Methods And Marker Combinations For Screening For Predisposition To Lung Cancer

Abstract

The present invention relates to rapid, sensitive methods for determining whether a subject has or is at risk of developing lung cancer based on certain combinations of biomarkers, or biomarkers and biometric parameters. The methods consist of: a) quantifying in a test sample obtained from a subject, the amount of two or more biomarkers in a panel, the panel comprising at least one antibody and at least one antigen: b) comparing the amount of each biomarker quantified in the panel to a predetermined cutoff for said biomarker and assigning a score for each biomarker based on said comparison: c) combining the assigned score for each biomarker quantified in step b to obtain a total score for said subject: d) comparing the total score in step c with a predetermined total score and e) determining whether said subject has a risk of lung cancer based on the comparison in step d.

Description

RELATED APPLICATION INFORMATION[0001]This application claims priority to U.S. application Ser. No. 11 / 771,727, filed Jun. 29, 2007, which is a continuation-in-part of U.S. application Ser. No. 11 / 644,365 filed on Dec. 21, 2006, which claims priority to U.S. Patent Application No. 60 / 753,331 filed on Dec. 22, 2005, the contents of all are herein incorporated by reference.BACKGROUND OF THE INVENTION[0002]Lung cancer is the second most common cancer for both men and women in the United States, with an estimated 172,500 new cases projected to be diagnosed during 2005 (American Cancer Society statistics). It is the most common cause of cancer death for both sexes, with over 163,000 lung cancer related deaths expected in 2005. Lung cancer is also a major health problem in other areas of the world. In the European Union, approximately 135,000 new cases occur each year (Genesis Report, February 1995). Also, incidence is rapidly increasing in Central and Eastern Europe where men have the wor...

AI Technical Summary

Problems solved by technology

Lung cancer is also a major health problem in other areas of the world.

Early stage lung cancer can be detected by chest radiograph and the sputum cytological examination, however these procedures do not have sufficient accuracy to be routinely used as screening tests for asymptomatic individuals.

The potential technical problems that can limit the sensitivity of chest radiograph include suboptimal technique, insufficient exposure, and positioning and cooperation of the patient (See, T. G. Tape, et al., Ann. Intern. Med. 104: 663-670 (1986)).

False-negative interpretations are the cause of most errors and inconclusive results require follow-up testing for clarification (See, T. G. Tape et al., supra).

These statistics show that current procedures are failing to detect lung cancer at an early, treatable stage of the disease and that improved methods of detection and treatment are needed to reduce mortality.

Detecting recurrence by regular monitoring, however, does not greatly affect the mode of treatment and the overall survival time leading to the conclusion that current monitoring methods are not cost effective (See, K. S. Naunheim et al., Ann. Thorac. Surg. 60:1612-1616 (1995); G. L. Walsh et al., Ann. Thorac. Surg. 60: 1563-1572 (1995)).

However, even if implemented in clinical practice, the cost of CT screening would be high and the number of false positives leading to additional testing would also be high.

However, the lack of sensitivity that was characteristic of individual markers still prevents panels of tumor markers from being useful for early detection of lung cancer.

These markers have been found to be useful in staging, classifying, predicting outcomes for, and monitoring of lung cancer patients after their diagnosis has been made; however, these markers have not been found to be useful, either alone or in panels, for the early detection of the disease (See, S. Ando, et al., Anticancer Res. 21: 3085-3092 (2001); U.S. Preventive Services Task Force, Annals of Internal Medicine 140:738-739 (2004)).

The sensitivity of this technique, however, is limited by the degree of protein resolution of the two electrophoretic steps and by the detection step that depends on staining protein in gels.

Also, polypeptide instability will generate artifacts in the two-dimensional pattern.

However, these markers, kits and methods have not been adopted for use in routine practice as these markers and methods have not been duplicated in any laboratory.

To date none of these approaches have yielded novel autoantibodies useful for the early detection of lung cancer.

However, the number of cases and controls are limited (<200 total subjects) and the method needs to be validated on a much larger population.

Other environmental exposures such as asbestos, particulates, etc., can increase the risk of developing lung cancer as well.

Unfortunately, this algorithm is neither sensitive nor specific enough to be useful for the detection of early stage lung cancer.

Indeed, based on the cited algorithm, an individual with a significant smoking history will have a relative risk of 1 / 500 to 1 / 100 for developing lung cancer.

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