Two Gene Variations Predict Aggressiveness of Gastric Cancer

ORLANDO, FL—Gastric cancer is the fourth most common cancer type and the second cause of cancer death worldwide. Pathogenesis of gastric cancer is multifactorial, including genetic and environmental factors. At the 2010 Gastrointestinal Cancers Symposium, investigators reported that they have for the first time identified inherited genetic variations that are predictive of more aggressive disease in patients with gastric adenocarcinomas. Patients with these variations, located on the CD44 gene, experienced tumor recurrence more than three times earlier than those without them. The study was included in a press cast released prior to the meeting and deemed a significant clinical advance.

In an earlier study, the investigators had shown that germline polymorphisms in angiogenic pathways may serve as independent molecular prognostic markers in patients with localized gastric adenocarcinomas. The current study assessed whether germline variations in CD44 will predict clinical outcomes in patients with localized gastric adenocarcinomas. The CD44 gene regulates the production of a protein associated with cell adhesion, the loss of which is associated with cancer development and metastasis in digestive cancers.

DNA was isolated from peripheral blood samples collected from 137 patients treated for localized gastric cancer at the University of Southern California medical facilities and assessed for standard (wild-type) or four cell-adhesion related polymorphisms within the CD44 gene. The effect of these polymorphisms on time to tumor recurrence (TTR) and overall survival (OS) was examined.

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Researchers found that patients carrying at least one G allele (A/G or G/G) at the CD44 4883G>A gene locus had a significantly shorter median TTR at 2.1 years compared with 7.0 years for patients with the wild-type A/A genotype (log-rank = .022). These patients also had a shorter OS at 4.1 years compared with 7.0 years for those with the wild-type A/A genotype (log-rank = .079). Similar results were observed for patients carrying at least one A allele (A/G or A/A) at the CD44 779G>A gene locus, with these patients having a TTR of 2.2 years versus 7.0 years (log-rank = .045) and an OS of 3.8 years versus 7.3 years (log-rank = .018) compared with those with wild-type G/G genotypes. No statistically significant association was found between the two other polymorphisms examined and TTR and OS.

According to the study’s lead investigator, Thomas Winder, MD, postdoctoral research fellow at the University of Southern California, “If our findings are confirmed in larger, prospective clinical trials, testing for the CD44 variation could help us identify patients who would benefit from more aggressive treatment, as well as facilitate the development of therapies targeting this genetic variation.” Because the genetic variation is inherited, this finding also could be used to develop a genetic test to predict an individual’s risk of developing gastric cancer. Winder cautioned, however, that epidemiological studies need to be conducted to further characterize and confirm the role of this genetic variation in gastric cancer development.

(Note: Abstract does not reflect the latest data)

2010 GI Symposium Abstract 2