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. 2011 Oct;34(4):546-52.
doi: 10.1590/S1415-47572011005000053. Epub 2011 Oct 1.

Polymorphisms associated with the risk of lung cancer in a healthy Mexican Mestizo population: Application of the additive model for cancer

Rebeca Pérez-Morales  1 , Ignacio Méndez-Ramírez, Clementina Castro-Hernández, Ollin C Martínez-Ramírez, María Eugenia Gonsebatt, Julieta Rubio
Affiliations

Polymorphisms associated with the risk of lung cancer in a healthy Mexican Mestizo population: Application of the additive model for cancer

Rebeca Pérez-Morales et al. Genet Mol Biol. 2011 Oct.

Abstract

Lung cancer is the leading cause of cancer mortality in Mexico and worldwide. In the past decade, there has been an increase in the number of lung cancer cases in young people, which suggests an important role for genetic background in the etiology of this disease. In this study, we genetically characterized 16 polymorphisms in 12 low penetrance genes (AhR, CYP1A1, CYP2E1, EPHX1, GSTM1, GSTT1, GSTPI, XRCC1, ERCC2, MGMT, CCND1 and TP53) in 382 healthy Mexican Mestizos as the first step in elucidating the genetic structure of this population and identifying high risk individuals. All of the genotypes analyzed were in Hardy-Weinberg equilibrium, but different degrees of linkage were observed for polymorphisms in the CYP1A1 and EPHX1 genes. The genetic variability of this population was distributed in six clusters that were defined based on their genetic characteristics. The use of a polygenic model to assess the additive effect of low penetrance risk alleles identified combinations of risk genotypes that could be useful in predicting a predisposition to lung cancer. Estimation of the level of genetic susceptibility showed that the individual calculated risk value (iCRV) ranged from 1 to 16, with a higher iCRV indicating a greater genetic susceptibility to lung cancer.

Keywords: Mexicans; additive model; genetic polymorphism; lung cancer; molecular epidemiology.

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Figures

Figure 1
Figure 1
Conglomerate analysis showing the genetic heterogeneity of the population studied in this work. C – cluster number, n – number of individuals per cluster and P – the probability of each cluster. Only under-represented genotypes are shown.
Figure 2
Figure 2
Hierarchical cluster analysis of the different genotypes based on the genetic characteristics of healthy Mexican Mestizos. r = 0.94939. *Allelic frequencies of the polymorphic genotypes.
Figure 3
Figure 3
Estimated risk of lung cancer in a healthy Mexican Mestizo population. The arrow indicates the 85th percentile.
See this image and copyright information in PMC

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Internet Resources

    1. GenePop statistical package. http://genepop.curtin.edu.au(October 5, 2010)