The objective of this study was to examine multiple risk factors and correlated malignant neoplasms of blackfoot disease (BFD), a unique peripheral vascular disease related to continuous exposure to high-arsenic artesian well water. A total of 241 BFD cases, Including 169 with spontaneous or surgical amputations of affected extremities, and 759 age-sex-resldence-matched healthy community controls were studied to explore the risk factors of BFD. Multiple logistic regression analysis showed that artesian well water consumption, arsenic poisoning, familial history of BFD, and undernourishment were significantly associated with the development of BFD. The life-table method used to analyze cancer mortality of 789 BFD patients followed for 15 years showed a significantly higher mortality from cardiovascular diseases, peripheral vascular diseases, and cancers of bladder, skin, lung, and liver among BFD patients as compared with the general population In Taiwan 1 Clinically the disease starts with numbness or coldness of one or more extremities and intermittent claudication which progress to black discoloration, ulceration, and gangrene. In trie end stages of the disease, spontaneous or surgical amputations of distal parts of affected extremities are common.2 Extensive pathological study showed that 30% of BFD patients had histological lesions compatible with thromboangiitis obliterans and 70% showed changes of arteriosclerosis obliterans.3 BFD has long been related to the drinking water derived from artesian wells in the endemic area; 4 -7 however, the etiology of this disease still remains unclear. While artesian well water was commonly used in the BFD-endemic area, the prevalence of the disease was only 8.9 per 1000 at most. 7 The lifetime cumulative incidence rate of BFD was estimated to be less than 10% among those who drank artesian well water.8 It is important to explore the reason why most residents who consumed artesian well water were free of the disease. Both fishermen and salt-field workers had significantly higher

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