title: Genetic susceptibility to lung cancer based on candidate genes in a sample from the Mexican Mestizo population: a case-control study.
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.
authors.affiliation: 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.
authors.forename: R
authors.initials: R
authors.lastname: Pérez-Morales
authors.forename: I
authors.initials: I
authors.lastname: Méndez-Ramírez
authors.forename: H
authors.initials: H
authors.lastname: Moreno-Macias
authors.forename: A D
authors.initials: AD
authors.lastname: Mendoza-Posadas
authors.forename: O C
authors.initials: OC
authors.lastname: Martínez-Ramírez
authors.forename: C
authors.initials: C
authors.lastname: Castro-Hernández
authors.forename: M E
authors.initials: ME
authors.lastname: Gonsebatt
authors.forename: J
authors.initials: J
authors.lastname: Rubio
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D016015:Logistic Models; D008175:Lung Neoplasms / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D016017:Odds Ratio; D019683:Penetrance; D010641:Phenotype; D011110:Polymorphism, Genetic; D012307:Risk Factors; D055815:Young Adult