Use of Arsenic-Induced Palmoplantar Hyperkeratosis and Skin Cancers to Predict Risk of Subsequent Internal Malignancy

Abstract

Hyperpigmentation, hyperkeratoses, and Bowen's disease are hallmarks of chronic arsenic exposure. The association between arsenic-induced skin lesions and subsequent internal cancers is examined by using a community-based prospective study. The cohort was enrolled from an arseniasis-endemic area in southwestern Taiwan, where 2,447 residents participated in skin examinations during the late 1980s. The number of participants diagnosed with hyperpigmentation was 673; with hyperkeratosis, 243; and with skin cancer (Bowen's disease or non-melanoma skin cancer), 378. Newly diagnosed internal cancers were ascertained through linkage with National Cancer Registry profiles. Cox regression was performed to estimate hazard ratios with 95% confidence intervals for potential risk predictors. Compared with participants without skin lesions, patients affected with skin cancers had a significantly increased risk of lung cancer (hazard ratio = 4.64, 95% confidence interval: 2.92, 7.38) and urothelial carcinoma (hazard ratio = 2.02, 95% confidence interval: 1.23, 3.30) after adjustment for potential confounders and cumulative arsenic exposure. Hyperkeratosis is significantly associated with an increased lung cancer risk (hazard ratio = 2.76, 95% confidence interval: 1.35, 5.67). A significant interactive effect on lung cancer risk between hyperkeratosis and cigarette smoking was identified, which suggests that patients with hyperkeratosis who have been exposed to arsenic should cease smoking.

Arsenic and Lung Disease Mortality in Bangladeshi Adults

“…Skin lesion severity itself is a construct that represents a composite of the extent of arsenic exposure (including potentially cumulative exposure effects) and susceptibility (e.g., genetic, nutritional) to exposure. Skin lesion status as a predictor of disease risk was an approach recently taken by Hsu et al 27 in their analyses of internal cancer risk, as well as by us to examine chronic disease co-morbidities. 28 …”

“…36 For the purposes of this analysis, we evaluated baseline skin lesion status as a proxy measure of cumulative arsenic exposure, as well as susceptibility to exposure. 27 Analyses were conducted by the presence of any skin lesion, which included 839 (4%) prevalent skin lesions among participants from the arsenic study and 6,834 (100%) prevalent skin lesions among participants from the vitamin trial. Analyses were also conducted by skin lesion severity, classified as less-severe skin lesions with no keratosis (melanosis and/or leucomelanosis only) if no body segment had keratotic lesions (n=3,133) and more-severe skin lesions with keratosis if one or more body segments had keratotic lesions (n=3,701).…”

“…26 Furthermore, previous epidemiologic studies have shown that persons with arsenical skin lesions or skin cancers are at increased risk of internal cancers and other chronic disease conditions. 27,28 …”

The Role of Arsenic on Skin Diseases, Hair Fall and Inflammation: An Immunological Review and Case Studies

“…Arsenic has also been observed as a hallmark of several diseases like hyperpigmentation, hyperkeratoses, and Bowen's disease. Chronic arsenic exposure to patients who were previously suffering from either hyperpigmentation or hyperkeratosis or Bowen's disease found to be more prone to have lung cancer [36]. Epigenetic modifications of the tumor suppressor genes with dermatological and non-dermatological subject's health, methylation status of p16 and DAPK genes were determined which linked with other life threatening conditions ( Figure 1) [37].…”

Subchronic Early Life Arsenic Exposure at Low Doses Impaired the Biogenic Amine Neurotransmitter and Nitric Oxide Levels in Different Brain Regions of Rats

“…Arsenic is a major global health alarm due to its wide distribution and adverse health effects on the human body. The people of the large portions of the world are being exposed to arsenic through drinking water or ingestion of food materials and causing serious health effects involving the dermal, gastrointestinal, nervous, hepatic, renal, cardiovascular, respiratory, hematopoietic and ophthalmic systems [3][4][5][6][7][8]. In contrast to other physiological systems of the body, the nervous system appears to be the most vulnerable and the main target for arsenicinduced neurotoxicity [9].…”