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R M Bostick

Publications and source records attributed to R M Bostick.

At least 37 records · Page 2Linked to original sources
PubMed1996

Quantification of proliferating cell nuclear antigen in large intestinal crypt by computer-assisted image analysis.

Measurements of proliferating cell nuclear antigen (PCNA) labeling of the large intestinal crypts scored by experienced observers were compared with those generated by computer-assisted image analysis (CAIA). (CAIA was performed at Pathology Expertise, Inc., Newton, MA, by A. V. Sotnikov.) Serial sections (3 microns) of the rectal biopsy specimens from 32 patients were immunostained for PCNA and then counterstained with hematoxylin. The same set of slides and rules for the location/acquisition of complete crypts was used to assess a minimum of ten complete crypts/patient. Each crypt was subdivided longitudinally into five equal compartments. With CAIA, the images were stored digitally, and once the color references were set, the areas occupied by labeled and counterstained nuclei were quantified automatically. The labeling index (LI) was calculated from the PCNA-labeled nuclei area/total nuclei area in CAIA and from the number of labeled cells/total number of cells in visual scoring. The LI of whole crypts averaged 1.04 +/- 0.18 by CAIA and 3.91 +/- 0.46 by the visual method, and the Spearman correlation (rs) between the two methods was 0.89. The different modes of evaluation and color reference selection are likely to have contributed to the differences in the LI ranges observed in the two methods. The high correlation between PCNA quantification by CAIA and visual scoring by experienced technicians indicates that CAIA can reliably rank individual subjects. Thus, measurement of PCNA labeling by CAIA is a practical alternative for evaluating colorectal epithelial cell proliferation.

Adult↗
PubMed1996

Hormone replacement therapy is associated with lower risk of adenomatous polyps of the large bowel: the Minnesota Cancer Prevention Research Unit Case-Control Study.

Evidence of a role for steroid hormones and reproduction in colon neoplasia remains tantalizing but unclear. Hormone replacement therapy (HRT) has been reported in a number of recent studies to be associated with a reduced risk of colon cancer. A case-control study was undertaken to establish whether HRT is associated with lower risk of adenomatous polyps. This case-control study was undertaken as a project of the Minnesota Cancer Prevention Research Unit. Cases (n = 219) were women, ages 30-74 years with colonoscopy-proven, pathology-confirmed, adenomatous polyps of colon and rectum recruited at Digestive Healthcare PA (Minneapolis, MN). Two control groups were selected: women without polyps at colonoscopy (n = 438) at Digestive Healthcare and age- and zip code-matched women selected from the general community (n = 247). Response rates were 68% among those colonoscoped and 65% among community controls. Parity, age at first live birth, and oral contraceptive use did not distinguish cases from either control group. Multivariate adjusted odds ratios and 95% confidence limits for use of HRT for less than 5 years (compared with never use) among postmenopausal women were 0.52 (0.32-0.85) versus colonoscopy-negative controls and 0.74 (0.44-1.26) versus community controls. For 5 years of use or greater, the corresponding figures were 0.39 (0.23-0.67) and 0.61 (0.34-1.07). These results were not materially different when stratified on body mass index, oophorectomy, hysterectomy, aspirin use, or family history. There is no marked increase in risk even 5 years after cessation of HRT use. HRT appears to lower risk of colorectal adenomatous polyps, suggesting that it acts quite early in the neoplastic process. Mechanisms remain unclear. Reduction of risk of colorectal neoplasia is an additional benefit of postmenopausal HRT.

Adenocarcinoma↗
PubMed1996

Reproducibility of the measurement of colonic proliferation using bromodeoxyuridine across laboratories.

Although measures of colonic cell proliferation are being used as potential intermediate markers in chemoprevention studies, measurement standardization is still ongoing. This study was designed to assess the reproducibility of the labeling index quantification, as measured by bromodeoxyuridine, across four laboratories experienced in its use. Each institution submitted 10 slides, with one circled area of each slide to be scored. Each site followed its standard procedures for scoring colonic crypts; no attempts to standardize these procedures were made. There was high concordance among the laboratories on whether scorable crypts were present on a particular slide, but only two pairs of laboratories demonstrated agreement statistically greater than that predicted by chance. The overall difference among the sites on the number of scorable crypts was marginally significant (P = 0.083), and there was a highly significant overall difference in the magnitude of the labeling index (P < 0.0001). Sites 1 and 2 tended to have similar results, as did sites 3 and 4, most likely due to common training. Even with these discrepancies, high correlation (r > 0.75) was observed among the reported labeling index values for each pair of laboratories. Without standardized training, these laboratories may differ in the crypts considered appropriate for counting and in whether cells are counted as labeled or unlabeled. These results suggest that standardized training in scoring across all sites performing labeling index determinations is required to assure reproducibility across sites or studies. These results may also help explain discrepancies in the average values of the labeling index reported in the literature.

Analysis of Variance↗
PubMed1995

Association of body mass index and body fat distribution with risk of lung cancer in older women.

Obesity has been associated with an increased risk of cancer at a number of sites. A notable exception appears to be lung cancer, for which several studies suggest a modest inverse association. However, cigarette smoking is directly associated with lung cancer and inversely associated with body mass index. To investigate the hypothesis that body mass index is associated with lung cancer independent of cigarette smoking, the authors analyzed data from a prospective cohort study of 41,837 Iowa women aged 55-69 years at baseline in 1986. In addition, they examined whether central adiposity (high waist/hip ratio) was associated with lung cancer incidence. Through 1992 (6 years of follow-up), 233 cases of lung cancer were identified through the State Health Registry of Iowa. The body mass index at several ages was calculated from self-reports of height at baseline and weights at ages 18, 30, 40, and 50 years and at baseline. Current and former smokers generally had lower mean body mass indices than did nonsmokers at all ages except 18 years. Cases generally had lower body mass indices than did noncases at all ages except 18 and 30 years but, among current smokers, cases had higher mean body mass indices than did noncases at all ages except baseline, although the differences were not statistically significant. An apparent positive association of a high waist/hip ratio with lung cancer in the total cohort was found to be primarily accounted for by a higher waist/hip ratio in current and former smokers. When stratified by smoking status and adjusted for other risk factors, including age and pack-years of smoking, the body mass index at baseline, body mass index at age 50 years, and waist/hip ratio were not associated with lung cancer. The results of multivariate analyses suggest that the inverse association of body mass index with lung cancer can be explained by smoking status and that the positive association of waist/hip ratio with lung cancer can be explained by pack-years of smoking.

Age Distribution↗
PubMed1995

Calcium and colorectal epithelial cell proliferation in sporadic adenoma patients: a randomized, double-blinded, placebo-controlled clinical trial.

BACKGROUND: The kinetics of colorectal epithelial cell proliferation is altered in patients at increased risk for colon cancer. Calcium administration ameliorates such proliferative changes in rodents. Findings in preliminary clinical trials have suggested similar effects in humans. PURPOSE: A randomized, double-blind, placebo-controlled, clinical trial was designed to determine whether calcium supplementation will reduce the colorectal epithelial cell proliferation rate and normalize the distribution of proliferating cells within colorectal crypts (i.e., shift the zone of proliferation from the entire crypt to the lower 60% of the crypt, which is thought to be the normal proliferative zone of the crypt) in patients with sporadic adenomas. METHODS: Sporadic adenoma patients (n = 193) were treated with placebo (n = 66), 1.0 g calcium (n = 64), or 2.0 g calcium (n = 63) daily for 6 months. Rectal mucosa biopsy specimens were obtained at base line and at 1-, 2-, and 6-month follow-up. Cell proliferation was measured by detection of S-phase-associated proliferating cell nuclear antigen by immunohistochemical methods. The cell proliferation rate, called labeling index (LI), was calculated as the proportion of labeled cells in the crypts. The deviation of the proliferative zone from the normal location in the lower 60% of the crypt was calculated as the proportion of labeled cells in the upper 40% of the crypt, called distributional index (phi h). The effects of calcium treatment on the LI and phi h were expressed as relative effects--(calcium follow-up/calcium base line)/(placebo follow-up/placebo base line). Calculations and inference testing of the relative effects were accomplished using a repeated-measures mixed model on log-transformed LI and phi h values. All statistical tests were two-sided. RESULTS: Scorable biopsy specimens were obtained on 170 patients at base line, 164 at 1 month, 161 at 2 months, and 163 at 6 months. The difference in the change in the LI between the combined calcium groups and the placebo group was insignificant, with a relative effect of calcium versus placebo of 0.97 (P = .87). However, for the phi h, the relative effect of calcium versus placebo was 0.50 (P = .05) in the combined calcium groups, 0.56 (P = .16) in the 1.0-g calcium group, and 0.44 (P = .05) in the 2.0-g calcium group. CONCLUSIONS: Calcium supplementation normalizes the distribution of proliferating cells without affecting the proliferation rate in the colorectal mucosa of sporadic adenoma patients. IMPLICATIONS: These results support further study of whether alterations in colon cell proliferative kinetics represent true intermediate steps in colon carcinogenesis that can be used to investigate the etiology and prevention of, and whether a higher calcium consumption can reduce the risk of, colon cancer.

Adult↗
PubMed1995

Dietary intake of energy and animal foods and endometrial cancer incidence. The Iowa women's health study.

To assess the relations of dietary intake of energy and animal foods to endometrial cancer risk, dietary analyses were performed using data from a prospective cohort study of over 23,000 postmenopausal Iowa women who responded to a mailed questionnaire in 1986 and were followed through the end of 1992 for cancer incidence and total mortality. Usual intakes of 127 food items were measured by a semiquantitative food frequency questionnaire. After 7 years of follow-up, 216 incident endometrial cancer cases had been ascertained. There was no statistically significant association of dietary intake of energy and most animal foods with endometrial cancer incidence over the 7-year follow-up period. Stratified analyses, however, suggested that intake of energy from plant foods may be inversely associated with endometrial cancer risk in the latter years of follow-up (trend test, p = 0.03), while high intake of energy and foods from animal sources related to slightly, but not statistically significantly, elevated risks of this cancer in the earlier years of follow-up. The only significant dose-response relation observed in food group analyses was for processed meat and fish, for which a significant 50% excess risk of endometrial cancer was found among women in the highest versus the lowest tertile of intake. This study suggests that dietary intake of energy and most animal foods is not related to or is only weakly related to the risk of endometrial cancer among postmenopausal US women.

Cohort Studies↗
PubMed1994

Familial clustering of breast and prostate cancers and risk of postmenopausal breast cancer.

BACKGROUND: Previous studies have suggested that cancers of the breast and prostate cluster in families and that the presence of both diseases in a family may be associated with increased risk of breast cancer. PURPOSE: Our purpose was to evaluate whether 1) prostate cancer aggregates in families with postmenopausal breast cancer, 2) families with cancers of the breast and prostate are the same ones as families with cancers of the breast and ovary, and 3) a family history of prostate cancer is associated with increased risk of postmenopausal breast cancer. METHODS: We analyzed data from a large prospective cohort study of Iowa women that were (at baseline) aged 55-69 years in 1986. At the third follow-up survey in 1992, self-reported data on family history of breast, ovarian, and prostate cancers in parents and siblings were provided by 30,883 women. Additional information was collected to ascertain whether the age-of-onset of breast cancer in mothers or sisters was before or after the age of 45 years. Cancer occurrence was documented using the State Health Registry of Iowa. RESULTS: History of prostate cancer in their father or a brother was reported by 3384 (11.0%) of the women, and a total of 4090 women (13.2%) reported breast cancer in their mother or a sister. A positive family history of both cancers was reported by 556 women, significantly (two-sided P < .001) greater than the 457 women expected if the family histories were independent. The aggregation of breast, prostate, and ovarian cancers was reported by 22 participants, greater than the 2.7 expected (two-sided P < .0001). During 6 years of follow-up, 578 breast cancers were identified in the cohort at risk. Compared with women without a family history of either cancer, women with a family history of breast cancer had a relative risk (RR) of 1.37 (95% confidence interval [CI] = 1.06-1.79) if the affected relative had onset after the age of 45 years, and an RR of 1.71 (95% CI = 1.13-2.61) if the affected relative had onset at or before the age of 45. A family history of prostate cancer in the absence of a family history of breast cancer was associated with an RR of 1.19 (95% CI = .90-1.56). However, a family history of both breast and prostate cancers was associated with RRs of 2.06 (95% CI = 1.23-3.45) and 2.35 (95% CI = .97-5.67) for breast cancer onset in relatives of greater than 45 and less than or equal to 45 years, respectively. CONCLUSIONS: These observations are concordant with recent reports that suggest a shared familial risk (inherited or environmental) for these hormone-dependent malignancies.

Aged↗
PubMed1994

Statistical analysis of proliferative index data in clinical trials.

Measurements of proliferative activity in colonic epithelial cells are being used as surrogate endpoints in clinical trials for colon cancer prevention. Proliferative index data exemplify an important type of clinical trial endpoint. The outcome variable is a proportion in which the denominator is an ancillary statistic and in which measurement error and technician judgement are important sources of variability. The paper proposes a statistical model for a repeated measures clinical trial with this type of endpoint, in the context of proliferative activity data. The model is a two-stage random effects linear model in the log scale. In addition to fixed effects covariates, it explicitly incorporates two major sources of variability: the number of epithelial cells counted and the reader effect. Although the resulting likelihood is complicated, one can fit an approximate likelihood with minimal loss of efficiency using standard packages. We apply the model to a pilot randomized clinical trial.

Cell Division↗
PubMed1994

Vegetables, fruit, and colon cancer in the Iowa Women's Health Study.

Previous epidemiologic studies have shown an inverse association between vegetable and fruit consumption and colon cancer risk; few of these studies have been prospective or have focused on women. This report describes results from a prospective cohort study of 41,837 women aged 55-69 years who completed a 127-item food frequency questionnaire in 1986 and were monitored for cancer incidence for 5 years via the State Health Registry of Iowa. After specific exclusion criteria were applied, 212 colon cancer cases and 167,447 person-years were available for analysis. Intakes of 15 vegetable and fruit groups and dietary fiber were the major factors of interest. Consumption of garlic was inversely associated with risk, with an age- and energy-adjusted relative risk of 0.68 (95% confidence interval (CI) 0.46-1.02) for the uppermost versus the lowermost consumption levels. Inverse associations were also observed for intakes of all vegetables and dietary fiber; age- and energy-adjusted relative risks for the uppermost versus the lowermost intake quartiles were 0.73 (95% CI 0.47-1.13) and 0.80 (95% CI 0.49-1.31), respectively. Associations for the other vegetable and fruit groups were less remarkable.

Age Factors↗
PubMed1994

Dietitian practices for adult outpatients with hypercholesterolemia referred by physicians. The Minnesota Dietitian Survey.

OBJECTIVE: To characterize the physician-to-dietitian referral process and dietitian practice patterns and opinions related to adult outpatients with hypercholesterolemia. DESIGN: Cross-sectional mail survey. PARTICIPANTS: Minnesota dietitians who treat adult outpatients referred by physicians for hypercholesterolemia. MAIN OUTCOME MEASURES: Proportion of patients for whom background information or specific diet instructions were provided by referring physicians and for whom follow-up was recommended and dietary fat content calculated by the dietitians. RESULTS: Completed questionnaires were returned by 216 of 267 eligible dietitians (81% response rate). Respondents saw, on average, 31 referred patients per month, 31% of whom were referred for hypercholesterolemia, 31% for type II diabetes mellitus, and 24% for obesity. For patients referred for hypercholesterolemia, background information was provided by physicians 37% of the time, and specific diet instructions 15% of the time. One or more follow-up visits by the dietitians were recommended for 42% of patients referred for hypercholesterolemia, compared with 60% and 70% of patients referred for diabetes and obesity, respectively. The average number of additional visits within 6 months of the initial consultation recommended by dietitians was 2.0 for patients referred for hypercholesterolemia, 3.5 for patients referred for diabetes, and 6.7 for patients referred for obesity, and the number of visits that occurred was half or less than that recommended. Dietary fat content was calculated by the dietitians for only 25% of patients referred for hypercholesterolemia. CONCLUSIONS: For adult outpatients referred to dietitians for hypercholesterolemia, relevant patient information is usually not provided by referring physicians, the number of follow-up visits is well below what would reasonably be expected to produce significant and sustained eating behavior change, and calculation of dietary fat content is generally not done. More research is needed to determine appropriate nutrition intervention protocols for these patients.

Adult↗
PubMed1994

Predictors of cancer prevention attitudes and participation in cancer screening examinations.

BACKGROUND: Few current data are available regarding factors associated with participation in cancer screening examinations in the general population. METHODS: To identify factors associated with participation in cancer screening examinations, random population samples of 25- to 74-year-old men and women in six various-sized communities in three upper-Midwestern states (n = 4,915) were surveyed in 1987-1989. Multivariate-adjusted means were calculated and compared using analysis of covariance. RESULTS: Statistically significant (P < 0.05) strong predictors (other than age and sex) of ever having had a specific cancer screening test were as follows (the numbers in parentheses following each listed association are the absolute maximum differences in mean proportions among the levels of the predictors): (1) rectal examination: higher education (14%); (2) fecal occult blood testing: higher education (6%) and never smoker (5%); (3) sigmoidoscopy: higher income (7%) and higher education (6%); and (5) mammography: higher income (25%), higher education (8%), and a positive family history of breast cancer (7%). There were no strong predictors (out of nine) of ever having had a Papanicolaou smear or a breast self-examination. CONCLUSIONS: The largest differences among the population for participation in cancer screening examinations involves income and the two most expensive cancer screening tests: higher income is a strong predictor of having a mammogram and, to a lesser extent, of having a sigmoidoscopy. The most consistent predictor of participation in cancer screening examinations across all cancer screening tests is education: higher education is a predictor of having each kind of cancer screening test.

Adult↗
PubMed1994

Dietary cholesterol, fat, and lung cancer incidence among older women: the Iowa Women's Health Study (United States).

To test the hypothesis that a high intake of dietary cholesterol and fat is associated with elevated risks of lung cancer, we analyzed data from a population-based, prospective, cohort study conducted among 41,837 postmenopausal Iowa (United States) women who completed, in 1986, a comprehensive mailed questionnaire including information on usual intake of 127 food items. All cohort members were followed for cancer incidence through the statewide cancer registry. By 1991, after six years of follow-up, 272 incident lung-cancer cases were identified. After controlling for total energy intake and other confounding factors, dietary cholesterol, total fat, and animal fat were unrelated to lung cancer risk. Intake in the upper three quartiles of plant-derived fat, however, was related to a 30 to 40 percent lower incidence of lung cancer, comparative with those in the lowest quartile, with more pronounced reduction in risk observed among smokers (relative risk = 0.6, 95 percent confidence interval = 0.4-0.9). This prospective cohort study suggests that high intake of fat of plant origin may be associated with reduced risk of lung cancer, while dietary cholesterol and animal fat intake is unrelated to the etiology of this malignancy in postmenopausal women.

Animal Population Groups↗
PubMed1994

Sugar, meat, and fat intake, and non-dietary risk factors for colon cancer incidence in Iowa women (United States).

To investigate the relation of dietary intakes of sucrose, meat, and fat, and anthropometric, lifestyle, hormonal, and reproductive factors to colon cancer incidence, data were analyzed from a prospective cohort study of 35,215 Iowa (United States) women, aged 55-69 years and without a history of cancer, who completed mailed dietary and other questionnaires in 1986. Through 1990, 212 incident cases of colon cancer were documented. Proportional hazards regression was used to adjust for age and other risk factors. Risk factors found to be associated significantly with colon cancer included: (i) sucrose-containing foods and beverages other than ice cream/milk; relative risks (RR) across the quintiles = 1.00, 1.73, 1.56, 1.54, and 2.00 (95% confidence intervals [CI] for quintiles two and five exclude 1.0); (ii) sucrose; RR across the quintiles = 1.00, 1.70, 1.81, 1.82, and 1.45 (CI for quintiles two through four exclude 1.0); (iii) height; RR = 1.23 for highest to lowest quintile (P for trend = 0.02); (iv) body mass index; RR = 1.41 for highest to lowest quintile (P for trend = 0.03); and (v) number of livebirths, RR = 1.59 for having had one to two livebirths and 1.80 for having had three or more livebirths compared with having had none (P for trend = 0.04). These data support hypotheses that sucrose intake or being tall or obese increases colon cancer risk; run contrary to the hypothesis that increased parity decreases risk; support previous findings of no association with demographic factors other than age, cigarette smoking, or use of oral contraceptives or estrogen replacement therapy; and raise questions regarding previous associations with meat, fat, protein, and physical activity.

Age Factors↗
PubMed1993

Association of body fat distribution and family histories of breast and ovarian cancer with risk of postmenopausal breast cancer.

The authors recently published data from a prospective cohort study of postmenopausal women (N Engl J Med 1992;326:1323-9) which suggested that a high waist/hip ratio was associated with a significantly increased risk of breast cancer in women with a positive family history of breast cancer. Since families with aggregations of breast and ovarian cancer demonstrate more consistent genetic linkage to markers on chromosome 17q than do families with breast cancer alone, the authors performed additional analyses to examine whether the previously observed associations with waist/hip ratio differed when family history of breast cancer was partitioned according to whether or not ovarian cancer was also present in a close relative. Between 1986 and 1990, 620 incident cases of breast cancer were identified in a cohort of 37,105 postmenopausal Iowa women. A family history of breast cancer in first-degree relatives was associated with a relative risk of 1.34 (95% confidence interval (CI) 1.07-1.69); a family history of both breast cancer and ovarian cancer was associated with a relative risk of 2.36 (95% CI 1.12-4.98). Consistent with the authors' findings after 4 years of follow-up, a high waist/hip ratio (> or = 80th percentile vs. < 80th percentile) was associated with increased risk of breast cancer in the presence of a family history of breast cancer (relative risk (RR) = 2.10, 95% CI 1.43-3.09) but not in the absence of a family history of breast cancer (RR = 1.12). The combination of a high waist/hip ratio with a family history of breast and ovarian cancer was associated with 4.83-fold increased risk (95% CI 1.55-15.1). Neither a family history of breast cancer nor a family history of ovarian cancer was associated with significantly increased risk in the absence of a high waist/hip ratio.

Adipose Tissue↗
PubMed1993

Reduced risk of colon cancer with high intake of vitamin E: the Iowa Women's Health Study.

Antioxidant micronutrients, including vitamin E, vitamin C, the carotenoids, and selenium, defend the body against free radicals and reactive oxygen molecules, suggesting a potential for these dietary components in cancer prevention. To investigate whether high intakes of antioxidant micronutrients protect against colon cancer in humans, we analyzed data from a prospective cohort study of 35,215 Iowa women aged 55-69 years and without a history of cancer who completed a dietary questionnaire in 1986. Through 1990, 212 incident cases of colon cancer were documented. Adjusted for age, total vitamin E intake was inversely associated with the risk of colon cancer (P for trend < 0.0001); the relative risk for the highest compared to the lowest quintile was 0.32 [95% confidence interval (95% CI) 0.19, 0.54]. Further adjustment for total energy intake and other risk factors in proportional hazards regression had little effect on these estimates. The association was not uniform across age groups: the multivariate relative risk of colon cancer for the highest compared to the lowest quintile of total vitamin E intake was 0.16 (95% CI 0.04, 0.70) for those 55-59 years old, 0.37 (95% CI 0.12, 1.16) for those 60-64 years old, and 0.93 (95% CI 0.27, 3.25) for those 65-69 years old. Multivariate-adjusted relative risks among women with higher total intakes of vitamins A and C and beta-carotene, and among users of selenium supplements, were not significantly different from 1.0. These prospective data provide evidence that a high intake of vitamin E may decrease the risk of colon cancer, especially in persons under 65 years of age.

Aged↗
PubMed1993

Relation of calcium, vitamin D, and dairy food intake to incidence of colon cancer among older women. The Iowa Women's Health Study.

To investigate whether a high intake of calcium, vitamin D, or dairy products may protect against colon cancer, the authors analyzed data from a prospective cohort study of 35,216 Iowa women aged 55-69 years without a history of cancer who completed a dietary questionnaire in 1986. Through 1990, 212 incident cases of colon cancer were documented. Adjusted for age, intakes of calcium and vitamin D were significantly inversely associated with the risk of colon cancer. The relative risks for the highest quintile of intake as compared with the lowest were 0.52 (95% confidence interval (CI) 0.33-0.82) for calcium and 0.54 (95% CI 0.35-0.84) for vitamin D. After multivariate adjustment, the trends were no longer statistically significant and the relative risks for the highest versus the lowest quintiles of calcium and vitamin D intakes were attenuated: 0.68 (95% CI 0.41-1.11) for calcium and 0.73 (95% CI 0.45-1.18) for vitamin D. Although the multivariate-adjusted findings did not reach statistical significance at p < or = 0.05, when considered in the context of the whole body of literature on this subject, they are consistent with a possible role for calcium or vitamin D in modestly reducing colon cancer risk.

Aged↗
PubMed1993

Calcium and colorectal epithelial cell proliferation: a preliminary randomized, double-blinded, placebo-controlled clinical trial.

BACKGROUND: Colonic epithelial cell proliferation is increased in patients at high risk for colon cancer. Calcium administration has ameliorated the proliferative changes in rodents, and findings in small, uncontrolled clinical trials have suggested similar effects in humans. PURPOSE: This preliminary, double-blind, randomized clinical trial was designed 1) to investigate whether supplemental calcium will reduce colonic epithelial cell proliferation in patients with sporadic adenomas who consume a high-fat, Western-style diet; 2) to determine the sample size (number of scorable crypts per person) needed to achieve adequate statistical power; and 3) to evaluate the feasibility of full-scale clinical trials. METHODS: Twenty-one sporadic adenoma patients were treated daily with placebo or 1200 mg of supplemental calcium. To determine colonic epithelial cell proliferation, we used tritiated thymidine labeling of colon crypt epithelial cells in rectal biopsy specimens and calculated the percentage of labeled cells (labeling index [LI]). Two pathology technician "readers" independently scored each specimen, and inter-reader reliability was determined. Subjects remained on their usual diet during the study, and intake of calories, calcium, total fat, and vitamin D did not differ substantially among them. We calculated curves for statistical power to determine the number of scorable crypts needed per person for detection of a statistically significant difference (P < .05) of 1.0% in mean LI. RESULTS: The pooled baseline LI was 4.7%. In the calcium-treated group, the LI increased 0.6% (proportional increase, 12.8%); in the placebo-treated group, it decreased 0.5% (proportional decrease, 10.6%). The difference between change in the mean LI from baseline to 8 weeks' follow-up in the placebo group versus the calcium group was not statistically significant. The intraclass correlation coefficient for inter-reader reliability for the baseline LI was .66. Analyses indicated scoring eight crypts sufficient for estimates of the LI adequate for between-group comparisons, a level achieved in 81% of biopsy specimens. CONCLUSIONS: Calcium carbonate supplements delivering 1200 mg elemental calcium daily may not decrease colonic epithelial cell proliferation over an 8-week period in sporadic adenoma patients. In future trials measuring the LI, consideration should be given to ensuring adequate numbers of scorable crypts and to the impact of inadequate biopsy procedures, labeling failure, reader reliability, and participant withdrawal. Our findings support the feasibility of a full-scale clinical trial to further study the relationships among dietary calcium, colonic epithelial cell proliferation, and colorectal cancer.

Adenoma↗