Genetic and intermediate phenotypic susceptibility markers of gastric cancer in Hispanic Americans: a case-control study

Cancer. 2014 Oct 1;120(19):3040-8. doi: 10.1002/cncr.28792. Epub 2014 Jun 24.

Abstract

Background: Hispanics are the largest nonwhite ethnic group in the US population, and they have higher incidence and mortality rates for gastric cancer (GC) than whites and Asians. Studies have identified several genetic susceptibility loci and intermediate phenotypic biomarkers for GC in whites and Asians. No studies have evaluated genetic susceptibility and intermediate phenotypic biomarkers in Hispanics.

Methods: In a case-control study of 132 Hispanic patients with GC (cases) and a control group of 125 Hispanics (controls), the authors evaluated the association of 5 single nucleotide polymorphisms (SNPs) that predispose whites and/or Asians to GC and of 2 intermediate phenotypic markers in peripheral blood leukocytes, ie, telomere length and mitochondrial DNA (mtDNA) copy number, with the GC risk.

Results: The variant C allele of the reference SNP rs2294008 in the PSCA gene was associated with a significantly reduced risk of GC (per allele-adjusted odds ratio [aOR], 0.51; 95% confidence interval [CI], 0.33-0.77; P = .002). Leukocyte mtDNA copy numbers were significantly lower in GC cases (mean ± standard deviation, 0.91 ± 0.28) than in controls (1.29 ± 0.42; P < .001). When individuals were dichotomized into high and low mtDNA copy number groups based on the median mtDNA copy number value in the controls, those who had a low mtDNA copy number had a significantly increased risk of GC (aOR, 11.00; 95% CI, 4.79-25.23; P < .001) compared with those who had a high mtDNA copy number. Telomere length was not associated significantly with the risk of GC (aOR, 1.21; 95% CI, 0.65-2.27; P = .551).

Conclusions: Hispanics share certain genetic susceptibility loci and intermediate phenotypic GC biomarkers with whites and Asians and may also have distinct genetic susceptibility factors.

Keywords: Hispanics; copy number; gastric cancer; mitochondrial DNA; single nucleotide polymorphism; telomere length.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / genetics
  • Adult
  • Aged
  • Antigens, Neoplasm / genetics
  • Case-Control Studies
  • DNA Copy Number Variations*
  • DNA, Mitochondrial
  • Female
  • GPI-Linked Proteins / genetics
  • Genetic Markers*
  • Genetic Predisposition to Disease
  • Hispanic Americans / genetics*
  • Humans
  • Leukocytes*
  • Logistic Models
  • Male
  • Middle Aged
  • Mucin-1 / genetics
  • Neoplasm Proteins / genetics
  • Nerve Tissue Proteins / genetics
  • Odds Ratio
  • Phenotype
  • Phosphoinositide Phospholipase C / genetics
  • Polymorphism, Single Nucleotide*
  • Real-Time Polymerase Chain Reaction
  • Stomach Neoplasms / epidemiology
  • Stomach Neoplasms / genetics*
  • Telomere*
  • Transcription Factors / genetics
  • United States / epidemiology

Substances

  • Antigens, Neoplasm
  • DNA, Mitochondrial
  • GPI-Linked Proteins
  • Genetic Markers
  • MUC1 protein, human
  • Mucin-1
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • PSCA protein, human
  • Transcription Factors
  • ZBTB20 protein, human
  • PRKAA1 protein, human
  • AMP-Activated Protein Kinases
  • Phosphoinositide Phospholipase C
  • phospholipase C epsilon