**4. Discussion**

A B **A B** 

versity of Chile, 2012

**Biomarkers**

**DR70**

**AQC**

**Figure 4.** AFB and WLB and Histopathology assay for a Mild Dysplasia Volunteer A101. Mild Dysplasia (B) Volunteer A109. Normal Epithelium Stain HE 100x. CeteCáncer. INNOVA CORFO. Thesis Avaria P. MSc, Faculty of Medicine, Uni‐

Fifty percent of the samples, classified as suspicious (12%) by AFB, were confirmed as metaplasia (33%) or dysplasia (17%) by histopathology. The rest of the samples classified by AFB as suspicious were classified by the histopathology as inflammation (25%) and hyper‐

> 27.3 (6.0 -61.0)

90.9 (58.7- 99.8)

The data shows that DR70 itself might contribute to confirm tumour diagnosis and to identify patients with advanced LC, with high sensitivity (95.8%) and specificity (91.9%) (Table 1). AQC

**LC PNL LC PNL**

91.9 (88.1-94.8)

89.4 (85.2-92.7)

**Specificity % (IC95%)**

> 91.9 (88.1-94.3)

> 89.4 (85.2-92.7)

plasia (25%). Non one was related with a normal histopathology sample (Figure 5).

**Sensitivity % (IC 95%)**

95.8 (784,9- 99,0)

64.0 (42.5- 82.0)

**Table 1.** Sensitivity and Specificity for DR70 and AQC, for LC and PNL

**AFB WLB** 

68 Oncogenesis, Inflammatory and Parasitic Tropical Diseases of the Lung

This is the first study in Latin America to complement image techniques with cellular and molecular biomarkers, to detect LC and PNL. These results provide scientific and clinical information for Chilean health authorities to include early detection of LC in the AUGE government programme, that provide additional health services for patients.

Our results presented here clearly demonstrate the reliability of both biomarkers to select good candidates for detect LC or pre neoplasic lesions (PNL). These results suggest that both AQC and DR70 might provide transcendentally information not only to confirm or suggest diag‐ nostic for LC, but also to surveillance screening of LC after treatment. It is as important to confirm diagnostic as predict a patient's response to certain cancer therapies or determine whether cancer has returned.

with glutathione and clearance of As, which may result in a higher risk of lung cancer or

One of the main conclusion is there is an interaction between CYP1A1 polymorphism, GSTM1 null genotype and LC risk, especially in people exposed to carcinogenic compounds like to As and PAHs. In conclusion, genetic biomarkers such as CYP1A1 and GSTM1 polymorphisms in addition to other genetic biomarkers and other biomarkers like to QAC and DR70 and clinical tools might provide relevant information to identify individuals at high risk to lung cancer as

This work was supported by Grants from INNOVA-CORFO Chile (07CN13PBT-48 and 11IDL2-10634, 2012). We also thank all the volunteers that accepted to participate in this project and to the permanent support of the Canada Embassy in Chile. The authors also thank Dr. Stephen Lam for his invaluable support, advise and helpful discussions. This work has been carried out with ethical committee approval of the Faculty of Medicine of University of Chile.

, P. Avaria1

[1] Adonis, M, Quinones, L, Gil, L, & Gibson, G. (1997). Hepatic enzyme induction and mutagenicity of airborne particulate matter from Santiago, Chile in the nourished

[2] Adonis, M, Martínez, V, Marín, P, Berrios, D, & Gil, L. (2005). Smoking habit and ge‐ netic factors associated with lung cancer in a population highly exposed to arsenic.

, J. Díaz1

, R. Miranda4

Relationship Between Toxicogenomic, Environment and Lung Cancer

http://dx.doi.org/10.5772/55663

71

, M. Campos2

,

respiratory tract illness.

**Acknowledgements**

**Author details**

, M. Chahuan2

2 San Borja Arriaran Hospital, Chile

3 Antofagasta Regional Hospital, Chile

4 Barros Lucos Trudeau Hospital, Chile

Toxicol Lett: , 159(1), 32-7.

and L. Gil1

, A. Zambrano3

1 CeTeCáncer, Faculty of Medicine, University of Chile, Chile

and malnourished rat. Xenobiotica: , 27(5), 527-36.

M. Adonis1

H. Benítez3

**References**

prevention and protection actions of public health.

These results obtained via biomarkers in blood and sputum were quite promising in elucidat‐ ing risk to LC, especially when the biomarkers studied are non invasive and inexpensive assays and could be an effective methods also to monitor the biological effects of environmental and occupational carcinogens.

Additionally, we presented evidences that showed that AFB is more sensitive than WLB to detect early lesions, thereby allowing their localisation for biopsy or interventional procedures. Then the association of WLB and AFB would increase the sensitivity to detect PNL.

Is well known that resolution of CT scan and other images technologies improves each year, allowing to detect more nodules, but not necessarily LC in early stages. Additionally, is well known the high frequency of lung nodules with undetermined significance and that LC often causes no symptoms until it is spread outside the lung. From this point of view, non invasive biomarkers and AFB might contribute as a first step in detecting pre- neoplastic a pre- invasive lesions. Screening in people with high LC risk including those with smoking habit and or nodules non necessary cancerous, might means a higher survival and improve the life quality. The screening in people with high risk of LC might be a good preventive way to improve the survival to 5 years, especially when different studies have shown an important association between genetic host characteristics and exposure to environmental carcinogens.

Genetic differences in metabolic activation and detoxification of environmental carcinogen, like PAHs and or As, may partially explain host susceptibility to chemically induced cancers (Daly et al., 1994; London et al, 2000, Kang et al, 2012).

Adonis et al (2005) showed the association of combined genotypes of cytochrome CYP1A1 (Msp1) and glutathione-S-transferase GSTM1 and lung cancer risk, for a population histori‐ cally exposed to As in the Antofagasta region. This study showed in the healthy group, a CYP1A1 \*2A allele frequency for MspI of 0.41, whereas for lung cancer group 0.46. No statically significant difference was observed between the healthy group and lung cancer group (*p* = 0.437, CI =−0.224 to 0.124). However, the CYP1A1 \*2A genotype was associated with an increased relative lung cancer risk O.R. = 2.08 (95% CI = 1.04–4.03, *p* = 0.04). In addition, 35% of healthy group and 39% of the lung cancer group were homozygote for the null variant allele of GSTM1. For men the CYP1A1 \*2A genotype was associated with a highly significant estimated relative lung cancer risk O.R. = 2.60 (95% CI = 1.07–5.94, *p* = 0.0334). The relative lung cancer risk for the total sample with the CYP1A1 \*2A/null GSTM1 genotype was 2.51 (O.R. = 2.51, CI = 1.07–5.40, *p* = 0.0322), which one increased when the sample was stratified by smoking habit (O.R. = 2.98, CI = 1.10–7.10, *p* = 0.0497) (Adonis et al, 2005).

These results suggest that patients with previous history of iAs exposure as the Antofagasta population, and with smoking habit might be have an additional factor related to genetic susceptibility to lung cancer. The cancer mortality rate in region II for iAs- associated cancers, as lung cancer, at least might be partly related to differences in As biotransformation. Indi‐ viduals with the CYP1A1\*2A and/or the combined CYP1A1\*2A and GSTM1 null genotype might have a greater capacity to metabolically active PAHs and lower capacity to conjugate with glutathione and clearance of As, which may result in a higher risk of lung cancer or respiratory tract illness.

One of the main conclusion is there is an interaction between CYP1A1 polymorphism, GSTM1 null genotype and LC risk, especially in people exposed to carcinogenic compounds like to As and PAHs. In conclusion, genetic biomarkers such as CYP1A1 and GSTM1 polymorphisms in addition to other genetic biomarkers and other biomarkers like to QAC and DR70 and clinical tools might provide relevant information to identify individuals at high risk to lung cancer as prevention and protection actions of public health.
