Colorectal cancer is the third most frequent cancer and the second cause of cancer mortality in women in the Western World. Although the mechanism has not been confirmed, epidemiological studies and some evidence from animal studies suggest that reproductive hormones, specifically estrogens, may protect against the development of colon cancer in post-menopausal women. This historical population-based nested case-control study will investigate the effect of past exposure to hormonal replacement therapy (HRT) on the risk of developing colon cancer. Methods: The source population for the study will be the dynamic cohort defined by membership in the Saskatchewan Prescription Drug Plan (SPDP). Incident cases of colon cancer over 50 years of age will be accrued by the provincial cancer registry from 1981 to 98 (n=2,400). Four age-matched controls per case will be selected from the source population, using incidence density sampling. Detailed prescription drug exposure data on HRT over a minimum of 5 years before diagnosis and up to a maximum 20 years will be obtained from the SPDP. Also obtained from the SPDP for this same time period will be prescription information on oral contraceptives and NSAIDs. Data on potential confounders will be obtained from a sample of the subjects accrued from January 1, 1994 to December 31, 1998 by means of telephone interviews carried out blind to disease status. The sampling fractions will vary according to disease and drug exposure status, so that the second stage sample will contain about 150 exposed cases and controls and 150 unexposed cases and controls (total=500-650 subjects). Confounding will be controlled and effect modification will be studied with logistic regression, using appropriate correction for the second stage-sampling scheme. Significance: The applicant is in a unique position to examine the respective effect of dose, duration and timing of HRT exposure on the risk of developing colon cancer, for a period of time as far back as 20 years prior to the index data. The findings will elaborate on the risk/benefit profile of HRT, which will assist women and their physicians to make informed decisions. In addition the results will be of value in the development of comprehensive practice guidelines for HRT.
| Hanley, James A; Csizmadi, Ilona; Collet, Jean-Paul (2005) Two-stage case-control studies: precision of parameter estimates and considerations in selecting sample size. Am J Epidemiol 162:1225-34 |
| Csizmadi, Ilona; Collet, Jean-Paul; Boivin, Jean-Francois et al. (2004) Health-related behavior and the use of hormone replacement therapy. Pharmacoepidemiol Drug Saf 13:65-71 |
| Csizmadi, Ilona; Collet, Jean-Paul; Benedetti, Andrea et al. (2004) Defining hormone replacement therapy in longitudinal studies: impact on measures of effect. Pharmacoepidemiol Drug Saf 13:215-25 |
| Csizmadi, I; Collet, J-P; Benedetti, A et al. (2004) The effects of transdermal and oral oestrogen replacement therapy on colorectal cancer risk in postmenopausal women. Br J Cancer 90:76-81 |
| Csizmadi, Ilona; Benedetti, Andrea; Boivin, Jean-Francois et al. (2002) Use of postmenopausal estrogen replacement therapy from 1981 to 1997. CMAJ 166:187-8 |
