Arsenic and Cancer: A Crisis in Bangladesh

A substantial increase in worldwide cancer deaths has been projected for the next decade, one that is largely attributed to increased cancer deaths in developing countries. (1) Although cancer may not have formerly been a prominent contributor to the health burden of developing countries, several elements have caused this shift, including increased longevity, adoption of a Western lifestyle. and exposure to environmental carcinogens.(2) For Bangladesh, a developing country in Southeast Asia, it is this last element that is now driving cancer to become a leading public health concern for its population.

Maria Argos, MPH

In the 1990s, it was first discovered that the population of Bangladesh had been drinking groundwater that was naturally contaminated from the surrounding geologic rock with high levels of arsenic. This became evident when a previously unknown epidemic of classical arsenic-related premalignant skin lesions began to surface among the population. Nationwide surveys established that nearly half of the roughly 10 million hand-pumped tube wells serving 95% of the 140 million Bangladeshis were yielding contaminated groundwater.(3) Although the exact time of onset of high arsenic exposure in Bangladesh is unknown, it is believed to

have started during the 1960s and 1970s when the United Nations Children’s Fund (UNICEF), in collaboration with the country’s government at the time, began to install hand-pumped tube wells on a national scale to provide pathogen-free drinking water to the population, which had long had alarmingly high incidence and mortality rates of waterborne diseases.

Arsenic is classified as an established human carcinogen by the International Agency for Research on Cancer. Epidemiologic studies have provided substantial evidence for the association of arsenic in drinking water with cancers of the skin (non-melanoma), lung, and bladder. Limited epidemiologic evidence also suggests a possible association of arsenic in drinking water with cancers of the liver, kidney, and prostate.(4)

Because arsenical skin lesions are considered precursors of arsenic-induced basal and squamous cell skin cancers, prevention and treatment of these premalignant skin lesions are an important public health issue. The human health effects of arsenic exposure from drinking water are a major public health issue not only in Bangladesh but in other countries worldwide, including the US, China, Chile, Argentina, Australia, Mexico, Taiwan, Vietnam, and West Bengal (India). It is estimated that over 100 million people in the world are chronically exposed to arsenic through drinking water.(5)

Scientific evidence is sparse regarding the effects of low-level arsenic exposure. Our knowledge about the health effects of arsenic exposure at doses less than 100 µg/liter is based primarily on extrapolations from high-dose studies. Most of the studies conducted to date, including cohort studies, have used retrospective ecologic exposure measurements in their dose-response analyses because either the exposure had ceased many years before the studies were conducted or the population drank water from multiple sources, making assessment of individual-level exposure extremely difficult. There is substantial evidence of the cancer risk associated with arsenic in drinking water; however, the worldwide burden of this risk is yet to be fully realized since many questions remain unanswered.

Since millions of people in the Bangladeshi population have already accrued decades of chronic arsenic exposure, a worsening epidemic of arsenic-induced cancers in Bangladesh is inevitable. Long-term studies from Taiwan have shown that once chronically exposed, an arsenic-exposed population continues to experience an elevated risk of cancers even several decades after the exposure has ceased.(6) By extrapolating the dose-specific risk estimates observed in Taiwan to the population of Bangladesh, we have estimated that the lifetime risk of deaths due to arsenic-induced cancers in the Bangladeshi population are at least doubled because of the arsenic problem.(7) Thus, our research suggests that, in addition to the efforts to provide the Bangladeshi population with arsenic-free water, auxiliary interventions should focus on reducing the persistence of the cancer risk related to arsenic.

There is a particular need to systematically assess the cofactors associated with increased arsenic-induced cancer risk. Arsenical skin lesions (i.e., melanosis, leucomelanosis, and keratosis) are a hallmark of chronic arsenic toxicity. Unlike arsenic-induced cancers, which have a long latency (i.e., decades), these skin lesions may appear within a few years of exposure. We and others have demonstrated marked interindividual variability in susceptibility to the adverse effects of arsenic exposure from drinking water in association with other factors. Specifically, the risk of arsenic-induced skin lesions and cancers is greater among men than in women. Both tobacco smoking and ultraviolet radiation have been identified as independent risk factors of non-melanoma skin cancer, and contributors to the higher risk of arsenic-related skin lesions in men. Other lifestyle factors or occupational exposures, including nutritional status, socioeconomic status, and genetic factors, also have been shown to modify the effects of arsenic exposure on skin lesions and cancer.(8--11)

In 2000, researchers from Columbia University in New York, in collaboration with local Bangladeshi scientists, initiated the Health Effects of Arsenic Longitudinal Study (HEALS), a prospective cohort study of nearly 12,000 men and women in Araihazar, Bangladesh, to investigate the health effects of arsenic exposure, with an initial focus on premalignant and malignant skin lesions and to establish a biorepository for future studies.(12) Although this work is ongoing, we observed a dose-response relationship with arsenic exposure and premalignant skin lesion risk, indicating increased risk at levels far below the current World Health Organization (WHO) and US Environmental Protection Agency (EPA) standards for arsenic in drinking water.

Data from the HEALS cohort has provided evidence on possible chemoprevention strategies. We have found, through dietary and blood measures, that selenium and other antioxidants are associated with a reduced risk of skin lesions. Our research also shows that selenium reverses molecular alterations induced by arsenic.(12--14) Thus, in 2005, we began a chemoprevention trial to examine the effect of selenium and vitamin E supplementation in individuals with arsenical skin lesions. The study aims to evaluate the effect of vitamin E and selenium supplementation on the incidence of non-melanoma skin cancer and cancer-related mortality, incidence and progression of prevalent skin lesions, and levels of oxidative DNA damage using a two-by-two factorial, double-blind, placebo-controlled design among 5,000 individuals with manifest arsenical premalignant skin lesions. It is hoped that this ongoing trial, the largest and most comprehensive study to prevent cancer among population with high risk for environmentally-induced cancer, will provide evidence for the use of dietary supplements as a feasible and affordable strategy in the reduction of arsenic-induced cancers and their deaths.

In conclusion, much has been learned about the carcinogenicity of arsenic in drinking water from the growing body of epidemiologic evidence. It is now imperative for public health advocates, scientists, and governmental and non-governmental organizations to work together to formulate these and future data into practical public health policy.