http://www.ncbi.nlm.nih.gov/pubmed/22510351

Clin Cancer Res. 2012 Apr 17. [Epub ahead of print]

Defining a gene promoter methylation signature in sputum for lung cancer risk assessment.

Leng S, Do K, Yingling CM, Picchi MA, Wolf HJ, Kennedy TC, Feser WJ, Barón AE, Franklin WA, Brock MV, Herman JG, Baylin SB,Byers T, Stidley CA, Belinsky SA.

Source

Lung Cancer Program, Lovelace Respiratory Research Institute.

Abstract

PURPOSE:

To evaluate the methylation state of 31 genes in sputum as biomarkers in an expanded nested, case-control study from the Colorado Cohort and to assess the replication of results from the most promising genes in an independent case-control study of asymptomatic Stage I lung cancer patients from New Mexico.

EXPERIMENTAL DESIGN:

Cases and controls from Colorado and New Mexico were interrogated for methylation of up to 31 genes using nested, methylation specific PCR. Individual genes and methylation indices were used to assess the association between methylation and lung cancer with logistic regression modeling.

RESULTS:

Seventeen genes with odds ratios of 1.4 - 3.6 were identified and selected for replication in the New Mexico study. Overall, the direction of effects seen in New Mexico was similar to Colorado with the largest increase in case discrimination (odds ratios, 3.2 - 4.2) seen for the PAX5α, GATA5, and SULF2 genes. ROC curves generated from seven gene panels from Colorado and New Mexico studies showed prediction accuracy of 71% and 77%, respectively. A 22-fold increase in lung cancer risk was seen for a subset of New Mexico cases with five or more genes methylated. Sequence variants associated with lung cancer did not improve the accuracy of this gene methylation panel.

CONCLUSIONS:

These studies have identified and replicated a panel of methylated genes whose integration with other promising biomarkers could initially identify the highest risk smokers for computed tomography screening for early detection of lung cancer.