Bladder cancer patients who have been exposed to high levels of environmental arsenic may have a lower risk of death compared with those exposed to low levels, according to researchers.

The investigators analyzed levels of arsenic exposure and the clinical course of 832 New Hampshire residents with bladder cancer. Individuals exposed to high levels of arsenic in the environment were half as likely to die as those exposed to low levels, researchers reported in the World Journal of Urology (2009; published online ahead of print).

The effect was the similar for invasive and noninvasive tumors. While high toenail arsenic levels as an internal biomarker was associated with longer overall survival, the association with drinking water levels and the trend observed for bladder cancer-specific deaths were not statistically significant. The investigators also analyzed smokers and non-smokers separately. They found that the protective effect of high levels of arsenic exposure applied to smokers but not to non-smokers.

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“Arsenic exposure history may modify the phenotype and prognosis of a tumor,” said lead investigator Angeline Andrew, PhD, Assistant Professor of Community and Family Medicine, Dartmouth Medical School, Lebanon, N.H. “In the future, we can hopefully find out which treatments work best in these arsenic-exposed individuals.”

The concept that arsenic exposure may impact cancer mortality is not new. A study published in 1992 showed that two-thirds of patients with acute promyelocytic leukemia enrolled in a clinical trial went into remission after receiving inorganic trivalent arsenic (Chi J Integrat Chin West Med. 1992;12:170-172).

A later study demonstrated a similar effect in multiple myeloma and lymphoma (J Natl Cancer Inst. 1999;91:772-778). Recently, however, investigators reported that the use of arsenic trioxide at a dosage of 0.3 mg/kg for five days every 28 days in patients with recurrent urothelial cancer did not reduce mortality and was associated with substantial toxicity (Clin Genitourin Cancer. 2009;7:E66-E70).

This suggests that arsenic treatment post-diagnosis is not effective. The longer survival observed in the New Hampshire study may be explained by chronic arsenic exposure inducing development of less aggressive tumor type. 

Dr. Andrew and her co-investigators used the state cancer registry to identify all of the New Hampshire residents aged 25 to 74 years who were diagnosed with bladder cancer between July 1994 and December 2001. They asked subjects for sociodemographic information and obtained toenail clippings to determine arsenic exposure levels. A pathologist re-reviewed the subjects’ tumor tissue samples to confirm the histology, stage and grade.