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Title: Reproductive factors and breast cancer and colorectal cancer incidence and mortality among postmenopausal women in the European Prospective Investigation into Cancer and Nutrition (EPIC)
Author: Kadi, Mai
ISNI:       0000 0004 6420 9153
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2014
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Cancers of the breast and colorectum are two of the most frequently diagnosed malignancies worldwide and despite improvements in treatment and survival, are leading causes of death. Reproductive factors, such as age at menarche, childbirth and age at menopause have been consistently linked to risk of developing breast cancer while exposure to exogenous hormones through use of oral contraceptives (OC) and hormone therapy (HT), are associated with increased risk of breast cancer but a reduced risk of colorectal cancer. These observations support the hypothesis that variation in endogenous hormone pathways contribute to breast and colorectal cancer development. However, while a substantial body of literature has established the significance of reproductive factors and exogenous hormone use in the initiation of these tumours, data on their association with mortality among breast and colorectal cancer patients are limited. To further knowledge on the role of reproductive factors and exogenous hormone use on the natural history of breast and colorectal cancer, a comprehensive assessment of these factors in relation to breast and colorectal cancer development as well as survival was undertaken among participants of the European Prospective Investigation into Cancer (EPIC). Specifically, among 150,251 women defined as postmenopausal at study baseline, the association of age at first and last menstruation, history of pregnancy, number of full-term pregnancies, the age at birth of the first and last child, breast feeding, accumulative breast feeding duration, and ever use of oral contraceptives and hormone therapy was investigated in relation to (i) breast cancer incidence, (ii) all-cause and breast cancer-specific mortality amongst breast cancer patients, (iii) colorectal cancer incidence and (iv) all-cause and colorectal cancer-specific mortality among colorectal cancer patients. Statistical analyses were conducted using Cox proportional hazards modelling with adjustment for established breast and colorectal cancer risk factors. In multivariable analyses, a later age at menarche was associated with associated with 11% reduced risk of breast cancer ( hazard ratio [HR] ≥15 vs 12 years = 0.89, 95% confidence intervals [CI]= 0.80-1.00; P-trend=0.0001); older age at menopause was found to be associated with increased risk of breast cancer (>55 vs ≤50 HR=1.27, 95% CI=1.10-1.47; P-trend < 0.0001); further giving birth to at least one child significantly reduced the risk of developing breast cancer by 16% (HR=0.84, 95% CI= 0.77-0.91) and reduced the risk of all-cause and breast cancer-specific death among breast cancer patients by 37% (HR=0•63, 95%CI: 0.46-0.86) and 45% (HR= 0.55, 95% CI= 0.37-0.82) respectively, compared to nulliparous women. Women with >4 children were at 26% reduced risk of breast cancer expressing oestrogen receptors (ER) compared to women who had one child (HR=0.74, 95%CI: 0.64-0.86; P-trend=0.002). Breast cancer patients who expressed the ER and had at least one pregnancy were at 57% reduced risk of death compared to nulliparous patients who expressed ER (HR= 0.43, 95%CI: 0.26-0.71). The use of exogenous hormones in the form of oral contraceptives and postmenopausal hormones was found to reduce the risk of developing colorectal cancer in postmenopausal women by 15% (OC users vs non-users HR= 0.85, 95%CI: 0.76-0.95) and 14% (HT users vs non-users HR= 0.86, 95% CI= 0.0.79-0.96). However, it seems that hormone therapy users have 28% higher risk of fatal colorectal cancer compared to non-users (HR=1.28, 95%CI: 1.01-1.61). The results of this large-scale prospective investigation indicate that reproductive factors and use of exogenous hormones influence the development of breast and colorectal cancer and may also be associated with survival among patients with these malignancies. If confirmed in other studies, these findings may be further explored in prognostic modelling and may help inform treatment and surveillance of high-risk groups.
Supervisor: Riboli, Elio ; Wark, Petra ; Gunter, Marc Sponsor: Saudi Cultural Bureau
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral