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

doi:10.1183/09031936.00093908

Tables

Table 1—

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

SNP ID	First PCR primer	Second PCR primer	Extension primer
rs16969968	ACGTTGGATGCACGG	ACGTTGGATGTCTAGAAA	CATTGGAAGCTGCGCTC
	ACATCATTTTCCTTC	CACATTGGAAGC
rs1051730	ACGTTGGATGCAGCA	ACGTTGGATGTCAAGGAC	TCATCAAAGCCCCAGGCTA
	GTTGTACTTGATGTC	TATTGGGAGAGC

iPLEX™ is manufactured by Sequenom, San Diego, CA, USA.

Table 2—

Study characteristics

Parameter	Lung cancer	COPD	Control smokers
Subjects n	454	458	488
Males	53	59	60
Age yrs	69±10	66±9	65±10
Smoking history
Current smoker	35	40	48
Age started smoking yrs	18±4	17±3	17±3
Length of time smoked yrs	41±12	42±11	35±11
Pack-yrs	41±25*	47±20*	40±19*
Cigarettes·day⁻¹	20±10	23±9	24±11
Time since quitting yrs	11.4±6.7	9.8±7.4	13.9±8.1
History of other exposures
Work dust	63*	59*	47*
Work fume	41	40	38
Asbestos	23*	22*	16*
Family history
COPD	33	37	28
Lung cancer	19*	11*	9*
Lung function
FEV₁ L	1.86±0.48*	1.25±0.48*	2.86±0.68*
FEV₁ % pred	73*	46*	99*
FEV₁/FVC	64±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 n	Call rate	GG	GA	AA	OR (95% CI)^#	p-value^#
Primary cohorts
Controls	475	97	225 (47)	205 (43)	45 (9)
COPD	445	97	166 (37)	219 (49)	60 (14)	1.5 (1.0–2.3)^#	0.06
LC	437	96	170 (39)	199 (46)	68 (16)	1.8 (1.2–2.7)	0.005
Subgroup analyses
COPD and LC+COPD	706		252 (36)	344 (49)	110 (16)	1.8 (1.2–2.6)	0.002
LC+COPD^¶	261		86 (33)	125 (48)	50 (19)	2.3 (1.4–3.6)	0.0002
LC only	168		81 (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 n	GG	GA	AA	OR (95% CI)^#	p-value^#
Cohorts stratified by COPD
No COPD	643	306 (48)	274 (43)	63 (10)
COPD	706	252 (36)	344 (49)	110 (16)	1.7 (1.2–2.4)	0.002
Cohorts stratified by LC
No LC^¶	920	391 (43)	424 (46)	105 (11)
LC⁺	437	170 (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.