoker354048
     Age started smoking yrs18±417±317±3
     Length of time smoked yrs41±1242±1135±11
     Pack-yrs41±25*47±20*40±19*
     Cigarettes·day−120±1023±924±11
     Time since quitting yrs11.4±6.79.8±7.413.9±8.1
    History of other exposures
     Work dust63*59*47*
     Work fume414038
     Asbestos23*22*16*
    Family history
     COPD333728
     Lung cancer19*11*9*
    Lung function
     FEV1 L1.86±0.48*1.25±0.48*2.86±0.68*
     FEV1 % pred73*46*99*
     FEV1/FVC64±13*46±8*78±7*
     Spirometric COPD#57*100*0*
    • Data are presented as % or mean±sd, unless otherwise stated. COPD: chronic obstructive pulmonary disease; FEV1: forced expiratory volume in one second; % pred: % predicted; FVC: forced vital capacity. #: according to Global Initiative for Chronic Obstructive Lung Disease stage 2. *: p<0.05.

  • Table 3—

    Genotype frequencies for the nicotinic acetylcholine receptorα5 subunit single nucleotide polymorphism (rs16969968) in chronic obstructive pulmonary disease (COPD) and lung cancer (LC) cohorts compared with smoking controls

    Subjects nCall rateGGGAAAOR (95% CI)#p-value#
    Primary cohorts
     Controls47597225 (47)205 (43)45 (9)
     COPD44597166 (37)219 (49)60 (14)1.5 (1.0–2.3)#0.06
     LC43796170 (39)199 (46)68 (16)1.8 (1.2–2.7)0.005
    Subgroup analyses
     COPD and LC+COPD706252 (36)344 (49)110 (16)1.8 (1.2–2.6)0.002
     LC+COPD¶26186 (33)125 (48)50 (19)2.3 (1.4–3.6)0.0002
     LC only16881 (48)69 (41)18 (11)1.2 (0.6–2.1.)0.64
    • Data are presented as % or n (%), unless otherwise stated. OR: odds ratio; 95% CI: 95% confidence interval. #: AA versus GA/GG compared with matched smoking controls (Mantel–Haenszel); ¶: AA versus GA/GG compared with COPD and lung cancer alone (OR 2.0, 95% CI 1.1–3.7; p = 0.02).

  • Table 4—

    Genotype frequencies for the nicotinic acetylcholine receptorα5 subunit single nucleotide polymorphism (rs16969968) across all cohorts stratified by chronic obstructive pulmonary disease (COPD) and lung cancer (LC)

    Subjects nGGGAAAOR (95% CI)#p-value#
    Cohorts stratified by COPD
     No COPD643306 (48)274 (43)63 (10)
     COPD706252 (36)344 (49)110 (16)1.7 (1.2–2.4)0.002
    Cohorts stratified by LC
     No LC¶920391 (43)424 (46)105 (11)
     LC+437170 (39)199 (46)68 (16)1.4 (1.0–2.0)0.03
    • Data are presented as n (%), unless otherwise stated. OR: odds ratio; 95% CI: 95% confidence interval. #: AA versus GA/GG (Mantel–Haenszel); ¶: 48% with no LC have COPD; +: 60% with LC have COPD.

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Lung cancer gene associated with COPD: triple whammy or possible confounding effect?
R. P. Young, R. J. Hopkins, B. A. Hay, M. J. Epton, P. N. Black, G. D. Gamble
European Respiratory Journal Nov 2008, 32 (5) 1158-1164; DOI: 10.1183/09031936.00093908

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Lung cancer gene associated with COPD: triple whammy or possible confounding effect?
R. P. Young, R. J. Hopkins, B. A. Hay, M. J. Epton, P. N. Black, G. D. Gamble
European Respiratory Journal Nov 2008, 32 (5) 1158-1164; DOI: 10.1183/09031936.00093908
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