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

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 5.002). Leukocyte mtDNA copy numbers were significantly lower in GC cases (mean 6 standard deviation, 0.91 6 0.28) than in controls (1.29 6 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 5.551). CONCLUSIONS: Hispanics share certain genetic susceptibility loci and intermediate phenotypic GC biomarkers with whites and Asians and may also have distinct genetic susceptibility factors.

PSCA s2294008 C>T and rs2976392 G>A polymorphisms contribute to cancer susceptibility: evidence from published studies

“…The studied cancer type included gastric cancer [8, 14-17, 20-22, 25, 26, 31, 32, 34, 39, 41-43], bladder cancer [9, 18, 23, 28, 35, 40], prostate cancer [19], esophageal cancer [20, 33], breast cancer [24], colorectal cancer [27], and gallbladder cancer [29, 30]. In term of ethnicity, 21 studies were performed among Asians, 10 studies among Caucasians, and one study among Africans.…”

A rising trend in the incidence of advanced gastric cancer in young Hispanic men

“…Obesity has been associated with the development of various cancers of the gastrointestinal tract, including gastric cancer (27), and with obesity rates on the rise in the young (28), this may increase rates of gastric cancer. Third, genetic susceptibility also merits consideration as a recent case-control study identified the presence of certain single nucleotide polymorphisms as loci for susceptibility to gastric cancer in Hispanic Americans (29). Finally, differences in tumor biology may also be implicated as Hispanics have previously been shown to have increased incidence of mucinous/signet cell histology, involvement of the whole stomach, and peritoneal dissemination (30).…”

High mitochondrial DNA copy number was associated with an increased gastric cancer risk in a Chinese population

“…Two case‐control studies have reported the relationship between mtDNA copy number in leukocyte and gastric cancer risk to date. Sun et al conducted a study in 132 gastric cancer cases and 125 controls of a Hispanic population and found significant association between low mtCN and increased gastric cancer risk (OR = 11.00; 95%CI = 4.79‐25.23), when individuals were dichotomized into high and low mtCN groups based on the median mtCN value in the controls. They also examined the association of leukocyte telomere length with the risk of gastric cancer, and found no significant association between short telomere length and increased gastric cancer risk.…”

“…However, the association between mtCN and gastric cancer remains conflicting. Pilot data from a recent retrospective case‐control study in Hispanic Americans showed that low mtCN was associated with increased risk of gastric cancer . Yet, a prospective study of Chinese women found no association between leukocyte mtCN and risk of gastric cancer …”

“…Pilot data from a recent retrospective case-control study in Hispanic Americans showed that low mtCN was associated with increased risk of gastric cancer. 27 Yet, a prospective study of Chinese women found no association between leukocyte mtCN and risk of gastric cancer. 28 In the current study, we tested for association between peripheral leukocytes mtCN and gastric cancer risk in 984 gastric cancer patients and 984 age and sex frequency-matching controls.…”