Manal M Hassan1, Gehan Botrus2, Reham Abdel-Wahab3, Robert A Wolff2, Donghui Li2, David Tweardy4, Alexandria T Phan5, Ernest Hawk6, Milind Javle2, Ju-Seog Lee7, Harrys A Torres8, Asif Rashid9, Renato Lenzi2, Hesham M Hassabo2, Yasmin Abaza2, Ahmed S Shalaby2, Sahin Lacin10, Jeffrey Morris11, Yehuda Z Patt12, Christopher I Amos13, Saira A Khaderi14, John A Goss14, Prasun K Jalal15, Ahmed O Kaseb2. 1. Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: mhassan@mdanderson.org. 2. Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas. 3. Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Clinical Oncology, Assiut University Hospital, Assiut, Egypt. 4. Division of Internal Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas. 5. Houston Methodist Hospital, Houston, Texas. 6. Division of Cancer Prevention and Population Science, the University of Texas MD Anderson Cancer Center, Houston, Texas. 7. Department of System Biology, the University of Texas MD Anderson Cancer Center, Houston, Texas. 8. Department of Infectious Diseases, the University of Texas MD Anderson Cancer Center, Houston, Texas. 9. Department of Pathology, the University of Texas MD Anderson Cancer Center, Houston, Texas. 10. Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Medical Oncology, Hacettepe University, Ankara, Turkey. 11. Department of Biostatistics, the University of Texas MD Anderson Cancer Center, Houston, Texas. 12. University of New Mexico Health Sciences Center, Albuquerque, New Mexico. 13. Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire. 14. Michael E. DeBakey Department of Surgery, Division of Abdominal Transplantation and Hepatobiliary Surgery, Baylor College of Medicine, Houston, Texas; Department of Surgery, Texas Children's Hospital, Houston, Texas. 15. Michael E. DeBakey Department of Surgery, Division of Abdominal Transplantation and Hepatobiliary Surgery, Baylor College of Medicine, Houston, Texas.
Abstract
BACKGROUND & AIMS: Environmental factors have been identified that affect risk of hepatocellular carcinoma (HCC), but little is known about the effects of sex hormones on liver cancer development or outcome. The authors investigated whether menopause hormone therapy (MHT) affects risk, age at onset, or outcome of HCC. METHODS: We performed a case-control study of 234 female patients treated for HCC at a tertiary medical center and with 282 healthy women (controls) from January 1, 2004 through May 31, 2015. We collected detailed information on environmental exposures, ages of menarche and menopause, hysterectomies, and uses of birth control and MHT. We performed multivariable logistic and Cox regression analyses to determine the independent effects of factors associated with women on risk and clinical outcome in HCC. The primary outcomes were effect of MHT on HCC risk, the relationship between MHT with hepatitis virus infection on HCC development, and effect of MHT on age at HCC onset or survival after diagnosis of HCC. RESULTS: The estimated adjusted odds ratio (AOR) for HCC in women who ever used estrogen was 0.53 (95% confidence interval [CI], 0.32-0.88). This association was supported by the older age of HCC onset among estrogen users (mean, 64.5 ± 0.9 years) vs nonusers (mean 59.2 ± 1.1 years; P = .001) and the reduced risk of HCC among long-term users (more than 5 years) (AOR, 0.36; 95% CI, 0.20-0.63). Users of estrogen also had a reduced risk for hepatitis-associated HCC: AOR for users, 4.37 (95% CI, 1.67-11.44) vs AOR for nonusers, 17.60 (95% CI, 3.88-79.83). Estrogen use reduced risk of death from HCC (hazard ratio, 0.55; 95% CI, 0.40-0.77; P = .01). Median overall survival times were 33.5 months for estrogen users (95% CI, 25.7-41.3 months) and 24.1 months for nonusers (95% CI, 19.02-29.30 months; P = .008). CONCLUSION: In a case-control study of women with HCC vs female control subjects at a single center, we associated use of estrogen MHT with reduced risk of HCC and increased overall survival times of patients with HCC. Further studies are needed to determine the benefits of estrogen therapy for women and patients with HCC, and effects of tumor expression of estrogen receptor.
BACKGROUND & AIMS: Environmental factors have been identified that affect risk of hepatocellular carcinoma (HCC), but little is known about the effects of sex hormones on liver cancer development or outcome. The authors investigated whether menopause hormone therapy (MHT) affects risk, age at onset, or outcome of HCC. METHODS: We performed a case-control study of 234 female patients treated for HCC at a tertiary medical center and with 282 healthy women (controls) from January 1, 2004 through May 31, 2015. We collected detailed information on environmental exposures, ages of menarche and menopause, hysterectomies, and uses of birth control and MHT. We performed multivariable logistic and Cox regression analyses to determine the independent effects of factors associated with women on risk and clinical outcome in HCC. The primary outcomes were effect of MHT on HCC risk, the relationship between MHT with hepatitis virus infection on HCC development, and effect of MHT on age at HCC onset or survival after diagnosis of HCC. RESULTS: The estimated adjusted odds ratio (AOR) for HCC in women who ever used estrogen was 0.53 (95% confidence interval [CI], 0.32-0.88). This association was supported by the older age of HCC onset among estrogen users (mean, 64.5 ± 0.9 years) vs nonusers (mean 59.2 ± 1.1 years; P = .001) and the reduced risk of HCC among long-term users (more than 5 years) (AOR, 0.36; 95% CI, 0.20-0.63). Users of estrogen also had a reduced risk for hepatitis-associated HCC: AOR for users, 4.37 (95% CI, 1.67-11.44) vs AOR for nonusers, 17.60 (95% CI, 3.88-79.83). Estrogen use reduced risk of death from HCC (hazard ratio, 0.55; 95% CI, 0.40-0.77; P = .01). Median overall survival times were 33.5 months for estrogen users (95% CI, 25.7-41.3 months) and 24.1 months for nonusers (95% CI, 19.02-29.30 months; P = .008). CONCLUSION: In a case-control study of women with HCC vs female control subjects at a single center, we associated use of estrogen MHT with reduced risk of HCC and increased overall survival times of patients with HCC. Further studies are needed to determine the benefits of estrogen therapy for women and patients with HCC, and effects of tumor expression of estrogen receptor.
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