Certain genetic variants increase recurrence risk for bladder cancer

Inheriting certain DNA sequences can affect the prognosis of bladder cancer patients, according to a new study. The findings may help physicians identify sub-groups of bladder cancer patients who should receive intensive treatment and monitoring.

In the Western world, bladder cancer is the fourth most common cancer in men and the eighth most common in women, with many patients experiencing recurrence after treatment. Nearly half of patients with bladder cancer experience tumor recurrences, but predicting which patients are at risk is difficult.

Angeline Andrew, PhD, of the Dartmouth-Hitchcock Norris Cotton Cancer Center in Lebanon, New Hampshire, and her colleagues analyzed the genes of 563 patients to identify genetic variants that modify time to bladder cancer recurrence and patient survival. The investigators isolated DNA from immune cells circulating in the blood, and they examined genes involved in major biological processes linked to cancer: cell death, proliferation, DNA repair, hormone regulation, immune surveillance, and cellular metabolism.

After diagnosis, patients were followed over time to ascertain recurrence and survival status. Patients were followed for a median of 5.4 years, and half of patients experienced at least one recurrence.

The team found that patients with variants in the aldehyde dehydrogenase 2 (ALDH2) gene were likely to experience bladder cancer recurrence shortly after treatment. This gene encodes an enzyme involved in alcohol metabolism.

Time to recurrence was also shorter for patients who had a variant in the vascular cellular adhesion molecule 1 (VCAM1) gene and were treated with immunotherapy. VCAM1 encodes a glycoprotein involved in the development of lymphoid tissues. Patients who had noninvasive tumors and a variant in the DNA repair gene XRCC4 tended to live longer than patients who did not have the variant.

The researchers noted that the novel associations between genetic variants and bladder cancer recurrence uncovered in this study merit future investigation. "The genetic markers that we found could potentially be useful for individually tailoring surveillance and treatment of bladder cancer patients," said Andrew. The study was published in BJU International (2014; doi:10.1111/bju.12641).

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