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Background: The incidence of cancer was determined by genetic and environmental factors and varied across the world. The discrepancies in cancer profile among Chinese people living in different regions remained obscure., Methods: Chinese people living in urban Shanghai, Hong Kong, Taiwan, Macau, Singapore, and Los Angeles were included in this study. The cancer case data and population data were collected from either the Cancer Incidence in Five Continents Plus database or the regional cancer registry. A rate model was applied to examine the regional differences in cancer risk with Shanghai set as the reference., Results: From 1983 to 2013, the cancer profiles in most regions were changed. Significant differences in cancer incidence, by sex, period, and age, were detected across regions. The most pronounced disparities were found between Shanghai people and American Chinese in Los Angeles. For cancer site, the most significant differences were detected in prostate, gastrointestinal, gynecologic, oral cavity and pharynx, and brain and central nervous system (CNS) cancers. Specifically, Shanghai was significantly higher in stomach, liver, esophageal, pancreatic, and brain and CNS cancers, while lower in colon, prostate, breast, cervical, and oral cavity and pharynx cancers compared with the other five populations., Conclusions: Cancer profile was distinct across Chinese populations, which shared a similar genetic background but lived in different regions. The disparities indicate that cancer development was majorly determined by environmental factors, and suggests that region-tailored cancer prevention strategies were warranted., Impact: The cancer patterns in populations sharing the same genetic background were significantly influenced by different living conditions., (©2019 American Association for Cancer Research.)