Menopausal hormone therapy and risk of gastrointestinal cancer: nested case–control study within a prospective cohort, and meta-analysis Jane Green 1 , Gabriela Czanner 1,2 , Gillian Reeves 1 , Joanna Watson 1 , Lesley Wise 3,4 , Andrew Roddam 1,5 and Valerie Beral 1 1 Cancer Epidemiology Unit, University of Oxford, Oxford OX3 7LF, United Kingdom 2 Department of Statistics, University of Warwick, Coventry CV4 7A, United Kingdom 3 Medicines and Healthcare products Regulatory Agency, London SW1W 9SZ, United Kingdom 4 Takeda Global Research and Development Centre (Europe) Ltd, London WC2B 4AE, United Kingdom 5 Center for Observational Research, Amgen Ltd, Uxbridge, UB8 1DH, United Kingdom Use of menopausal hormone therapy (HT) has been associated with reduced risk of colorectal cancer; evidence for its effect on other gastrointestinal cancers is limited. We conducted a nested case–control study within a UK cohort, and meta-analyses combining our results with those from published studies. Our study included women aged 501 in the UK General Practice Research Database (GPRD): 1,054 with oesophageal, 750 with gastric and 4,708 with colorectal cancer, and 5 age- and practice-matched controls per case. Relative risks (RRs) and 95% confidence intervals (CIs) for cancer in relation to prospectively-recorded HT prescriptions were estimated by conditional logistic regression. Women prescribed HT had a reduced risk of oesophageal cancer (adjusted RR for 11 vs. no HT prescriptions, 0.68, 95% CI 0.53–0.88; p 5 0.004), gastric cancer (0.75, 0.54–1.05; p 5 0.1) and colorectal cancer (0.81, 0.73–0.90; p < 0.001). There were no significant differences in cancer risk by HT type, estimated duration of HT use or between past and current users. In meta-analyses, risks for ever vs. never use of HT were significantly reduced for all three cancers (summary RR for oesophageal cancer, 0.68, 0.55–0.84, p < 0.001; for gastric cancer, 0.78, 0.65–0.94, p 5 0.008; for colorectal cancer, 0.84, 0.81–0.88, p < 0.001). In high-income countries, estimated incidence over 5 years of these three cancers combined in women aged 50–64 was 2.9/1,000 in HT users and 3.6/1,000 in never users. The absolute reduction in risk of these cancers in HT users is small compared to the HT- associated increased risk of breast cancer. Although the use of certain types of hormone therapy (HT) for the menopause has been associated with increased risk of cancers of the reproductive tract, including breast, ovary and endometrium, 1,2 there is also evidence for a reduced risk of colorectal cancer in HT users. 3–7 However it is unclear whether the association with colorectal cancer differs by HT type or pattern of use, or by cancer site. 8–10 Epidemiological evidence for an association between HT use and risk of the less common cancers of the gastrointestinal tract is limited, with most published results showing non-significant reduc- tions in risk in HT users both for oesophageal cancer 11–14 and for gastric cancer. 12,13,15–17 We report here on the relation between prospectively recorded prescribing information for HT and the subsequent incidence of cancers of the oesophagus, stomach and colorec- tum in the UK General Practice Research Database (GPRD) cohort. We also report the results of meta-analyses combin- ing our findings with other published data on the relation between HT use and the risk of each of the three gastrointes- tinal cancers. Material and Methods The general practice research database The General Practice Research Database (GPRD) is a compu- terised database containing linked anonymised patient records for about 10 million people in the UK registered with a National Health Service (NHS) primary care physician (General Practitioner, or GP); http://www.gprd.com (accessed July 13, 2010). All GP consultations, prescriptions issued by the GP, test results and diagnoses from primary and second- ary care, referrals to outpatient clinics, hospital admissions and deaths are coded by the GP and entered onto the GPRD database. For each individual, basic demographic and some lifestyle data are also recorded. GPRD prescription data have Key words: hormone therapy, cancer, colorectal cancer, oesophageal cancer, gastric cancer, menopause Grant sponsors: Medical Research Council, Independent Scientific Advisory Committee of the GPRD; Grant number: protocol number 10_006R; Grant sponsor: Cancer Research UK DOI: 10.1002/ijc.26236 History: Received 24 Jan 2011; Accepted 24 May 2011; Online 13 Jun 2011 Correspondence to: Dr. Jane Green, Cancer Epidemiology Unit, University of Oxford, Oxford OX3 7LF, United Kingdom, Tel.: þ44-1865-289-659; Fax: þ[44-1865-289-610], E-mail: jane. green@ceu.ox.ac.uk Epidemiology Int. J. Cancer: 130, 2387–2396 (2012) V C 2011 UICC International Journal of Cancer IJC