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Open Access Highly Accessed Research article

Associations of hormone replacement therapy and oral contraceptives with risk of colorectal cancer defined by clinicopathological factors, beta-catenin alterations, expression of cyclin D1, p53, and microsatellite-instability

Jenny Brändstedt12*, Sakarias Wangefjord12, Björn Nodin1, Jakob Eberhard1, Karin Jirström1 and Jonas Manjer234

Author Affiliations

1 Department of Clinical Sciences, Lund, Oncology and Pathology, Lund University, Skåne University Hospital, Lund, Sweden

2 Department of Surgery, Skåne University Hospital, Malmö, Sweden

3 Department of Clinical Sciences, Malmö, Lund University, Skåne University Hospital, Malmö, Sweden

4 Department of Plastic Surgery, Skåne University Hospital, Malmö, Sweden

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BMC Cancer 2014, 14:371  doi:10.1186/1471-2407-14-371

Published: 25 May 2014

Abstract

Background

Postmenopausal hormone therapy (HRT) and oral contraceptive (OC) use have in several studies been reported to be associated with a decreased colorectal cancer (CRC) risk. However, data on the association between HRT and OC and risk of different clinicopathological and molecular subsets of CRC are lacking. The aim of this molecular pathological epidemiology study was therefore to evaluate the associations between HRT and OC use and risk of specific CRC subgroups, overall and by tumour site.

Method

In the population-based prospective cohort study Mamö Diet and Cancer, including 17035 women, 304 cases of CRC were diagnosed up until 31 December 2008. Immunohistochemical expression of beta-catenin, cyclin D1, p53 and MSI-screening status had previously been assessed in tissue microarrays with tumours from 280 cases. HRT was assessed as current use of combined HRT (CHRT) or unopposed oestrogen (ERT), and analysed among 12583 peri-and postmenopausal women. OC use was assessed as ever vs never use among all women in the cohort. A multivariate Cox regression model was applied to determine hazard ratios for risk of CRC, overall and according to molecular subgroups, in relation to HRT and OC use.

Results

There was no significantly reduced risk of CRC by CHRT or ERT use, however a reduced risk of T-stage 1–2 tumours was seen among CHRT users (HR: 0.24; 95% CI: 0.09-0.77).

Analysis stratified by tumour location revealed a reduced overall risk of rectal, but not colon, cancer among CHRT and ERT users, including T stage 1–2, lymph node negative, distant metastasis-free, cyclin D1 - and p53 negative tumours.

In unadjusted analysis, OC use was significantly associated with a reduced overall risk of CRC (HR: 0.56; 95% CI: 0.44-0.71), but this significance was not retained in adjusted analysis (HR: 1.05: 95% CI: 0.80-1.37). A similar risk reduction was seen for the majority of clinicopathological and molecular subgroups.

Conclusion

Our findings provide information on the relationship between use of HRT and OC and risk of clinicopathological and molecular subsets of CRC.