Objective-To examine the relation between the use of aspirin and non-steroidal anti-inflammatory drugs and the presence of asymptomatic colorectal adenomas.Design-Case-control study of subjects participating in a randomised controlled trial of faecal occult blood screening for colorectal cancer. Data on analgesics and other drugs were obtained from a questionnaire which was mainly concerned with diet and was administered by an interviewer.Setting-Nottingham. Subjects-147 patients with positive results in faecal occult blood tests who were found to have colorectal adenomas (cases), 153 age and sex matched control subjects with negative results in such tests (negative controls), and 176 control subjects with positive results in the tests who were found not to have colorectal adenomas (positive controls).Main outcome measures-Relative risk of developing colorectal adenomas according to frequency and duration ofuse ofanalgesics.Results-Cases reported taking less aspirin and non-steroidal anti-inflammatory drugs than the negative controls, with the estimated relative risk for any use being 0 49 (95% confidence interval 0 3 to 0.8). The inverse association was less strong when cases were compared with the positive controls (0-66 (0 4 to 1.1)). The association was specific for aspirin and non-steroidal anti-inflammatory drugs there being no association with paracetamol or other drugs. Prescribed use of non-steroidal antiinflammatory drugs for longer than five years was associated with the lowest risk (0.21 (0.1 to 0 8)), although the numbers reporting prolonged prescribed use were small.Conclusions-These findings support the hypothesis that aspirin and non-steroidal antiinflammatory drug use protects against the development ofcolorectal neoplasia.

Summary Diets high in animal fat and protein and low in fibre and calcium are thought to be factors in the etiology of colorectal cancer. Intakes of these nutrients were determined in three groups participating in a randomised trial of faecal occult blood (FOB) screening. A diet history was obtained by interview from 147 patients with colorectal adenomas, 153 age and sex matched FOB-negative controls (a) and 176 FOB-positive controls without colorectal neoplasia (b). Unconditional logistic regression was used to estimate relative risks (RR) and 95% confidence limits (t) adjusted for age, sex and social class.After adjustment for total energy intake, no associations were found with total, saturated or monounsaturated fat, or calcium intake. For total fibre intake there were non-linear relationships with both control groups with the crude RR for highest quintiles of total fibre intake compared to the lowest being 0.6, although this pattern was no longer apparent after adjustment for energy intake with group (a). In comparison with group (b) cereal fibre intake showed a more consistent inverse relationship with adenoma prevalence with the RR for ascending quintiles of intake being 1.0, 0.7 (0.3-1.6), 0.5 (0.3-1.1), 0.7 (0.4-1.4) and 0.3 (0.1-0.6) (trend x2 = 8.80, p = 0.003). In comparison with group (a), the adjusted RR for the highest quintile of cereal fibre intake compared with the lowest was 0.6, but no clear trend was apparent. There was an unexpected positive relationship between adenomas and polyunsaturated fat intake with the RR for having an adenoma being 1.0, 2.8 (1.3-6.1), 1.6 (0.7-3.4), 3.5 (1.6-7.5) and 2.3 (1.1-5.0) for ascending quintiles of polyunsaturated fat intakes (trend x2 = 4.8, P = 0.03) in comparison with group (a) only.Our data, while providing no support for the role of dietary animal fat or protein, do support the protective role of dietary cereal fibre in the etiology of colorectal adenomas.High intakes of animal fat and protein (Wynder & Shigematsu, 1967;Drasar and Irving, 1973), and low intakes of fibre (Burkitt, 1971) and calcium (Newmark et al., 1984) have been postulated to increase the risk of colorectal cancer. However, the role of these nutrients has not been clarified in analytical epidemiological studies (Zaridze, 1983;Willett, 1989a (Paul & Southgate, 1978).In addition to the nutrients about which we had specific hypotheses, we considered total energy intake as an important potential confounder (Willett, 1989b, pp , the sources of protein and fibre, and the different types of fatty acid.We also asked subjects about the frequency of consumption of certain foods which might be markers of 'healthy Correspondence: J. Little,

(Bartram & Wynder, 1989), and obesity appears at most to be weakly related to colorectal cancer (Willett, 1989a). Interpretation of the weak association with obesity is complicated by the fact that weight loss may be a sign of the disease. To obviate the possible direct effect of the tumour on a variety of possible risk factors, studies of adenomatous polyps have been advocated. Physical activity has been considered only in two previous studies, in one of which no association was found (Stemmermann et al., 1988) and in the other an inverse association (Kono et al., 1991). The studies of the relationship between adenomas and energy intake (Hoff et al., 1986;Macquart-Moulin et al., 1987;Stemmermann et al., 1988) and body size (Mannes et al., 1986;Sandler et al., 1988;Stemmermann et al., 1988;Kono et al., 1991) (Little et al., 1993).During the interview, a complete occupational history was recorded. This information was classified according to the Registrar General's classification of occupations (Office of Population Censuses and Surveys, 1970). These data were used to derive measures of socio-economic status based on the subject's current job at interview, their last job before retirement, the job they held for the longest period (if this was 'housewife' or 'househusband', that held for the second longest period was considered) and the job of the highest class.Subjects were asked to state, for the year prior to interview, how much of the day they spent sitting, standing, walking or in heavy work (with categories none, less than half, about half or more and practically all) and how often in this period they took the following forms of exercise -sport/ keep-fit, hard labour such as heavy gardening, housework, brisk walking for half an hour continuously, running or cycling for half an hour continuously and other exercise (with the categories of none, less than once a week, once a week, twice a week or more).Repeatability Thirty-four repeat interviews were completed. The correlation coefficient for energy intake between the two interviews was 0.57. Regarding physical activity, the agreement was better for variables relating to the frequency of undertaking different specific activities (kappa 0.64-0.76) than for the proportion of the day spent in different activities (kappa 0.34-0.48 The method of calculating energy intake has been described in the accompanying paper (Little et al., 1993). In addition to considering associations with each specific component of physical activity in the year prior to interview, summary scores were also derived. Scores for daily activity level in the year prior to interview were calculated as the product of a value for the proportion of the day spent on the activity times the intensity of the activity. The values for the proportion of the day spent on the activity were taken as 1 for less than half, 2 for about half or more and 3 for

The study does not support an association between colorectal cancer and fecal bile acids or pH. However, there is evidence that increases in major bile acids are associated with villous adenomas.