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Original Research: LUNG CANCER |

Association Between Sputum Atypia and Lung Cancer Risk in an Occupational Cohort in Yunnan, China FREE TO VIEW

Ya-Guang Fan, MD; Ping Hu, SM, ScD; Yong Jiang, MPH; Run-Sheng Chang, MD; Shu-Xiang Yao, MD; Wendy Wang, PhD; Jie He, MD; Philip Prorok, PhD; You-Lin Qiao, MD, PhD
Author and Funding Information

*From the Department of Biology (Dr. Fan), Institute of Radiation Medicine, Chinese Academy of Medical Sciences, Tianjin, People's Republic of China; Department of Cancer Epidemiology (Drs. Jiang and Qiao), Cancer Institute, Chinese Academy of Medical Sciences, Beijing, People's Republic of China; Third People's Hospital of Honghe Autonomous District (Dr. Chang), Gejiu, Yunnan Province, People's Republic of China; Department of Epidemiology (Dr. Yao), Kunming Medical College, Kunming, Yunnan Province, People's Republic of China; Cancer Biomarkers Research Group (Dr. Wang), Division of Cancer Prevention, National Cancer Institute/National Institute of Health, Bethesda, MD; Cancer Institute (Dr. He), Chinese Academy of Medical Sciences, Beijing, People's Republic of China; and Biometry Research Group (Drs. Hu and Prorok), Divisions of Cancer Prevention, National Cancer Institute/National Institute of Health, Bethesda, MD.

Correspondence to: Ping Hu, SM, ScD, Mathematical Statistician, Biometry Research Group, Divisions of Cancer Prevention, National Cancer Institute/National Institute of Health, Executive Plaza North, Suite 3131, 6130 Executive Blvd, MSC 7354, Bethesda, MD 20892-7354; e-mail: ph107y@nih.gov


None of the authors have any financial interests in the subject matter or any actual or potential conflicts of interest.

This study was supported by the National Cancer Institute/National Institutes of Health, grant No. 263-MQ-511694. This article describes an ancillary study for the National Cancer Institute project “The Study of Early Markers of Lung Cancer Among Tin Miners in Yunnan China,” a federally funded registered clinical trial.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).


Chest. 2009;135(3):778-785. doi:10.1378/chest.08-1469
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Background:  Individuals with cytologic atypia in sputum may be at high risk for the development of lung cancer.

Methods:  A prospective cohort study was conducted among occupational tin miners in Yunnan China based on an annual lung cancer screening program. Sputum samples were collected prospectively at baseline and the following seven annual screenings. The associations between risk factors and sputum cytology were analyzed by univariate and multivariate logistic regression. A proportional hazard model was used to analyze the association between the baseline sputum results and the incidence of lung cancer. The effect of consecutive sputum cytology on the increase of lung cancer risk was analyzed by logistic regression.

Results:  Sputum cytologic atypia was associated with age, smoking, occupational radon and arsenic exposure, and asthma. Sputum cytologic atypia was an independent risk factor for lung cancer with an adjusted hazard ratio (HR) of 3.82 (95% confidence interval [CI], 2.82 to 5.18) in comparing normal to moderate or worse atypia. Compared to the lung cancer risk associated with normal sputum, the risk was significantly higher according to the degree of atypia for squamous carcinomas, small cell lung cancer and central lung cancer, with adjusted HRs of 5.70 (95% CI, 3.78 to 8.59), 3.32 (95% CI, 1.31 to 8.45), and 4.93 (95% CI, 3.51 to 6.92), respectively.

Conclusions:  Sputum atypia is associated with an increased risk of lung cancer. Sputum cytologic examination combined with other screening examinations may play an important role in the early detection of lung cancer or in the selection of the optimal target population for more intensive lung cancer screening among this occupational cohort or similar population.

Trial registration:  Clinicaltrials.gov Identifier: NCT00340405.

Lung cancer is the most common cancer worldwide. In 2005 it was estimated that there were > 490,000 new cases of lung cancer in China.1 Lung cancer is also a highly lethal disease; the 5-year survival rate for all stages combined is 15% in the United States.2,3 The reasons for the poor prognosis are late diagnosis and lack of effective treatment for symptomatic disease. In addition, the prognosis for lung cancer is related to the stage at which it is detected.4

Sputum cytologic examination as a lung cancer screening tool is not recommended by any organization for the general population or any high-risk population.5,6 The reason is that prior screening trials79 have not shown a reduction of lung cancer mortality. Although low-dose CT is considered the most potentially effective screening tool, it may be insensitive to superficial, preinvasive cancers in the central airways that may be manifested in sputum.10 Therefore, biomarkers that might be identifiable in the sputum may complement radiologic imaging for lung cancer. In addition, lung cancer risk has been demonstrated to increase with increasing levels of sputum cytologic dysplasia, particularly at levels of moderate atypia or worse.1115

The aim of this study was to investigate whether sputum atypia can be used as a predictor of increased lung cancer risk among participants in an occupational cohort in Yunnan, China. Although annual chest radiography was also conducted, we focus our analyses in this report on the results from sputum cytology examinations.

Study Design and Participants

The Yunnan Tin Corporation (YTC) study is a one-armed prospective cohort study initiated in 1992 with annual follow-up through 2001. Participants were tin miners in Yunnan, China and with at least 10 years of underground radon and/or arsenic exposure. Detailed inclusion criteria are presented elsewhere.16

At the time of enrollment, all participants completed standardized baseline questionnaires that included demographic characteristics; residential, occupational, smoking, and medical histories; and a dietary assessment component. From 1992 to 1999, a total of 9,295 eligible tin miners were enrolled in this study. Eight rounds of annual lung cancer screenings with chest radiography and sputum cytology were performed during this period. Among them, 9,084 participants underwent at least one sputum cytologic screening examination with adequate results. The YTC study received approval from the institutional review board, and informed consent was obtained for each participant.

Tobacco was consumed mainly in the form of cigarettes, water pipes, and Chinese long-stem pipes. The never-smoker was defined as having a smoking history of < 6 months. Screen-detected cancers were defined as those diagnosed within 12 months of a positive screen. All other cancers were classified as interval cancers. Detailed definitions of occupational radon and arsenic exposures are given elsewhere.17 In this study, occupational radon and arsenic exposure were grouped into four quartiles (Q1 to Q4) based on each individual's cumulative radon or arsenic levels, respectively.

Sputum Collection: Processing and Interpretation

Sputum samples were collected either spontaneously or by an induction procedure, and stored at room temperature in Saccomanno preservative. Specimens were smeared on glass slides and stained with Papanicolaou stain for routine cytologic examination. Slides were independently screened by two cytopathologists from the Labor Protection Institute in the YTC. Sputum cytologic screening results were classified into degrees as follows: (1) 1 = negative; (2) 2–1 = slight atypical metaplasia; (3) 2–2 = moderate atypical metaplasia; (4) 2–3 = grave atypical metaplasia; (5) 3 = suspicious for cancer; (6) 4 = highly suspicious for cancer; (7) 5–1 = epidermoid carcinoma; (8) 5–2 = adenocarcinoma; (9) 5–3 = undifferentiated carcinoma (includes both large cell and small cell); and (10) other cancer. The positive cytology slides were defined as the screening results of degrees 2–3 and above, and reread by a confirmatory reader. In this article, we focus on moderate atypical metaplasia (degree 2–2) or worse (degrees > 2–2) to investigate whether sputum atypical metaplasia can be used as a predictor of lung cancer.

Statistical Methods

The associations between risk factors and sputum cytology results were analyzed by univariate and multivariate logistic regression.18 Person-years of follow-up were calculated from the date of the first sputum cytologic screening to the date of lung cancer diagnosis or lung cancer death or censoring as of December 31, 2001. The proportional hazards model was used to analyze the association between baseline sputum results and lung cancer incidence. The effect of consecutive sputum cytology on the increase of lung cancer risk was also analyzed by logistic regression.18 The Kruskal-Wallis test was used to compare participant age, radon and arsenic exposures. The χ2 test of independence was used to evaluate the statistical significance of differences in proportions. All statistical tests were two-sided.

In this study, all analyses were restricted to the 9,084 participants who received at least one sputum cytology screening and had adequate results. Characteristics of the study participants are presented in Table 1. Most participants were men (93.9%), with women accounting for only 6.1% of participants. At the time of enrollment, 66.1% of participants were 40 to 59 years old. Of the participants, 23.9% never attended school, and 84.9% had a history of smoking. Table 1 also shows cumulative occupational arsenic and radon exposures and information on prior pulmonary diseases such as chronic bronchitis, asthma, and silicosis.

Table Graphic Jump Location
Table 1 Association Between Participant Characteristics and Sputum Cytology Among the YTC Cohort in Baseline Sputum Screening

*Worse than moderate atypia is included as “grave atypical metaplasia,” “suspicious for cancer,” “highly suspicious for cancer,” or “any types of carcinoma.”

†Adjusted for gender, age, education, smoking, occupational radon and arsenic exposure, and prior pulmonary diseases.

The association between personal/occupational characteristics and sputum cytology results in the baseline sputum screening is also given in Table 1. Moderate atypia or worse was found more often in men than women in univariate analysis (odds ratio [OR], 5.98; 95% confidence interval [CI], 1.48 to 24.16), but there was no significant association with gender in multivariate analysis. Risk of moderate or worse atypia was elevated with the increase of age level. There was an inverse relationship between education level and moderate atypia or worse, but it was not statistically significant. Compared with never-smokers, cigarette and water/stem pipe smokers had a significantly higher risk of moderate atypia or worse, according to univariate analysis. This significant result was not observed in the multivariate analysis. There was a positive relationship between moderate atypia or worse and radon exposure level. According to the multivariate analysis, participants with arsenic exposure levels in Q4, had a significantly higher risk of moderate atypia or worse than those with exposure levels in Q1; however, those with levels in Q2 to Q3 did not have a significantly greater risk than those in Q1. As to prior pulmonary diseases, only asthma was a risk factor of moderate atypia or worse.

By 2001, 502 lung cancer cases were confirmed. A total of 464 participants with lung cancer received at least one sputum cytologic screening and had valid diagnosis dates. Of these participants with lung cancer, 438 died by the end of 2001. The 38 participants whose diagnoses were confirmed only by cause of death, without a date of diagnosis, are not discussed further in this article. Results presented in Table 2 for lung cancer incidence ratios showed that gender, age, radon and arsenic exposure, smoking status, and prior pulmonary diseases were all potential risk factors for lung cancer. We observed an inverse relationship between education level and the risk of lung cancer. The lung cancer incidence ratio for cigarette and water/stem pipe smokers compared to never-smokers was 4.68 (95% CI, 3.06 to 7.14). As to occupational arsenic exposure, the incidence ratios from low to high (Q1 to Q4) were 1.00, 5.83 (95% CI, 3.52 to 9.66), 17.93 (95% CI, 12.13 to 26.49), and 8.88 (95% CI, 5.59 to 14.09), respectively. For radon exposure, the incidence ratios increased from 1.00 to 10.61 (95% CI, 7.63 to 14.75). Lung cancer risk was higher among men than women and among participants with prior chronic bronchitis or silicosis. The same pattern for all of the variables discussed above was also observed in the results of the mortality ratios (Table 2).

Table Graphic Jump Location
Table 2 Lung Cancer Incidence/Death Among the YTC Sputum Screening Cohort

*Lung cancer cases without date of diagnosis were not analyzed.

The association between sputum results and lung cancer incidence is displayed in Table 3. In the baseline sputum screening, moderate, worse than moderate atypia, or both were associated with a higher risk of lung cancer than was normal cytology. A total of 4,269 participants received the baseline (time 0 [T0]), and three subsequent annual (T1 to T3) sputum screenings. In the multivariate model, the odds ratio increased with the frequency of consecutive sputum screenings from 2.60 (95% CI, 1.41 to 4.79) for one baseline measurement (T0) to 4.62 (95% CI, 3.14 to 6.81) for four measurement (T0 to T3) [Table 3].

Table Graphic Jump Location
Table 3 Association Between Sputum Results and Lung Cancer Incidence Among the YTC Sputum Screening Cohort

*Adjusted for age, radon, arsenic, and smoking.

†Adjusted for age, radon, arsenic, smoking, gender, education, and prior pulmonary diseases.

The associations between occupational risk factors of lung cancer and baseline results of sputum cytology are shown in Table 4. Radon and arsenic exposures were highest among participants with moderate atypia or worse, followed by slight atypia, and finally normal sputum (p < 0.001). Participant age increased with the degree of atypical metaplasia from normal to moderate atypia or worse (p < 0.001). Smoking status and the degree of sputum atypia were related, with a higher proportion of normal sputum results among never-smokers than among cigarette and water/stem pipe smokers (94.3% vs 85.3%, respectively; p < 0.001). The reverse distribution was observed for moderate atypia or worse, which was significantly less common in never-smokers than in cigarette and water/stem pipe smokers (0.6% vs 2.6%, respectively; p < 0.001).

Table Graphic Jump Location
Table 4 Association Between Risk Factors of Lung Cancer and Sputum Results Among the YTC Cohort in Baseline Sputum Screening*

*Data are presented as No. (%) unless otherwise indicated.

The relationship between sputum atypia and lung cancer risk by histology and location is presented in Table 5. Compared to the lung cancer risk associated with normal sputum, the risk was significantly higher according to the degree of atypia for squamous carcinomas and small cell lung cancer (SCLC), with an adjusted hazard ratio (HR) of 5.70 (95% CI, 3.78 to 8.59) and 3.32 (95% CI, 1.31 to 8.45), respectively. Similarly, the adjusted HR for lung cancer with a central location was 4.93 (95% CI, 3.51 to 6.92). Of note, the degree of sputum cytology atypia was not related to the incidence of adenocarcinoma or other types of carcinoma.

Table Graphic Jump Location
Table 5 Association Between Sputum Results and Lung Cancer Risk Among the YTC Sputum Screening Cohort by Histology Type and Location

*Adjusted for age, radon, arsenic, and smoking. HR = hazard ratio.

†Adjusted for age, radon, arsenic, smoking, gender, education, and prior pulmonary diseases.

In this study, we mainly investigated the association between sputum atypia and lung cancer risk. Our results showed that age, asthma, and occupational radon and arsenic exposure were independent risk factors for sputum atypia (moderate atypia or worse). In addition, male gender, older age, less education, smoking, occupational radon and arsenic exposure, and prior pulmonary disease were all potential risk factors of lung cancer (incidence or death). These findings were similar to the earlier studies conducted in the YTC and elsewhere.1925 This study also indicated that sputum atypia increased the risk of lung cancer in both univariate and multivariate models.

There is little controversy that severe sputum atypia may lead to/or be associated with either invasive cancer or carcinoma in situ.2629 However, our study indicated that moderate atypia was also associated with an increased risk of lung cancer. The same association between moderate atypia and lung cancer risk was also observed in the Colorado study.12 Since all participants were exposed to radon and/or arsenic and most of them had a history of smoking or other risk factors for lung cancer, and all these risk factors were associated with an increase in moderate atypia, it was hard to distinguish moderate atypia as an independent risk factor of lung cancer from occupational exposure or just part of a multistep process in the development of lung cancer. However, after adjustment for other risk factors, there was still an increased risk for lung cancer from moderate atypia or worse, which showed that other risk factors might not account for the entire relationship between sputum atypia and lung cancer risk. Thus, sputum atypia is an independent risk factor for lung cancer, though it might be partly explained by the process of field cancerization in the respiratory epithelium.30

The YTC cohort had prominent occupational characteristics. First, all participants had serious radon and/or arsenic exposure, and second, squamous carcinomas and SCLC were the most common types of lung cancer among the YTC cohort. In our study, although sputum atypia might be an independent risk factor for lung cancer, age, smoking, occupational radon and arsenic exposure appear to be major confounding factors. In the Colorado study,12 there were very small changes in the HR for lung cancer associated with sputum atypia in the multivariate model as compared with of the HR changes in the univariate model. In our study, the crude HR was higher than the adjusted HR after age, smoking, and occupational radon and arsenic exposure were included. The adjusted HRs differed slightly depending on whether the adjustment included age, smoking, radon and arsenic exposure or included these variables plus gender, education, and prior pulmonary disease (Table 3). In addition, Table 4 shows that the distribution of smoking status and median age at baseline, and median occupational radon and arsenic exposure varied with the results of the baseline sputum cytologic examination (p < 0.001). Another implication of our study is that sputum atypia only increases the risk of squamous carcinoma and SCLC, ie, centrally located lung cancer. This may be because the central tumors arise from the larger bronchi, and adenocarcinomas are peripheral and arise from bronchioloalveolar epithelium. Centrally located cancers are likely induced by an inhaled carcinogen that is deposited in the central airway mucosa, thus implicating something in the workplace of these tin workers and not having the same effect on the periphery where adenocarcinomas are typically found.

Univariate analysis results showed that lack of education was a potential risk factor for lung cancer. This result might be confounded by occupational radon and arsenic levels. The tin miners with more education were more likely employed in a job with less occupational exposure and higher education.

Although sputum cytology is an insensitive screening tool,31 our results showed that increased lung cancer risk is associated with the frequency of consecutive annual sputum examinations. Similar results are also observed in other studies.32 This might imply that consecutive annual sputum examination increases the chance of detection of sputum atypia and thus, increases the chance of detection of lung cancer.

The strength of this study is the methodology. First, it involved a prospective cohort design. Personal and occupational characteristics and sputum samples were all obtained before the diagnosis of lung cancer. Second, both sputum cytology and chest radiographs were used as the screening tools for the consecutive annual lung cancer screenings. On one hand, this combination of screening tools was helpful in identifying all lung cancer cases during the study period and reducing the number of missed diagnoses. On the other hand, since the two screening examinations were performed on the same day but by two independent departments, it is unlikely that sputum cytology results were affected by chest radiography results or vice versa. In addition, our analysis showed that the level of chest radiograph compliance is very high and consistent in all the subgroups. A limitation of our study is that information about some risk factors was obtained by self-reporting. Both radon and arsenic exposure level were estimated based on work histories combined with general environmental monitoring, and monitoring data were for areas and not at the individual level.

In conclusion, our study of persons at high risk of lung cancer shows that moderate or worse sputum cytologic atypia predicts an increased risk of lung cancer. Sputum atypia might be helpful to identify high-risk individuals who could benefit from more intensive diagnostic examination and/or be enrolled into lung cancer chemoprevention trials. Further studies in different populations and using more sensitive molecular markers are warranted to investigate the relationship between sputum cytologic atypia and molecular markers in the sputum.

CI

confidence interval

HR

hazard ratio

OR

odds ratio

Q

quartile

SCLC

small cell lung cancer

T0 to 3

time 0 to 3

YTC

Yunnan Tin Corporation

We thank the staff of The Third People's Hospital of Honghe Prefecture, Gejiu City, Yunnan, China for their assistance in the collection of the follow-up data on the YTC screening cohort. We thank William Hocking, MD, Marshfield Clinic, and Paul Kvale, MD, Henry Ford Hospital, for their critical comments.

Yang L, Parkin DM, Ferlay DM, et al. Estimates of Cancer incidence in China for 2000 and projections for 2005. Cancer Epidemiol Biomarkers Prev. 2005;14:243-250. [PubMed] [CrossRef]
 
Brenner H. Long-term survival rates of cancer patients achieved by the end of the 20th century: a period analysis. Lancet. 2002;360:1131-1135. [PubMed]
 
Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA Cancer J Clin. 2006;56:106-130. [PubMed]
 
Mountain CF. The international system for staging lung cancer. Semin Surg Oncol. 2000;18:106-115. [PubMed]
 
Lung cancer screening: recommendation statement. Ann Intern Med. 2004;140:738-739. [PubMed]
 
Smith RA, Cokkinides V, Eyre HJ. American Cancer Society guidelines for the early detection of cancer, 2003. CA Cancer J Clin. 2003;53:27-43. [PubMed]
 
Fontana RS, Sanderson DR, Woolner LB, et al. Lung cancer screening: the Mayo program. J Occup Med. 1986;28:746-750. [PubMed]
 
Kubik AK, Parkin DM, Zatloukal P. Czech study on lung cancer screening: post-trial follow-up of lung cancer deaths up to year 15 since enrollment. Cancer. 2000;89:2363-2368. [PubMed]
 
Marcus PM, Bergstralh EJ, Fagerstrom RM, et al. Lung cancer mortality in the Mayo Lung Project: impact of extended follow-up. J Natl Cancer Inst. 2000;92:1308-1316. [PubMed]
 
McWilliams A, Mayo J, MacDonald S, et al. Lung cancer screening: a different paradigm. Am J Respir Crit Care Med. 2003;168:1167-1173. [PubMed]
 
Kennedy TC, Proudfoot SP, Franklin WA, et al. Cytopathological analysis of sputum in patients with airflow obstruction and significant smoking histories. Cancer Res. 1996;56:4673-4678. [PubMed]
 
Prindiville SA, Byers T, Hirsch FR, et al. Sputum cytological atypia as a predictor of incident lung cancer in a cohort of heavy smokers with airflow obstruction. Cancer Epidemiol Biomarkers Prev. 2003;12:987-993. [PubMed]
 
Risse EK, Vooijs GP, van't Hof MA. Diagnostic significance of “severe dysplasia” in sputum cytology. Acta Cytol. 1988;32:629-634. [PubMed]
 
Fontana RS, Sanderson DR, Taylor WF, et al. Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Mayo Clinic study. Am Rev Respir Dis. 1984;130:561-565. [PubMed]
 
Kennedy TC, Franklin WA, Prindiville SA, et al. High prevalence of endobronchial malignancy in high-risk patients with moderate dysplasia in sputum. Chest. 2004;125:109S. [PubMed]
 
Ratnasinghe D, Yao SX, Tangrea JA, et al. Polymorphisms of the DNA repair gene XRCC1 and lung cancer risk. Cancer Epidemiol Biomarkers Prev. 2001;10:119-123. [PubMed]
 
Qiao YL, Taylor PR, Yao SX, et al. Risk factors and early detection of lung cancer in a cohort of Chinese tin miners. Ann Epidemiol. 1997;7:533-541. [PubMed]
 
Hosmer DW, Lemeshow S. Applied logistic regression. Wiley series in probability and statistics. 1999; New York, NY John Wiley & Sons
 
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van Loon AJ, Goldbohm RA, van den Brandt PA. Lung cancer: is there an association with socioeconomic status in The Netherlands? J Epidemiol Community Health. 1995;49:65-69. [PubMed]
 
Mao Y, Hu J, Ugnat AM, et al. Socioeconomic status and lung cancer risk in Canada. Int J Epidemiol. 2001;30:809-817. [PubMed]
 
Saccomanno G, Archer VE, Auerbach O, et al. Development of carcinoma of the lung as reflected in exfoliated cells. Cancer. 1974;33:256-270. [PubMed]
 
Frost JK, Ball WC Jr, Levin ML, et al. Sputum cytopathology: use and potential in monitoring the workplace environment by screening for biological effects of exposure. J Occup Med. 1986;28:692-703. [PubMed]
 
Frost JK, Ball WC Jr, Levin ML, et al. Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Johns Hopkins study. Am Rev Respir Dis. 1984;130:549-554. [PubMed]
 
Tockman MS, Gupta PK, Myers JD, et al. Sensitive and specific monoclonal antibody recognition of human lung cancer antigen on preserved sputum cells: a new approach to early lung cancer detection. J Clin Oncol. 1988;6:1685-1693. [PubMed]
 
Hirsch FR, Franklin WA, Gazdar AF, et al. Early detection of lung cancer: clinical perspectives of recent advances in biology and radiology. Clin Cancer Res. 2001;7:5-22. [PubMed]
 
Frost JK, Fontana RS, Melamed MR, et al. Early lung cancer detection: summary and conclusions. Am Rev Respir Dis. 1984;130:565-570. [PubMed]
 
Thunnissen FB. Sputum examination for early detection of lung cancer. J Clin Pathol. 2003;56:805-810. [PubMed]
 

Figures

Tables

Table Graphic Jump Location
Table 1 Association Between Participant Characteristics and Sputum Cytology Among the YTC Cohort in Baseline Sputum Screening

*Worse than moderate atypia is included as “grave atypical metaplasia,” “suspicious for cancer,” “highly suspicious for cancer,” or “any types of carcinoma.”

†Adjusted for gender, age, education, smoking, occupational radon and arsenic exposure, and prior pulmonary diseases.

Table Graphic Jump Location
Table 2 Lung Cancer Incidence/Death Among the YTC Sputum Screening Cohort

*Lung cancer cases without date of diagnosis were not analyzed.

Table Graphic Jump Location
Table 3 Association Between Sputum Results and Lung Cancer Incidence Among the YTC Sputum Screening Cohort

*Adjusted for age, radon, arsenic, and smoking.

†Adjusted for age, radon, arsenic, smoking, gender, education, and prior pulmonary diseases.

Table Graphic Jump Location
Table 4 Association Between Risk Factors of Lung Cancer and Sputum Results Among the YTC Cohort in Baseline Sputum Screening*

*Data are presented as No. (%) unless otherwise indicated.

Table Graphic Jump Location
Table 5 Association Between Sputum Results and Lung Cancer Risk Among the YTC Sputum Screening Cohort by Histology Type and Location

*Adjusted for age, radon, arsenic, and smoking. HR = hazard ratio.

†Adjusted for age, radon, arsenic, smoking, gender, education, and prior pulmonary diseases.

References

Yang L, Parkin DM, Ferlay DM, et al. Estimates of Cancer incidence in China for 2000 and projections for 2005. Cancer Epidemiol Biomarkers Prev. 2005;14:243-250. [PubMed] [CrossRef]
 
Brenner H. Long-term survival rates of cancer patients achieved by the end of the 20th century: a period analysis. Lancet. 2002;360:1131-1135. [PubMed]
 
Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA Cancer J Clin. 2006;56:106-130. [PubMed]
 
Mountain CF. The international system for staging lung cancer. Semin Surg Oncol. 2000;18:106-115. [PubMed]
 
Lung cancer screening: recommendation statement. Ann Intern Med. 2004;140:738-739. [PubMed]
 
Smith RA, Cokkinides V, Eyre HJ. American Cancer Society guidelines for the early detection of cancer, 2003. CA Cancer J Clin. 2003;53:27-43. [PubMed]
 
Fontana RS, Sanderson DR, Woolner LB, et al. Lung cancer screening: the Mayo program. J Occup Med. 1986;28:746-750. [PubMed]
 
Kubik AK, Parkin DM, Zatloukal P. Czech study on lung cancer screening: post-trial follow-up of lung cancer deaths up to year 15 since enrollment. Cancer. 2000;89:2363-2368. [PubMed]
 
Marcus PM, Bergstralh EJ, Fagerstrom RM, et al. Lung cancer mortality in the Mayo Lung Project: impact of extended follow-up. J Natl Cancer Inst. 2000;92:1308-1316. [PubMed]
 
McWilliams A, Mayo J, MacDonald S, et al. Lung cancer screening: a different paradigm. Am J Respir Crit Care Med. 2003;168:1167-1173. [PubMed]
 
Kennedy TC, Proudfoot SP, Franklin WA, et al. Cytopathological analysis of sputum in patients with airflow obstruction and significant smoking histories. Cancer Res. 1996;56:4673-4678. [PubMed]
 
Prindiville SA, Byers T, Hirsch FR, et al. Sputum cytological atypia as a predictor of incident lung cancer in a cohort of heavy smokers with airflow obstruction. Cancer Epidemiol Biomarkers Prev. 2003;12:987-993. [PubMed]
 
Risse EK, Vooijs GP, van't Hof MA. Diagnostic significance of “severe dysplasia” in sputum cytology. Acta Cytol. 1988;32:629-634. [PubMed]
 
Fontana RS, Sanderson DR, Taylor WF, et al. Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Mayo Clinic study. Am Rev Respir Dis. 1984;130:561-565. [PubMed]
 
Kennedy TC, Franklin WA, Prindiville SA, et al. High prevalence of endobronchial malignancy in high-risk patients with moderate dysplasia in sputum. Chest. 2004;125:109S. [PubMed]
 
Ratnasinghe D, Yao SX, Tangrea JA, et al. Polymorphisms of the DNA repair gene XRCC1 and lung cancer risk. Cancer Epidemiol Biomarkers Prev. 2001;10:119-123. [PubMed]
 
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