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// Pian Liu 1, Shao-Hua Xie 2, Shaobo Hu 3, Xiang Cheng 3, Tianyi Gao 4, Chen Zhang 3 and Zifang Song 3 1 Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China 2 Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm 17176, Sweden 3 Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China 4 The First Clinical Medical School, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China Correspondence to: Chen Zhang, email: zhangchen@hust. edu. cn Keywords: hepatocellular carcinoma, liver cancer, sex difference, incidence, estrogen Received: February 28, 2016 Accepted: June 11, 2017 Published: July 12, 2017 ABSTRACT Background: Hepatocellular carcinoma possesses a notable sex difference in incidence, and a protective role of estrogens has been hypothesized. Methods: Using data from 13 cancer registries in the Surveillance, Epidemiology, and End Results Program, we describe the age-specific sex difference in the incidence of hepatocellular carcinoma in the United States during 1992-2013. We used a curve fitting by non-linear regression to quantitatively characterize the age-specific incidence rate of hepatocellular carcinoma by sex. Results: A total of 44, 287 incident cases of hepatocellular carcinoma (33, 196 males and 11, 091 females) were included, with an overall male-to-female ratio in age-standardized rate of 3. 55. The sex ratio was below 2 at ages <25 years, increased with age from ages 25-29 years until peaking at 5. 40 at ages 50-54 years, and declined thereafter. We also observed additional peaks in the age-specific sex ratio curves at ages 25-34 years across racial/ethnic groups. Modelling of age-specific incidence rates indicated a 15-year delayed increase with age in females compared with males in Asian and Pacific Islanders, and an 11-year delay in Hispanic whites. Conclusions: The age-dependent patterns in the sex difference in the incidence of hepatocellular carcinoma support the hypothesis of a protective role of estrogens. The underlying reasons for the sex difference in hepatocellular carcinoma remain to be further explored in analytic epidemiological studies.
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