Obesity and excess weight in early adulthood and high risks of arsenic-related cancer in later life
Introduction
Tens of millions of people worldwide are exposed to arsenic-contaminated drinking water. Ingested arsenic is an established cause of skin, bladder, and lung cancer, and has been linked to diabetes, and cardiovascular and lung disease (IARC, 2012). Cancer risk from arsenic is very high, and the National Research Council has estimated that the cancer risk associated with the US standard for arsenic in drinking water of 10 µg/L may be as high as 1 in 300 (NRC, 2001). This is more than an order of magnitude higher than the risks estimated for any other regulated drinking water carcinogen (Smith et al., 2002). Susceptibility to arsenic varies widely from person to person, and risks may be even higher in certain susceptible sub-populations. Inter-individual differences in diet, arsenic metabolism, co-exposures, and genetics have all been linked to increased risks, but to date most of the variability in susceptibility remains unexplained (National Research Council, 2014).
The primary toxic mechanism of arsenic is unknown, but may involve inflammation or oxidative stress. Arsenic has been linked to biomarkers of oxidative stress and inflammation, alterations in immune status, and inflammatory and infectious diseases such as bronchiectasis, respiratory infections, and tuberculosis (Ahmed et al., 2011, Guha Mazumder et al., 2005, Ramsey et al., 2013, Smith et al., 2011). Elevated body mass indices (BMI) also increase oxidative stress and inflammation and has been linked to some, albeit not all, cancer types (Pergola and Silvestris F., 2013, Marseglia et al., 2015). Given the common link to oxidative stress, inflammation, and cancer, we hypothesized that arsenic and elevated BMI may interact, to increase cancer risk. We evaluated this hypothesis using data from a cancer case-control conducted in high arsenic-exposed populations of the Atacama Desert area of northern Chile (Steinmaus et al., 2013). Previously, we and others have identified high risks of lung cancer, bladder cancer, cardiovascular disease, and other health outcomes in this area (Smith et al., 2012). The present study is to our knowledge the first to evaluate the potential impact of elevated BMI on arsenic-related cancer risk.
Section snippets
Study area
Study design details are published elsewhere (Steinmaus et al., 2013). Briefly, the study area comprises two contiguous regions (Regions I and II) in northern Chile. This area lies within the Atacama Desert, one of the driest places on earth. Because of its dryness, most people live in one of the cities or small towns and receive drinking water from municipal supplies. Records of past arsenic concentrations in the water supplies are available for several past decades, and have ranged from <10
Results
Cancer cases tended to be heavier smokers and had a greater arsenic exposure than controls but were not markedly different in terms of race (after arsenic adjustment), mining work, and SES (Table 1). Drinking water intake and fruit and vegetable consumption were higher in cases but differences were small. For BMI at age 20, the 90th percentile was 27.7 kg/m2 in men and 28.6 kg/m2 in women. BMI ranges below and above the 90th percentile at age 20 were 14.5–27.7 and 27.7–51.1 kg/m2 for men, and
Discussion
Our findings of higher arsenic-related cancer ORs in subjects with higher BMIs, with an over 4-fold increase in the Rothman Synergy Index, provide evidence that arsenic and excess BMI interact in a greater than additive manner to increase arsenic-related cancer. The low p-values and confidence intervals with lower bounds >1.0 are evidence that these findings are unlikely due to chance. The fairly consistent findings for both bladder and lung cancer, across different measures of arsenic
Conclusions
These findings are the first evidence that excess BMI may be associated with large increases in the cancer risks related to a common environmental chemical exposure. Given the worsening epidemic of obesity and elevated BMI in many countries, and the very widespread nature of arsenic exposure, these findings could have important public health implications. Importantly though, our results are quite novel and sample sizes were small in some analyses. As such, these findings are preliminary and
Disclaimer
The views in this paper do not necessarily reflect those of the Office of Environmental Health Hazard Assessment or the California Environmental Protection Agency.
Conflict of interests
Dr. Steinmaus has done consulting work on arsenic toxicity for both industry and environmental groups. The other authors have no conflict of interests.
Acknowledgments
This research was supported by US National Institute of Environmental Health Sciences grants 5R01ES014032 and P42ES04705.
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