Academic journal article Environmental Health Perspectives

Colorectal Cancer and Long-Term Exposure to Trihalomethanes in Drinking Water: A Multicenter Case-Control Study in Spain and Italy

Academic journal article Environmental Health Perspectives

Colorectal Cancer and Long-Term Exposure to Trihalomethanes in Drinking Water: A Multicenter Case-Control Study in Spain and Italy

Article excerpt

Introduction

Colorectal cancer represents nearly 10% of global cancer incidence, with increasing rates over the last decades (Bosman et al. 2014). Intake of total energy, red and processed meat, and alcoholic drinks together with physical inactivity, body fat, abdominal fat, and adult-attained height are established risk factors [Bosman et al. 2014; World Cancer Research Fund (WCRF) and American Institute for Cancer Research (AICR) et al. 2011]. Suggested protective factors include consumption of dietary fiber and high fruit and vegetable consumption (WCRF and AICR et al. 2011; Bradbury et al. 2014), among others. However, part of the burden of disease remains unexplained by the above-mentioned risk factors. Human and animal studies suggest that carcinogens in drinking water may be associated with colorectal cancer risk (Rahman et al. 2010).

Disinfection by-products (DBPs) are chemicals resulting from disinfection processes that are widespread in drinking water. Trihalomethanes (THMs) are among the most prevalent DBPs and are highly volatile and skin permeable; exposure occurs through inhalation, dermal absorption, and ingestion (Ashley et al. 2005; Gordon et al. 2006). The four THMs in drinking water that are regulated in the United States, European Union, and other countries are chloroform, bromodichloromethane, dibromochloromethane, and bromoform; these chemicals display different physicochemical and toxicological properties. Chloroform is highly volatile, whereas the other three compounds (from now on referred to as brominated THMs) are more lipophilic and genotoxic (Plewa et al. 2008). Metabolism of DBPs is mediated by enzymes from the cytochrome P450 (CYP) and glutathione 5-transferase (GST) families. In a hospital-based case-control study, polymorphisms in CYP2E1, GSTT1 and GSTZ1 were found to modify associations between bladder cancer and DBP exposure (Cantor et al. 2010).

Animal studies have suggested an association between DBP exposure and colorectal cancer. Preneoplastic lesions have been produced in the intestines of rodents administered DBPs via drinking water in chronic bioassays (DeAngelo et al. 2002; McDorman et al. 2003). However, some studies have shown that chloroform may inhibit gastrointestinal carcinogenecity in rodents (Daniel et al. 1989, 1991). Human epidemiological evidence is mixed. Case-control (Bove et al. 2007; Cragle et al. 1985; Hildesheim et al. 1998; King et al. 2000; Young et al. 1987) and cohort (Doyle et al. 1997; Koivusalo et al. 1997) studies including incident cases of colorectal cancer and quantitative estimates of exposure to DBPs such as trihalomethanes or related surrogates have produced contradictory results (see Table S1). Three studies reported positive associations with colon cancer (Cragle et al. 1985; Doyle et al. 1997; King et al. 2000), and three studies reported null associations (Hildesheim et al. 1998; Koivusalo et al. 1997; Young et al. 1987). Similarly, two studies reported positive associations with rectal cancer (Bove et al. 2007; Hildesheim et al. 1998), and three reported null associations (Doyle et al. 1997; King et al. 2000; Koivusalo et al. 1997). The exposure assessments differed, with five studies evaluating THMs (Bove et al. 2007; Doyle et al. 1997; Hildesheim et al. 1998; King et al. 2000; Young et al. 1987) and one each evaluating years living in households with chlorinated water (Cragle et al. 1985) and water mutagenicity (Koivusalo et al. 1997). The inconsistency of human epidemiological evidence might be partly attributable to exposure misclassification, including a lack of evaluation of different routes of exposure and uncontrolled confounders.

Here, we examined the association between THM exposure and colorectal cancer in a large multicenter case-control study considering specific THM components and exposure activities involving dermal contact, inhalation, and ingestion.

Methods

Study Design and Population

Spain. …

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