Research Papers: Gastrointestinal CancerReproductive factors and risk of esophageal squamous cell carcinoma in northern Iran: a case–control study in a high-risk area and literature reviewIslami, Farhada,b; Cao, Yinb,c; Kamangar, Farind; Nasrollahzadeh, Dariushf,a; Marjani, Haji-Amini,a; Shakeri, Ramina; Fahimi, Samang; Sotoudeh, Masouda; Dawsey, Sanford M.e; Abnet, Christian C.e; Boffetta, Paolob,h; Malekzadeh, RezaaAuthor Information aDigestive Disease Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran bThe Tisch Cancer Institute and Institute for Transitional Epidemiology, Mount Sinai School of Medicine, New York, New York cDepartment of Epidemiology, Harvard School of Public Health, Boston, Massachusetts dDepartment of Public Health Analysis, School of Community Health and Policy, Morgan State University, Baltimore eDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA fDepartment of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden gDepartment of Public Health and Primary Care, University of Cambridge, Cambridge, UK hInternational Prevention Research Institute, Lyon, France iResearch Center for Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran All supplementary digital content is available directly from the corresponding author. Correspondence to Farhad Islami, MD, PhD, The Tisch Cancer Institute and Institute for Transitional Epidemiology, The Mount Sinai School of Medicine, One Gustave L. Levy Place, P.O. Box 1057, New York, 10029 NY, USA Tel: +1 212 659 5556; fax: +1 212 996 0407; e-mail: email@example.com Received October 25, 2012 Accepted October 31, 2012 European Journal of Cancer Prevention: September 2013 - Volume 22 - Issue 5 - p 461-466 doi: 10.1097/CEJ.0b013e32835c7f87 Buy Metrics Abstract Several epidemiologic studies have suggested an inverse association between female reproductive factors and the risk of esophageal squamous cell carcinoma (ESCC), but the evidence is not conclusive. We examined the association of the number of pregnancies, live births, and miscarriages/stillbirths in women and the association of the number of children in both sexes with the risk of ESCC in Golestan Province, a high-risk area in Iran. Data from 297 histopathologically confirmed ESCC cases (149 women) and 568 controls (290 women) individually matched to cases for age, sex, and neighborhood of residence were included in this analysis. Conditional logistic regression was used to calculate odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). The average numbers of live births and miscarriages/stillbirths among the controls were 8.2 and 0.8, respectively. Women with six or more live births were at ∼1/3 the risk of ESCC as those with 0–3 live births; the OR (95% CI) for having 6–7 live births was 0.33 (0.12–0.92). In contrast, the number of miscarriages/stillbirths was associated with an increase in the risk of ESCC. The OR (95% CI) for at least three versus no miscarriages/stillbirths was 4.43 (2.11–9.33). The number of children in women was suggestive of an inverse association with ESCC, but this association was not statistically significant; in men, no association was observed. The findings of this study support a protective influence of female hormonal factors on the risk of ESCC. However, further epidemiological and mechanistic studies are required to prove a protective association. © 2013 Lippincott Williams & Wilkins, Inc.