Serum concentrations of club cell secretory protein (Clara) and cancer mortality in adults: a population-based, prospective cohort study.
BACKGROUND
Club cell secretory protein (Clara) (CC16) is produced mainly by bronchiolar club cells and has been shown to have protective effects against airway inflammation and oxidative stress from cigarette smoking and related carcinogens. The goal of this study was to establish whether serum CC16 concentrations predict all-cause and cancer-specific mortality in adults.


METHODS
We used data from the population-based Tucson Epidemiological Study of Airway Obstructive Diseases (TESAOD), a prospective cohort study of respiratory health initiated in Tucson, AZ, USA, in 1972, that recruited a multistage stratified cluster sample of non-Hispanic white households. We measured serum CC16 concentrations in cryopreserved serum samples and reviewed vital status up to Jan 1, 2011, through contact with next of kin, collection of death certificates, and searches of the National Death Index. Our primary analysis was the relation of baseline serum CC16 to all-cause mortality or cause-specific mortality risk, analysed by adjusted Cox proportional hazards models.


RESULTS
1086 TESAOD participants aged 21-70 years at enrolment were eligible for inclusion. Of these, 653 (60%) had died by 2011, and cause of death was ascertained for 649 (99%). When adjusted for sex, age, education, body-mass index, smoking and pack-years, and baseline levels of lung function, serum CC16 concentrations at baseline were inversely associated with mortality risk over the study follow-up. Mortality risk increased for each 1-SD decrease in CC16 (adjusted hazard ratio [HR] 1·16 [95% CI 1·06-1·26]; p=0·0007). For cause-specific mortality, each 1-SD decrease in serum CC16 was associated with an increased risk of dying of cancer (adjusted HR 1·41 [1·19-1·67]; p<0·0001). In the subset of smokers, the corresponding adjusted HR for mortality by lung cancer was 1·52 (1·14-2·03; p=0·004).


CONCLUSIONS
Serum CC16 concentrations can predict mortality risk in the general adult population. The excess risk associated with lower CC16 concentrations is predominantly driven by cancer, particularly lung cancer.


BACKGROUND
National Heart, Lung, and Blood Institute.
Arizona Respiratory Center, University of Arizona, Tucson, AZ, USA; Centre for Research in Environmental Epidemiology (CREAL), CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain. Electronic address: stefano@email.arizona.edu.
Stefano
S
Guerra
Arizona Respiratory Center, University of Arizona, Tucson, AZ, USA; Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA.
Monica M
MM
Vasquez
Arizona Respiratory Center, University of Arizona, Tucson, AZ, USA.
Amber
A
Spangenberg
Arizona Respiratory Center, University of Arizona, Tucson, AZ, USA.
Marilyn
M
Halonen
Arizona Respiratory Center, University of Arizona, Tucson, AZ, USA.
Fernando D
FD
Martinez
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D002423:Cause of Death / Q000639:trends; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D005544:Forecasting; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance; D011446:Prospective Studies; D015996:Survival Rate / Q000639:trends; D013781:Texas / Q000453:epidemiology; D014598:Uteroglobin / Q000097:blood*; D055815:Young Adult
D014408:Biomarkers, Tumor; C556389:SCGB1A1 protein, human; D014598:Uteroglobin