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Genetic Susceptibility to Lung Cancer Based on Candidate Genes in a Sample from the Mexican Mestizo Population: A Case–Control Study

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Abstract

Background

Lung cancer (LC) is the leading cause of mortality caused by neoplasias worldwide. Although cigarette smoking is the primary cause, not all smokers develop LC. Polymorphic variations in genes associated with carcinogen metabolism, DNA repair, and cell-cycle dysregulation may alter an individual risk of developing LC. A polygenic cancer model was proposed, which considers genetic susceptibility to cancer is a global mechanism and suggests that it might be defined by the contributions of low-risk alleles in several candidate genes. This study focused on the analysis of 15 polymorphisms in 12 low-penetrance genes in a case–control study of a sample of Mexican Mestizo population.

Methods

A case–control study was performed with a total of 572 unrelated individuals, including 190 cases with a primary LC diagnosis and 382 healthy controls. The polymorphic status of the individuals was determined by TaqMan probe and RFLP techniques. The association between LC and genotype score (GS) was assessed by logistic regression.

Results

The results suggests a protective effect of the genotypes Arg/Lys of AhR rs2066853 (odds ratio [OR] 0.55, p = 0.03), Ile/Val of CYP1A1 rs1048943 (OR 0.49, p = 0.009), Tyr/His of EPHX1 rs1051740 (OR 0.53, p = 0.03), and A/A of CCND1 rs603965 (OR 0.44, p = 0.02). Analyses using the GS suggest that average cases have a larger number of risk alleles than controls (Student’s t test −4.85, p = 0.001; OR 1.25, p < 0.001).

Conclusions

Our results suggest significant differences between the GS for the cases and controls, which support the hypothesis underlying the additive and polygenic models for lung cancer risk depending on the polymorphisms in low-penetrance genes.

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Acknowledgments

This study was supported by grant PAPIIT-IN219807 (JR) from the UNAM and postgraduate scholarship CVU 204279 (RP) from the CONACYT. We thank Dr. Jorge Morales Fuentes and Dr. Enrique Guzmán (INER) for the blood samples and for the clinic diagnostics of the patients with cancer. We thank QFB. Miriam Balderas Morales for the recollection of blood samples and Pavel Petrosyan for careful and critical reading of the manuscript.

Conflict of interest

None declared.

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Authors and Affiliations

  1. Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Apartado Postal 70228, C.P. 04510, Mexico, D.F., Mexico

    R. Pérez-Morales, O. C. Martínez-Ramírez, C. Castro-Hernández, M. E. Gonsebatt & J. Rubio

  2. Departamento de Probabilidad y Estadística, Instituto de Investigaciones en Matemáticas Aplicadas y en Sistemas, Apartado Postal 20726, C.P. 04510, Mexico, D.F., Mexico

    I. Méndez-Ramírez

  3. División CSH de la Universidad Autónoma Metropolitana, Departamento de Economía, Unidad Iztapalapa, Av. San Rafael Atlixco 186. Col. Vicentina, C.P. 09340, Mexico, D.F., Mexico

    H. Moreno-Macias

  4. Departamento de Neumología Oncológica, Instituto Nacional de Enfermedades Respiratorias, Calzada de Tlalpan 4502, C.P. 14080, Mexico, D.F., Mexico

    A. D. Mendoza-Posadas

  5. Departamento de Biología Molecular, Facultad de Ciencias Químicas, Universidad Juárez del Estado de Durango, Av. Artículo 123 s/n. Fracc. Filadelfia, C.P. 35010, Gómez Palacio, Durango, Mexico

    R. Pérez-Morales

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  1. R. Pérez-Morales
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  2. I. Méndez-Ramírez
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  3. H. Moreno-Macias
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  5. O. C. Martínez-Ramírez
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  6. C. Castro-Hernández
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  7. M. E. Gonsebatt
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  8. J. Rubio
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Corresponding author

Correspondence to J. Rubio.

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Pérez-Morales, R., Méndez-Ramírez, I., Moreno-Macias, H. et al. Genetic Susceptibility to Lung Cancer Based on Candidate Genes in a Sample from the Mexican Mestizo Population: A Case–Control Study. Lung 192, 167–173 (2014). https://doi.org/10.1007/s00408-013-9536-7

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  • DOI: https://doi.org/10.1007/s00408-013-9536-7

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