Internalized homonegativity/homophobia is associated with HIV-risk behaviours among Ugandan gay and bisexual men.

We investigated the relationship of internalized homonegativity/homophobia (IH) to sexual risk behaviours among 216 Ugandan gay and bisexual men, using the 7-item IH scale previously developed on this population. IH was significantly associated with unprotected anal intercourse, and more so with unprotected receptive anal intercourse. Higher IH was also associated with more sex while intoxicated. There was a strong association between anal intercourse of any type and IH, suggesting a complex relationship between anal sex and identification with, or internalization of, homonegativity/homophobia. Specifically, it may be the anal component of sex rather than the sex with another man that is seen as labeling one as homosexual or stigmatizing. Those men who stated that they engaged in sex with other men for love, rather than for the physical feeling or for money, had higher IH scores. These data suggest that there may be an interactive relationship between IH and sexual behaviour, with greater internalization being associated with more stereotypically gay activities, which in turn may lead to more self-identification as gay and thus greater susceptibility to internalization.

Paraquat and Parkinson's disease: an overview of the epidemiology and a review of two recent studies.

OBJECTIVE: This paper reviews and evaluates two recent epidemiologic studies focused on pesticides, and in particular, paraquat as a cause of PD. Both studies are derived primarily from the Agricultural Health Study (AHS). A review and evaluation is also provided on the AHS and several additional studies of paraquat and PD. METHODS: The methods used to design and conduct the studies and analyze the data are described and evaluated. RESULTS: Studies were inadequately designed and often underpowered with very few exposed individuals. They were not population-based, failed to distinguish incident from prevalent cases, relied on multiple comparisons, and may have reported results selectively. The results across the studies are inconsistent. CONCLUSIONS: The inherent difficulties of studying Parkinson's disease in relation to paraquat or other pesticides are well illustrated by these studies. A conclusion regarding these relationships cannot be reached based on the current literature. Further research with higher methodological standards is needed to reach a definitive conclusion.

The Upper Midwest Health Study: a case-control study of primary intracranial gliomas in farm and rural residents.

Since several studies indicated that farmers and agricultural workers had an excess risk of brain cancer, the National Institute for Occupational Safety and Health initiated the Upper Midwest Health Study to examine risk of intracranial glioma in the non-metropolitan population. This population-based, case-control study evaluated associations between gliomas and rural and farm exposures among adults (ages 18 to 80) in four upper midwestern states (Iowa, Michigan, Minnesota, Wisconsin). At diagnosis/selection, participants lived in non-metropolitan counties where the largest population center had fewer than 250,000 residents. Cases were diagnosed 1 January 1995 through 31 January 1997. Over 90% of 873 eligible ascertained cases and over 70% of 1670 eligible controls consented to participate. Participants and nonparticipants, evaluated for "critical questions" on main and refusant questionnaires, differed significantly in farming and occupational experience, ethnicity, education, and lifestyle. The 1,175 controls were more likely than the 798 cases to have reported ever drinking alcohol (77% vs. 73%, adjusted odds ratio (OR) 0. 73, 95% confidence interval (CI) 0.59-0.92) and having had panoramic dental x-rays (34% vs. 29%, OR 0. 75, CI 0.61-0.92). Controls spent a greater percentage of their lives in non-metropolitan counties (78% vs. 75%, OR 0.81, CI 0.67-1.09). Among ever-farmers, controls were more likely to have had exposure to farm insecticides (57% vs. 50%, OR 0.75, CI 0.59-0.95) and farm animals (96% vs. 91%, OR 0.48, CI 0.25-0.90). Moving to a farm as an adolescent (ages 11 to 20) vs. as an adult was associated with a greater risk of glioma. In our study sample, farm or rural residence and summary farm exposures were associated with decreased glioma risk. However, nonparticipation by never-farming eligible controls could have affected results. Comparisons of farm chemical exposures may clarify associations between farming and glioma that others have reported.

Mortality of employees of a perfluorooctanesulphonyl fluoride manufacturing facility.

AIM: To evaluate the mortality experience of a cohort of employees of a perfluorooctanesulphonyl fluoride (POSF) based fluorochemical production facility. METHODS: A retrospective cohort mortality study followed all workers with at least one year of cumulative employment at the facility. The jobs held by cohort members were assigned to one of three exposure subgroups; high exposed, low exposed, and non-exposed, based on biological monitoring data for perfluorooctane sulphonate (PFOS). RESULTS: A total of 145 deaths were identified in the 2083 cohort members. Sixty five deaths occurred among workers ever employed in high exposed jobs. The overall mortality rates for the cohort and the exposure subcohorts were lower than expected in the general population. Two deaths from liver cancer were observed in the workers with at least one year of high or low exposure (standardised mortality ratio (SMR) 3.08, 95% CI 0.37 to 11.10). The risk of death from bladder cancer was increased for the entire cohort (three observed, SMR 4.81, 95% CI 0.99 to 14.06). All three bladder cancers occurred among workers who held a high exposure job (SMR 12.77, 95% CI 2.63 to 37.35). The bladder cancer cases primarily worked in non-production jobs, including maintenance and incinerator and wastewater treatment plant operations. CONCLUSION: Workers employed in high exposure jobs had an increased number of deaths from bladder cancer; however it is not clear whether these three cases can be attributed to fluorochemical exposure, an unknown bladder carcinogen encountered during the course of maintenance work, and/or non-occupational exposures. With only three observed cases the possibility of a chance finding cannot be ruled out.

Risk of prevalent HIV infection associated with incarceration among injecting drug users in Bangkok, Thailand: case-control study.

OBJECTIVES: To identify risks for HIV infection related to incarceration among injecting drug users in Bangkok, Thailand. DESIGN: Case-control study of sexual and parenteral exposures occurring before, during, and after the most recent incarceration. SETTING: Metropolitan Bangkok. PARTICIPANTS: Non-prison based injecting drug users formerly incarcerated for at least six months in the previous five years, with documented HIV serostatus since their most recent release; 175 HIV positive cases and 172 HIV negative controls from methadone clinics. MAIN OUTCOME MEASURE: Injection of heroin and methamphetamine, sharing of needles, sexual behaviour, and tattooing before, during, and after incarceration. RESULTS: In the month before incarceration cases were more likely than controls to have injected methamphetamine and to have borrowed needles. More cases than controls reported using drugs (60% v 45%; P=0.005) and sharing needles (50% v 31%; P<0.01) in the holding cell before incarceration. Independent risk factors for prevalent HIV infection included injection of methamphetamine before detention (adjusted odds ratio 3.3, 95% confidence interval 1.01 to 10.7), sharing needles in the holding cell (1.9, 1.2 to 3.0), being tattooed while in prison (2.1, 1.3 to 3.4), and borrowing needles after release (2.5, 1.3 to 4.4). CONCLUSIONS: Injecting drug users in Bangkok are at significantly increased risk of HIV infection through sharing needles with multiple partners while in holding cells before incarceration. The time spent in holding cells is an important opportunity to provide risk reduction counselling and intervention to reduce the incidence of HIV.

A meta-analysis of cohort studies describing mortality and cancer incidence among chemical workers in the United States and western Europe.

We evaluated the mortality and cancer experience of employees of the chemical industry in the United States and western Europe, as reported in the peer-reviewed literature between 1966 and 1997 (>1 million workers and >15 million person-years). Cohort studies (N = 461) were grouped (N = 181) so that specific populations could be traced from the earliest to the most recently published report, and we extracted observed and expected numbers of cases for each of 35 mortality and 23 cancer incidence endpoints. We then generated standardized mortality ratios or standardized incidence ratios and 95% confidence intervals, and undertook meta-analyses of subcohorts (for example, gender, latency, or duration of employment), as well as the entire cohort. With few exceptions, the observed cause-specific mortality and site-specific cancer incidences were reassuring: overall, 10% fewer deaths were observed than expected. Fewer than expected deaths from all causes, cardiovascular disease, noncancer respiratory disease, cirrhosis of the liver, and external causes were observed, some or all of which may be attributed to a "healthy worker effect." Meta-analyses revealed weak to moderate excesses of lung and bladder cancers likely caused by occupational exposure to known human carcinogens. We also observed a 10-15% increase in lymphatic and hematopoietic cancers. Additional research is required to gain a more complete understanding of the potential role that methodology and environmental or occupational influences may play in these associations.

MRI for detecting silicone breast implant rupture: meta-analysis and implications.

The objective of this study was to assess the accuracy of magnetic resonance imaging (MRI) in detecting silicone breast implant rupture, and to explore implications of the use of MRI for screening and estimating the prevalence of rupture among asymptomatic women. The study consisted of a meta-analysis of published studies with the calculation of sensitivity and specificity as independent parameters, the summary receiver operating characteristic (ROC) curve, and other clinically important values such as positive predictive value (PPV) and negative predictive value. Participants included women with breast implants who underwent both MRI and subsequent implant removal. Eighteen studies, performed primarily in academic settings, with approximately 1,039 women and 2,036 implants met entry criteria. Most studies involved women with symptomatic implants. Assuming that sensitivity and specificity were independent parameters, the summary sensitivity was 78% (95% confidence interval [CI], 71-83) and the summary specificity was 91% (95% CI, 86-94). Using ROC meta-analysis methodology, the odds ratio describing the overall accuracy of the test was 40.1 (range, 18.8-85.4). There was substantial heterogeneity across studies. Studies using breast coils, those with convenience samples, larger studies, and studies of lower report quality tended to report higher levels of accuracy. The quality of study reports was generally poor. Among symptomatic women, PPV was fairly high. Among lower prevalence populations, PPV appeared to be insufficient to warrant use as a screening tool. MRI is moderately accurate in detecting silicone breast implant rupture. However, MRI should remain a confirmatory diagnostic test and should not be used to screen asymptomatic women.

The effect of fecal occult-blood screening on the incidence of colorectal cancer.

BACKGROUND: Both annual testing for fecal occult blood and biennial testing significantly reduce mortality from colorectal cancer. However, the effect of screening on the incidence of colorectal cancer remains uncertain, despite the diagnosis and removal of precancerous lesions in many persons who undergo screening. METHODS: We followed the participants in the Minnesota Colon Cancer Control Study for 18 years. A total of 46,551 people, most of whom were 50 to 80 years old, were enrolled between 1975 and 1978 and randomly assigned to annual screening, biennial screening, or usual care (the control group). Those assigned to the screening groups were asked to prepare and submit two samples from each of three consecutive stools for guaiac-based testing. Those with at least one positive slide in the set of six were offered a diagnostic examination that included colonoscopy. Screening was conducted between 1976 and 1982 and again between 1986 and 1992. Study participants have been followed with respect to newly diagnosed cases of colorectal cancer and deaths. Follow-up has been more than 90 percent complete. RESULTS: During the 18-year follow-up period, we identified 1359 new cases of colorectal cancer: 417 in the annual-screening group, 435 in the biennial-screening group, and 507 in the control group. The cumulative incidence ratios for colorectal cancer in the screening groups as compared with the control group were 0.80 (95 percent confidence interval, 0.70 to 0.90) and 0.83 (95 percent confidence interval, 0.73 to 0.94) for the annual-screening and biennial-screening groups, respectively. For both screening groups, the number of positive slides was associated with the positive predictive value both for colorectal cancer and for adenomatous polyps at least 1 cm in diameter. CONCLUSIONS: The use of either annual or biennial fecal occult-blood testing significantly reduces the incidence of colorectal cancer.

Safe handling of agricultural pesticides in Minnesota: results of a county-wide educational intervention.

Safe pesticide handling in a group of Minnesota farmers, aged 40 years and older, was influenced through the use of a multifaceted, countywide educational intervention. Two intervention counties and two control counties were involved in this effort. The intervention consisted of mailed pesticide information to farm households, educational programs on pesticides for county physicians, elementary school training modules on pesticides and the use of safe pesticide handling displays in key business areas by agricultural extension agents. Five hundred eight farmers were identified as pesticide users (186 in the intervention counties and 322 in the control counties). The use of gloves and other protective clothing while handling pesticides increased in the intervention group. Improvement was greater in those who had used protective equipment the least before the intervention. From these results, it appears that a broad-based educational intervention might have a modest impact in how farmers protect themselves when using pesticides.

Rectal mucosal proliferation and risk of colorectal adenomas: results from a randomized controlled trial.

Although rectal mucosal labeling index is thought to be a useful surrogate biomarker for colorectal cancer, the ability of the index to predict future neoplasia is unclear. We obtained rectal mucosal biopsies from 333 participants of a randomized controlled chemoprevention trial of calcium supplementation to determine whether labeling index was correlated with concurrent or future colorectal neoplasms. Labeling index was measured using proliferating cell nuclear antigen immunohistochemistry. Adenomas were enumerated at the time of the biopsies (cross-sectional) and 3 years later (prospective). We used logistic regression to test for an association of adenoma occurrence with overall labeling index, the mean proliferative height, and labeling index in the upper 40% of colon crypts. In the cross-sectional analysis, we found indications that higher proliferation was associated with an increase in the prevalence of adenomas. The overall adjusted odds ratios (OR) (95% confidence interval) were 1.14 (0.90-1.45) per % crypt labeling index, OR 1.08 (0.99-1.19) for upper crypt proliferation, and OR 1.07 (1.03-1.12) for proliferative height. In contrast, individuals with higher labeling index at baseline were actually less likely to have adenomas in the prospective analyses: OR 0.80 (0.62-1.02) per % crypt labeling index, OR 0.86 (0.73-1.00) for upper crypt index, and OR 0.97 (0.93-1.01) for proliferative height. Proliferative index does not predict future colorectal neoplasia, although it may be weakly associated with the presence of current adenomas. These results have important implications for the design of future intervention studies. Although it may be attractive to include the measurement of intermediate markers in large controlled trials, until we have more confidence in their performance, we should rely on better proven and more reliable intermediates, such as adenomas.

Mortality among Catholic nuns certified as radiologic technologists.

BACKGROUND: Several studies have shown that Catholic nuns have a different mortality experience than women of similar age in the general population. We had a unique opportunity to evaluate mortality patterns of nuns identified in an occupational study of nearly 145,000 radiologic technologists (73% female). METHODS: A total of 1,103 women were classified as nuns based on their titles of "Sister" or "SR". Their mortality experience was compared to other female radiologic technologists and to U.S. white females. RESULTS: Five hundred eighty-three nuns (53%) were deceased as of January 1, 1995. Compared to other technologists, nuns were at significantly increased risk of dying from all causes (Standardized mortality ratio (SMR)=1.1; 95% Confidence interval (CI)=1.0-1.2, stomach cancer (SMR=2.7; 95% CI=1.2-5.4), diabetes (SMR=2.2; 95% CI=1.0-4.1), ischemic heart disease (SMR=1.2; 95% CI=1.1-1.4), all digestive diseases (SMR=2.0; 95% CI=1.3-3.0), and gastric and duodenal ulcers (SMR=8.3; 95% CI=2.3-21.3). In contrast, we observed a significant deficit in lung cancer (SMR=0.5; 95% CI=0.2-0.9), no deaths from cervical cancer, and a breast cancer risk 10% lower than expected (SMR=0.9; 95% CI=0.6-1.3). When compared to U.S. females, nuns experienced significantly reduced mortality from all causes (SMR=0.8; 95% CI=0.7-0.9), cervical cancer (SMR=0.0; 95% CI=0.0-0.7), all endocrine, metabolic and nutritional diseases (SMR=0.5; 95% CI=0.3-0.9), all circulatory diseases (SMR=0.7; 95% CI=0.7-0.8) including ischemic heart disease and cerebrovascular disease, and all respiratory diseases (SMR=0.5; 95% CI=0.3-0.8), and a nearly significant deficit of diabetes (SMR=0.6; 95% CI=0.3-1.0). In contrast, nuns had an almost 3-fold greater risk of tuberculosis (SMR=2.9; 95% CI=1.4-5.3) and a 20% excess of breast cancer (SMR=1. 2; 95% CI=0.8-1.7). The breast cancer excess was concentrated among nuns first certified before 1940 (SMR=2.0; CI=1.3-3.0), when radiation doses were possibly the highest, but the risk did not increase with increasing length of certification. CONCLUSIONS: Compared with the general population, the mortality experience of nuns was favorable and reflected the "healthy worker effect" commonly seen in occupational studies. Patterns observed for breast and cervical cancer possibly indicate differences in reproductive and sexual activities associated with belonging to a religious order. The possibility of a radiation-related excess for breast cancer among nuns certified before 1940 cannot be completely discounted, although there was no dose-response relationship with a surrogate measure of exposure (number of years certified). When their mortality experience was compared with other radiologic technologists, the influence of lifestyle factors was not apparent. Am. J. Ind. Med. 37:339-348, 2000. Published 2000 Wiley-Liss, Inc. dagger

Design of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

The objectives of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial are to determine in screenees ages 55-74 at entry whether screening with flexible sigmoidoscopy (60-cm sigmoidoscope) can reduce mortality from colorectal cancer, whether screening with chest X-ray can reduce mortality from lung cancer, whether screening men with digital rectal examination (DRE) plus serum prostate-specific antigen (PSA) can reduce mortality from prostate cancer, and whether screening women with CA125 and transvaginal ultrasound (TVU) can reduce mortality from ovarian cancer. Secondary objectives are to assess screening variables other than mortality for each of the interventions including sensitivity, specificity, and positive predictive value; to assess incidence, stage, and survival of cancer cases; and to investigate biologic and/or prognostic characterizations of tumor tissue and biochemical products as intermediate endpoints. The design is a multicenter, two-armed, randomized trial with 37,000 females and 37,000 males in each of the two arms. In the intervention arm, the PSA and CA125 tests are performed at entry, then annually for 5 years. The DRE, TVU, and chest X-ray exams are performed at entry and then annually for 3 years. Sigmoidoscopy is performed at entry and then at the 5-year point. Participants in the control arm follow their usual medical care practices. Participants will be followed for at least 13 years from randomization to ascertain all cancers of the prostate, lung, colorectum, and ovary, as well as deaths from all causes. A pilot phase was undertaken to assess the randomization, screening, and data collection procedures of the trial and to estimate design parameters such as compliance and contamination levels. This paper describes eligibility, consent, and other design features of the trial, randomization and screening procedures, and an outline of the follow-up procedures. Sample-size calculations are reported, and a data analysis plan is presented.

Analysis of chlorpyrifos exposure and human health: expert panel report.

This report summarizes the deliberations of an eight-member panel of scientists convened by Dow AgroSciences in cooperation with the U.S. Environmental Protection Agency (EPA). The panel was charged with evaluating the scientific literature on the health effects potentially associated with exposure to the insecticide chlorpyrifos. Specifically, the panel was asked to (1) evaluate human experience data available and address the adequacy of the available current literature; (2) develop a list of recommendations for epidemiology studies, including appropriate endpoints and study populations, and strengths and weaknesses of each approach; and (3) draft a report to summarize its recommendations. The panel assessed the quality of the existing epidemiologic literature on chlorpyrifos and specific outcomes such as neuropathy (including organophosphate induced delayed neurotoxicity), behavior (cognition and affect), immunologic, and multiple complaints (also referred to as multiple chemical sensitivities). The majority of panel members (five members) agreed that the literature reviewed provided little or no scientific evidence that chlorpyrifos exposure causes harm to human health other than its known cholinergic effects associated with acute poisoning. Those panel members voting in the minority (three members) agreed that the studies reviewed provided inadequate evidence to preclude the possibility of adverse effects to human health from chlorpyrifos exposure at levels associated with its manufacture or professional application. Those voting in the minority suggested further investigation of cohort(s) of workers engaged in either the manufacture or the professional application of chlorpyrifos, or both. Compared to the general population, these groups have relatively high levels of exposure to chlorpyrifos. The primary health outcomes recommended for study were cognitive and affective disorders, with consideration of the assessment of peripheral neuropathy also suggested for at least a subset of the cohort.

Colorectal cancer deaths as determined by expert committee and from death certificate: a comparison. The Minnesota Study.

For deaths during the first 13 years of follow-up of the Minnesota Colon Cancer Control Study, an expert committee using numerous medical documents, and a nosologist using only the death certificate independently determined whether colorectal cancer caused the death and, if not, whether the disease was present at death. Deaths due to colorectal cancer numbered 318 according to the nosologist and 323 according to the committee, a discrepancy of 1.5%, which is similar in magnitude to that in three previous studies. The nosologist and committee agreed that colorectal cancer caused the death in each of 290 individual cases; they disagreed widely on the number of deaths from other causes but with colorectal cancer. If it is important to know only the gross number of deaths from colorectal cancer, then the death certificate alone appears to be sufficiently accurate; if it is important to know the cause of death of individual subjects or the number dying from other causes but with colorectal cancer, then the expert committee method provides more accurate information.

Colorectal cancer mortality: effectiveness of biennial screening for fecal occult blood.

BACKGROUND: In 1993, a randomized controlled trial in Minnesota showed, after 13 years of follow-up, that annual fecal occult blood testing was effective in reducing colorectal cancer mortality by at least 33%. Biennial screening (i.e., every 2 years) resulted in only a 6% mortality reduction. Two European trials (in England and in Denmark) subsequently showed statistically significant 15% and 18% mortality reductions with biennial screening. Herein, we provide updated results-through 18 years of follow-up--from the Minnesota trial that address the apparent inconsistent findings among the trials regarding biennial screening. METHODS: From 1976 through 1977, a total of 46551 study subjects, aged 50-80 years, were recruited and randomly assigned to an annual screen, a biennial screen, or a control group. A screen consisted of six guaiac-impregnated fecal occult blood tests (Hemoccult) prepared in pairs from each of three consecutive fecal samples. Participants with at least one of the six tests that were positive were invited for a diagnostic examination that included colonoscopy. All participants were followed annually to ascertain incident colorectal cancers and deaths. RESULTS: The numbers of deaths from all causes were similar among the three study groups. Cumulative 18-year colorectal cancer mortality was 33% lower in the annual group than in the control group (rate ratio, 0.67; 95% confidence interval [CI] = 0.51-0.83). The biennial group had a 21% lower colorectal cancer mortality rate than the control group (rate ratio, 0.79; 95% CI = 0.62-0.97). A marked reduction was also noted in the incidence of Dukes' stage D cancers in both screened groups in comparison with the control group. CONCLUSION: The results from this study, together with the other two published randomized trials of fecal occult blood screening, are consistent in demonstrating a substantial, statistically significant reduction in colorectal cancer mortality from biennial screening.

Calcium supplements for the prevention of colorectal adenomas. Calcium Polyp Prevention Study Group.

BACKGROUND AND METHODS: Laboratory, clinical, and epidemiologic evidence suggests that calcium may help prevent colorectal adenomas. We conducted a randomized, double-blind trial of the effect of supplementation with calcium carbonate on the recurrence of colorectal adenomas. We randomly assigned 930 subjects (mean age, 61 years; 72 percent men) with a recent history of colorectal adenomas to receive either calcium carbonate (3 g [1200 mg of elemental calcium] daily) or placebo, with follow-up colonoscopies one and four years after the qualifying examination. The primary end point was the proportion of subjects in whom at least one adenoma was detected after the first follow-up endoscopy but up to (and including) the second follow-up examination. Risk ratios for the recurrence of adenomas were adjusted for age, sex, lifetime number of adenomas before the study, clinical center, and length of the surveillance period. RESULTS: The subjects in the calcium group had a lower risk of recurrent adenomas. Among the 913 subjects who underwent at least one study colonoscopy, the adjusted risk ratio for any recurrence of adenoma with calcium as compared with placebo was 0.85 (95 percent confidence interval, 0.74 to 0.98; P=0.03). The main analysis was based on the 832 subjects (409 in the calcium group and 423 in the placebo group) who completed both follow-up examinations. At least one adenoma was diagnosed between the first and second follow-up endoscopies in 127 subjects in the calcium group (31 percent) and 159 subjects in the placebo group (38 percent); the adjusted risk ratio was 0.81 (95 percent confidence interval, 0.67 to 0.99; P=0.04). The adjusted ratio of the average number of adenomas in the calcium group to that in the placebo group was 0.76 (95 percent confidence interval, 0.60 to 0.96; P=0.02). The effect of calcium was independent of initial dietary fat and calcium intake. CONCLUSIONS: Calcium supplementation is associated with a significant - though moderate - reduction in the risk of recurrent colorectal adenomas.

N-acetylcysteine suppression of the proliferative index in the colon of patients with previous adenomatous colonic polyps.

This investigation is part of an effort to develop chemoprevention for carcinogenesis of the large bowel. The agent investigated is N-acetylcysteine (NAC). We used as a predictive biomarker, the proliferative index (PI), in a short-term human study. Patients with previous adenomatous colonic polyps are a cohort with increased risk for colon cancer and an increased PI of colonic crypts. They were randomly assigned to an experimental group given 800 mg/day of NAC for 12 weeks or a placebo group. Using proliferative cell nuclear antigen immunostaining, the PI of colonic crypts was measured prior to and after the treatments. The PI of the NAC group was decreased significantly (P < 0.02) while the placebo group showed no difference (P > 0.45). Since this decrease in PI may be an indicator of decreased risk of colon cancer, more extensive studies of the potential of NAC as a chemopreventive agent for colon cancer appear warranted.

Calcium supplements and colorectal adenomas. Polyp Prevention Study Group.

Experimental and observational findings suggest that calcium intake may protect against colorectal neoplasia. To investigate this hypothesis, we conducted a randomized, double-blind trial of colorectal adenoma recurrence. Nine hundred thirty patients with a recent history of colorectal adenomas were randomly given calcium carbonate (3 gm daily; 1200 mg elemental calcium) or placebo, with follow-up colonoscopies one and four years after the qualifying examination. The main analysis focused on new adenomas found after the first follow-up endoscopy, up to (and including) the second follow-up examination. Risk ratios of at least one recurrent adenoma and ratios of the average numbers of adenomas were calculated as measures of calcium effect. There was a lower risk of recurrent adenomas in subjects assigned calcium. Eight hundred thirty-two patients had two follow-up examinations and were included in the main analysis; the adjusted risk ratio of one or more adenomas was 0.81 (95% CI 0.67 to 0.99); the adjusted ratio of the average numbers of adenomas was 0.76 (95% CI 0.60 to 0.96). Among subjects who had at least one follow-up colonoscopy, the adjusted risk ratio of one or more recurrent adenomas was 0.85 (95% CI 0.74 to 0.98). The effect of calcium seemed independent of initial dietary fat and calcium intake. No toxicity was associated with supplementation. These findings indicate that calcium supplementation has a modest protective effect against colorectal adenomas, precursors of most colorectal cancers.