Menopause and colorectal cancer

Post-menopausal women who have never used hormone replacement therapy have a higher risk of colon, but not rectal, cancer than do premenopausal women of the same age, socio-cultural class and dietary habits. Such risk increase seems to last about 10 years and to be restricted to lean women, a group who have lower levels of oestradiol after ovarian function ceases after menopause. © 2000 Cancer Research Campaign


SUBJECTS AND METHODS
The data were derived from two case-control studies on colorectal cancer: the first conducted between 1985 and 1991 in the greater Milan area (Negri et al, 1989) and the province of Pordenone, in Northeast Italy ; and the second conducted between 1992 and 1996 in the provinces of Pordenone and Gorizia in Northeast Italy; the urban areas of Milan and Genoa and the province of Forlì in northern Italy; Latina in central Italy; and the urban area of Naples in southern Italy . Centrally trained interviewers identified and questioned cases of colorectal cancer and controls during their hospital stay.
Cases included 1536 women below age 75 years with histologically confirmed cancer (i.e. diagnosed within the year before interview) of the colon (994 cases, median age 61) and rectum (542 cases, median age 62), admitted to the major teaching and general hospitals in the areas under surveillance.
The control group included 3110 women younger than 75 years (median age of 57), residing in the same geographical areas and admitted for a wide spectrum of acute, non-neoplastic, non-digestive tract, non-hormone-related disorders to the same network of hospitals from which cases were recruited. Of these, 43% were admitted for traumas, 14% had non-traumatic orthopaedic disorders, 13% had acute surgical conditions, 6% had eye conditions and 24% had other miscellaneous diseases, such as ear, nose and throat, skin, or dental disorders. Cases and controls had the same referral pattern. Fewer than 5% of cancer cases and control subjects refused to be interviewed.
Structured questionnaires were used to collect information on sociodemographic factors, personal characteristics and habits (such as smoking, alcohol and coffee consumption), frequency of consumption of selected foods and a problem-oriented medical history. Information was also collected on menstrual and reproductive factors and on the use of oral contraceptives and HRT (Fernandez et al, 1998). Women were considered post-menopausal if they reported no menstrual periods in the 12 months prior to colorectal cancer diagnosis or hospital admission (controls), or had undergone hysterectomy and/or bilateral oophorectomy.
To examine the effect of menopause on colorectal cancer risk independently of the effect of HRT, most analyses were restricted to women who had never used HRT. Odds ratios (ORs), together with the corresponding 95% CIs, were derived from unconditional multiple logistic regression equations, fitted by the method of maximum likelihood (Breslow and Day, 1980). Terms included in the regression equations were age (in quinquennia plus a continuous term), centre, study period, education, parity, vegetable intake and body mass index (BMI, kg m -2 ). Allowance for other potentially confounding variables (smoking habit, alcohol drinking, coffee intake, meal frequency, family history of colorectal cancer and, for the more recent study, physical activity, total energy intake and aspirin use) did not substantially modify any of the ORs in Tables 1 and 2 Table 1 shows the distribution of cases of cancer of the colon and rectum and control subjects according to menopause-related variables. Compared to premenopausal, post-menopausal women who had never used HRT were at 1.5-fold increased risk (95% CI 1.1-2.0) of colon cancer. Conversely, women who had ever taken HRT had an OR of 0.9 (95% CI 0.6-1.4). Type of menopause did not seem to modify colon cancer risk. Women who reported menopause at age 50-52 years had an OR of 1.5 (95% CI 1.1-1.9) compared to those whose menopause was at age 44 or less, but the trend in risk was not linear. Women whose menopause occurred 1-9 years before diagnosis had a substantially higher risk (OR = 1.7, 95% CI 1.2-2.3) than premenopausal ones. Thereafter, ORs declined progressively with time since menopause. Trend by years since menopause among post-menopausal women was significant (Table 1). For rectal cancer, no significant associations with age at menopause or years since menopause were found. Ever users of HRT showed decreased risk of rectal cancer compared to premenopausal women (Table 1).

RESULTS
The relation of colon cancer risk with time since menopause differed significantly according to BMI tertile ( Table 2). The risk elevation in the 10 years subsequent to menopause seemed restricted to women with BMI below 23 (OR = 2.2; 95% CI 1.3-3.7) (χ 2 1 for trend = 6.00, P = 0.02). Conversely, the decline in risk by years since menopause was not significant in women whose BMI was between 23 and 26 (χ 2 1 for trend = 1.37, P = 0.24) and was absent among those with BMI higher than 26 (χ 2 1 for trend = 0.16, P = 0.69). Trends by age at and years since menopause did not differ between women with natural and those with surgical menopause. Table 1 Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) a of cancer of the colon and rectum according to menopausal status, type of and age at menopause, and years since menopause. Italy, 1985Italy, -1996