CD44 POLYMORPHISM AND GASTRIC CANCER SURVIVAL

ORLANDO (Reuters Health) Jan 25 - Patients with gastric cancer who have a germline polymorphism in the CD44 gene have much more aggressive disease and are at higher risk for tumor recurrence than patients without this variation, according to new research presented at the American Society of Clinical Oncology's 2010 Gastrointestinal Cancers Symposium.

Being able to identify such patients could help guide their treatment and hopefully improve outcomes, said Dr. Thomas Winder, a postdoctoral research fellow at the University of Southern California Norris Comprehensive Cancer Center, Los Angeles.

The CD44 gene regulates the production of a protein associated with cellular adhesion and metastasis in digestive cancers, and high CD44 protein expression has been associated with poor prognosis, Dr. Winder explained. Altered CD44 may also make cancer cells more resistant to chemotherapy or radiation therapy.

The goal of his research was to discover whether germline variations within the CD44 gene are linked to clinical outcome in patients with localized gastric adenocarcinoma.

In 104 patients (63 males) with a median age of 57 years (range, 26 to 85), Dr. Winder and his colleagues sought to determine whether 4 genetic variations in the CD44 gene were associated with time to recurrence and overall survival.

They found that patients with the wild type A/A genotype in the first CD44 polymorphism (CD44 + 4883G>A) had a significantly longer time to tumor recurrence -- a median of 7.0 years after their diagnosis of resectable gastric cancer -- compared with just 2.1 years in patients who had the variant A/G or G/G genotypes (Log-Rank P value = 0.022).

Patients with the wild type A/A genotype also had longer median overall survival: 7 years, compared with 4.1 years for those with the A/G or G/G genotype (Log-Rank P value = 0.079).

These associations were also true for the second CD44 polymorphism (CD44 + 779G>A). Patients with the wild type G/G genotype had a significantly improved median time to tumor recurrence -- 7 years -- compared with 2.2 years for patients with the A/G or A/A genotype (Log-Rank P value = 0.045).

Median overall survival was 7.3 years for the wild type G/G genotype compared with 3.8 years for the variant A/G or G/G genotypes (Log-Rank P value = 0.018).

"Our results have clinical significance because we can now identify, with two single-nucleotide polymorphisms, those patients who are at high risk for tumor recurrence or metastasis. These patients might benefit from more aggressive treatment," Dr. Winder commented to Reuters Health.

"The CD44 test is reliable and the technique is available now, that's not a big deal. You have to collect blood, isolate the DNA, and then use PCR, which is available in every lab, to do the test. It's not expensive," he said.

But, he cautioned, "Our data are preliminary and have to be validated in prospective biomarker embedded clinical trials before they have immediate impact in actual clinical practice."