Chlamydia pneumoniae and Lung Cancer: Epidemiologic Evidence

Alyson J. Littman; Lisa A. Jackson; Thomas L. Vaughan

doi:10.1158/1055-9965.EPI-04-0599

DOI: 10.1158/1055-9965.EPI-04-0599 Published April 2005

Article Figures & Data

Tables

Table 1.

Summary of nested case-control studies of C. pneumoniae and lung cancer risk with blood collected before lung cancer diagnosis in cases and a comparable time in controls

First author, year, location	Population	Number of subjects	Time between blood sampling and lung cancer diagnosis/censoring (y)	Variables adjusted for in multivariate models
Laurila, 1997 (23), Finland	Male smokers involved in a randomized trial of β-carotene and α-tocopherol	230 cases/230 controls	3-8 (median = 6.1)	Years of smoking and cigarettes smoked per day
Anttila, 2003 (28), Finland	Women in 1st trimester of pregnancy in Finnish Maternity Cohort	58 cases/287 controls	1.6-16.7 (mean = 9.1)	Current smoking defined by serum cotinine levels
Littman, 2004 (29), USA	Men and women involved in a randomized trial of β-carotene and retinol	508 cases/508 controls	0-16 (median = 9)	Years of smoking, cigarettes smoked per day, education, and body mass index (kg/m²)

Table 2.

Summary of case-control studies of C. pneumoniae and lung cancer risk with blood sampled at or after lung cancer diagnosis and at a comparable time in the controls

First author, year, location	Number of cases/controls	Case population/selection	Control population/selection	Matching factors	Confounders adjusted for
Jackson, 2000 (26), USA	148 cases/148 controls	Men in WA state diagnosed with LC between 5/93 and 7/96, identified through the SEER cancer registry. Population based.	Men without LC identified through random digit dialing.	Age (5-y categories) and gender	Smoking status (current or former), pack-years (<40 or ≥40) and education
Koyi, 2001 (25), Sweden	177 cases/C1 = 68, C2 = 111	Diagnosed with LC at a single hospital between 2/97 and 2/98. Hospital based.	C1: Consecutive blood donors who were former or current smokers presenting at the same hospital during spring 1998 (exclusions: history of MI, medication for hypertension, or other CV diseases). C2: Participants in a study of current and ex-smokers >70 y old	None	None
Kocazeybek, 2003 (27), Turkey	123 cases/123 controls	Smokers admitted to an Istanbul hospital with a diagnosis of LC between 6/98 and 7/2000. Hospital based.	Healthy hospital staff, relatives of the patients, blood donors, or persons with similar age, sex, and smoking habits and not having any medical treatment for a local or systemic disease and not admitted to the hospital in the previous 2 months	Age (5-y age group), sex, living environment (i.e., province), smoking status (former or current), duration (10-y categories), and quantity of cigarettes smoked (4 categories)	In primary analyses, none.

Abbreviations: WA, Washington; LC, lung cancer; MI, myocardial infarction; CV, cardiovascular; SEER, Surveillance, Epidemiology, and End Results; C1, control group 1; C2, control group 2.

Table 3.

Selected results from studies on C. pneumoniae infection and lung cancer risk

First author, year, location	Definition of chronic infection	Overall results	Findings by age at diagnosis/reference	Other subgroup findings	Comments
Laurila, 1997 (23), Finland	“Strong or moderate” evidence*	1.6 (1.0-2.3)	50-59 y: OR, 2.9; 95% CI, 1.5-5.4	Squamous or small cell cancer: OR, 1.7; 95% CI, 1.0-2.8
						≥60 y: OR, 0.9; 95% CI, 0.5-1.6	Follow-up
							<5 y: OR, 2.0; 95% CI, 1.1-3.6
							≥5 y: OR, 1.2; 95% CI, 0.5-2.5
Jackson, 2000 (26), USA	IgA ≥ 16	1.4 (0.9-2.3)^†	<60 y: OR, 2.7; 95% CI, 1.2-5.9	Association stronger among current smokers <60 y at diagnosis than former smokers:	Blood specimens were obtained from only 47% of cases who completed interviews in counties where blood was collected, mainly because of death or illness.
						≥ 60 y: OR, 0.7; 95% CI, 0.3-1.4	Current: OR, 4.6; 95% CI, 1.4-13.7
							Former: OR, 1.5; 95% CI, 0.5-4.8
Koyi, 2001 (25), Sweden	IgA ≥ 64^‡			ORs were stronger among men than women (except for IgA ≥ 64 with cases compared with C2).	Possible confounding by age, which differed between the case and control groups
		Cases vs. C1		9.9 (4.6-22.2)^†		For IgG ≥ 512:
		Cases vs. C2		5.0 (3.2-7.9)^†		C1: Men: OR, 10.2; 95% CI, 4.0-27.9
		IgG ≥ 512^‡				C1: Women: OR, 1.7; 95% CI, 0.5-7.0
		Cases vs. C1		4.2 (2.1-8.9)^†		C2: Men: OR, 3.6; 95% CI, 2.0-6.7
		Cases vs. C2		2.5 (1.6-4.0)^†		C2: Women: OR, 1.3; 95% CI, 0.6-2.6
Kocazeybek, 2003 (27), Turkey	IgG ≥ 512 and IgA ≥ 40^§	4.6 (2.3-10.2)^†	Men < 55 y: OR, 18.0; 95% CI, 4.6-154	Men: OR, 5.3; 95% CI, 2.4-12.9	Possible selection bias; possible exposure misclassification due to use of higher value in cases only
Kocazeybek, 2003 (27), Turkey	IgG ≥ 512 and IgA ≥ 40^§	4.6 (2.3-10.2)^†				Men ≥ 55 y: OR, 1.0; 95% CI, 0.3-3.3	Women: OR, 2.0; 95% CI, 0.3-22.1
Anttila, 2003 (28), Finland	IgA ≥ 16	1.6 (0.9-2.8)		ORs for IgG antibody titers (≥32 and ≥128) and IC (≥2 and ≥4) were of similar magnitude (1.7 to 2.2)	Mean age of cases at diagnosis was 41 y (range 22-53 y)
Anttila, 2003 (28), Finland		IgA ≥ 64	2.1 (1.2-3.9)		Mean age of cases at diagnosis was 41 y (range 22-53 y)
Littman, 2004 (29), USA	IgA ≥ 16	1.2 (0.9-1.6)		Male asbestos-exposed workers: OR, 1.9; 95% CI, 0.9-3.7; former smokers: OR, 2.1; 95% CI, 1.1-4.1; squamous cell carcinoma: OR, 1.7; 95% CI, 1.1-2.8

Abbreviations: IC, immune complexes; OR, odds ratio; CI, confidence interval; CI, control group #1 (see Table 2); C2,control group #2 (see Table 2).
↵* Blood sampled at baseline and at 3-y follow-up used to assess exposure. Strong evidence defined as IgA antibodies ≥16 and IC ≥ 4 in both samples, moderate evidence defined as IgA ≥ 16 in both samples or IC ≥ 4 in both samples and IgA ≥ 16 in second sample.
↵† Calculated from data presented in published articles.
↵‡ Final titer defined as higher value of blood sampled at diagnosis (all) or 3 months later (n = 127).
↵§ Final titer defined as higher value of blood sampled at diagnosis or 1 month later.