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M. Adonis



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    P3.02 - Poster Session 3 - Novel Cancer Genes and Pathways (ID 149)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P3.02-015 - Genomic Alteration in sputum samples and DNAfc of Lung Cancer high risk Chilean Population. (ID 2614)

      09:30 - 09:30  |  Author(s): M. Adonis

      • Abstract

      Background
      Background: Antofagasta region in northern Chile shows the highest lung cancer (LC) mortality rate in the country. This population was exposed to arsenic (As) in drinking water of concentrations as high as 870 mg/L. Between 2003 and 2007, Antofagasta region showed a mortality rate of 30.8/100,000. It has been suggested that variation in As susceptibility among individuals might be partly due to differences in As biotransformation in addition to other genomic factors associated to the carcinogenic process. Objective: To determine the association of genomic variations (SNPs, and DNA copy-number alterations (CNAs) and susceptibility to LC, in blood and induced sputum samples collected from a LC risk sample population.

      Methods
      Materials and Methods: The 400 high-risk volunteers from Antofagasta and Metropolitan region was split in 2 groups, controls and cases, according to the result of early detection assays including automatic quantitative cytometry (AQC), DR70 and autofluorescence bronchoscopy (AFB). Copy number variants (CNVs) and single nucleotide polymorphisms (SNPs) were determined in genomic DNA of peripheral blood using TaqMan QPCR assays. Odd ratios (OR) were estimated by conditional likelihood and significance as exact mid-p values. Whole genome CGH profiles were generated with HEEBO 70-mer oligonucleotide microarrays.

      Results
      Results: Among 8 polymorphisms assayed (5 SNPs and 3 CNVs), CYP1A1 SNP rs1048943 was associated both to pre-neoplastic lesions (PNL) and cancer histopathology (OR 2.66, p=0.02). The CYP1B1 SNP rs1056836 was associated to LC, although no significantly. Some differences in the AS3MT SNP rs11191439 were observed between individuals from Antofagasta and Santiago. Additionally, the genomic profiles of sputum DNA and circulating cell-free DNA (cfDNA) from serum samples showed discrete differences among LC cases, pre-neoplastic lesions (PNL) and healthy controls. Chromosome 7p arm showed a significant gain in sputum DNA from cancer patients.

      Conclusion
      Conclusions: Conclusions: Our results suggest that SNPs associated to CYP450, like to CYP1A1 and 1B1, might be related to LC etiology. Additionally, genomic profiles from sputum DNA and cfDNA might be useful to detect PNL as complementary tools. Finally, this panel of genomic biomarkers in addition to DR70, AQC and AFB could be helpful to identify individuals susceptible to develop LC, and as complementary tools for LC early detection. These findings might be relevant in prevention and early detection of LC. Supported by INNOVA CORFO Chile: Grants 07CN13B48 and 11IDL2-10634.