Colorectal Cancer Risk, Chronic Illnesses, Operations, and Medications: Case Control Results from the Melbourne Colorectal Cancer Study1

The associations between colorectal cancer risk and several chronic illnesses, operations, and various medications were examined in 715 colorectal cancer cases and 727 age/sex-matched controls in data derived from a large, comprehensive, population-based study of this cancer conducted in Melbourne, Australia. There was a statistically significant deficit among cases of hypertension, heart disease, stroke, chronic chest disease, and chronic arthritis and a statistically significant excess of "hemorrhoids" among cases, and all of these differences were consistent for both colon and rectal cancer and for both males and females. Although no statistically significant differences were found for other cancers, there were twice as many breast cancers among cases (16) than among controls (8) and also there were 9 uterine cancers among cases and only 2 among controls. There was a statistically significant deficit among cases in the use of aspirin-containing medication and vitamin supplements, and this was consistent for both colon and rectal cancer and for both males and females. There was a statistically significant excess of large bowel polypectomy among cases. The modeling of these significant associations simultaneously in a logistic regression equation indicated that hyperten sion, heart disease, chronic arthritis, and aspirin use were each independ ent effects and consistent for both colon and rectal cancer for both males and females and also that these effects were independent of dietary risk factors previously described in the Melbourne study. The possible rele vance of these findings towards an understanding of colorectal cancer risk and etiology is discussed. INTRODUCTION This paper describes the associations found between colorec tal cancer risk and several chronic illnesses, operations, and medications. The data are drawn from the case-control substudy arm of a large, comprehensive, population-based clinicopathological and epidemiolÃ3gica! investigation of colorectal cancer, The Melbourne Colorectal Cancer Study ( 1). The objectives for obtaining these data on illnesses, operations, and medications were partly to examine some current hypotheses of colorectal cancer risk, partly to examine previously described associations between colorectal cancer and other cancers and partly as an exploratory step to stimulate the creation of new hypotheses of colorectal cancer etiology. PATIENTS AND METHODS Definition of Cases and Controls. All histologically confirmed new cases of colorectal adenocarcinoma diagnosed in the 12-month period April 1980 to April 1981 who were usual residents of Metropolitan Melbourne (population, 2.81 million) constituted the cases (1-3). Those with a past history of ulcerative colitis or familial polyposis coli (10 cases) were excluded. Community controls, who were age/sex frequency matched with the cases, were randomly selected from the same geo graphic area from which the cases were chosen, according to a clustersampling plan devised by the Australian Bureau of Statistics (1, 2). Received 5/4/87; revised 10/15/87, 4/11/88; accepted 4/27/88. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 1This part of the Melbourne Colorectal Cancer Study was generously sup ported by the "Nicholas and Elizabeth Slezak Cancer Research Fund" of the University of Melbourne. 2To whom requests for reprints should be addressed. There were 715 cases and 727 age/sex frequency-matched controls available for this analysis. Data Collection. Data were collected by two questionnaires, which were administered by personal interview, each on a separate occasion and by two different sets of interviewers. The first questionnaire in cluded data on age, sex, country of birth, and religion; current and past illnesses, operations, and medications; bowel habit; biopsychosocial factors; number of children; and family history data. The second inter view was the dietary questionnaire, which included alcohol intake and tobacco use. The section of the interview which dealt with previous illnesses operations and medications was introduced uniformly by the interviewer as follows: "I'd like to talk to you about your general health. I am now going to read through a list of operations, illnesses, and medications. Would you tell me if you have had any of these, and if so, when?" The responses were recorded as "yes," "no," or "don't know." For operations, the actual year of the procedure was recorded. For the illnesses, the year of commencement and the year of termination of the illness was recorded. For medications, the frequency was recorded as "daily," "weekly," or "don't know" and the duration was recorded from commencement year to termination year of medication. The data obtained were not verified by any other means, such as by checking physician or hospital records or by interviewing close relatives or friends. The chronic illnesses which were asked are listed in Table 1, the cancers (other than colorectal cancer) in Table 2, the medications in Table 3, and the operations in Table 4. Data Analysis. Data manipulations and cross-tabulations were made using SPSS-x (4). The analysis of the associations between the various illnesses, operations, and medications and colorectal cancer was done using the GLIM statistical package (5) to carry out unconditional logistic regression (6), which gives multiplicative models for the KK of being a case. Design constraints, namely age and sex (due to fre quency matching between cases and controls), were adjusted for in all logistic regression models. Preliminary assessment of these associations was done univariately for colon and rectal cancers as well as for colorectal cancer (colon and rectum combined). Possible sex differences were also tested for. Simul taneous assessment of significant variables was then done and a muli ivariate model was developed and tested for consistency across site and sex and also with simultaneous adjustment for a dietary model of risk previously developed for this data set (7). RESULTS This analysis is of 715 cases (388 males and 327 females) and 727 controls (398 males and 329 females). There were 392 colon cancers and 323 rectal cancers among the cases. Cases and controls were group matched for age and sex, and the age and sex distribution of the cases and controls was therefore similar, with a mean age of 65 years (standard deviation of 10 for males and 12 for females). Univariate Analyses of Associations Illnesses. Table 1 summarizes the chronic illnesses findings. There was a statistically significant deficit among cases of hypertension, stroke, heart disease, chronic chest disease, and chronic arthritis, and these deficits were consistent in both colon and rectal cancer and in both males and females. Among cases, there was a statistically significant excess of "hemor' The abbreviation used is: RR, relative risk. 4399 Research. on October 17, 2017. © 1988 American Association for Cancer cancerres.aacrjournals.org Downloaded from COLORECTAL CANCER RISK Table I Distribution of chronic illnesses among cases and controls and relative risk estimates Males (cases, n = 388; controls, n = 398)IllnessHypertensionStrokeHeart