Long-term mortality after screening for colorectal cancer.

BACKGROUND: In randomized trials, fecal occult-blood testing reduces mortality from colorectal cancer. However, the duration of the benefit is unknown, as are the effects specific to age and sex. METHODS: In the Minnesota Colon Cancer Control Study, 46,551 participants, 50 to 80 years of age, were randomly assigned to usual care (control) or to annual or biennial screening with fecal occult-blood testing. Screening was performed from 1976 through 1982 and from 1986 through 1992. We used the National Death Index to obtain updated information on the vital status of participants and to determine causes of death through 2008. RESULTS: Through 30 years of follow-up, 33,020 participants (70.9%) died. A total of 732 deaths were attributed to colorectal cancer: 200 of the 11,072 deaths (1.8%) in the annual-screening group, 237 of the 11,004 deaths (2.2%) in the biennial-screening group, and 295 of the 10,944 deaths (2.7%) in the control group. Screening reduced colorectal-cancer mortality (relative risk with annual screening, 0.68; 95% confidence interval [CI], 0.56 to 0.82; relative risk with biennial screening, 0.78; 95% CI, 0.65 to 0.93) through 30 years of follow-up. No reduction was observed in all-cause mortality (relative risk with annual screening, 1.00; 95% CI, 0.99 to 1.01; relative risk with biennial screening, 0.99; 95% CI, 0.98 to 1.01). The reduction in colorectal-cancer mortality was larger for men than for women in the biennial-screening group (P=0.04 for interaction). CONCLUSIONS: The effect of screening with fecal occult-blood testing on colorectal-cancer mortality persists after 30 years but does not influence all-cause mortality. The sustained reduction in colorectal-cancer mortality supports the effect of polypectomy. (Funded by the Veterans Affairs Merit Review Award Program and others.).

A prospectively measured serum biomarker for a tobacco-specific carcinogen and lung cancer in smokers.

BACKGROUND: No prior studies have related a tobacco-specific carcinogen to the risk of lung cancer in smokers. Of the over 60 known carcinogens in cigarette smoke, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is specific to tobacco and causes lung cancer in laboratory animals. Its metabolites, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides (total NNAL), have been studied as biomarkers of exposure to NNK. We studied the relation of prospectively measured NNK biomarkers to lung cancer risk. METHODS: In a case-control study nested in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we randomly selected 100 lung cancer cases and 100 controls who smoked at baseline and analyzed their baseline serum for total NNAL, cotinine, and r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT), a biomarker of polycyclic aromatic hydrocarbon exposure and metabolic activation. To examine the association of the biomarkers with all lung cancers and for histologic subtypes, we computed odds ratios for total NNAL, PheT, and cotinine using logistic regression to adjust for potential confounders. FINDINGS: Individual associations of age, smoking duration, and total NNAL with lung cancer risk were statistically significant. After adjustment, total NNAL was the only biomarker significantly associated with risk (odds ratio, 1.57 per unit SD increase; 95% confidence interval, 1.08-2.28). A similar statistically significant result was obtained for adenocarcinoma risk, but not for nonadenocarcinoma. CONCLUSIONS: This first reporting of the effect of the prospectively measured tobacco-specific biomarker total NNAL, on risk of lung cancer in smokers provides insight into the etiology of smoking-related lung cancer and reinforces targeting NNK for cancer prevention.

Recruitment, retention, and compliance results from a probability study of children's environmental health in economically disadvantaged neighborhoods.

The School Health Initiative: Environment, Learning, and Disease (SHIELD) study used a probability sample of children (second through fifth grades) from two low-income and racially mixed neighborhoods of Minneapolis, Minnesota, to assess childhood environmental health. Children were eligible to participate in SHIELD regardless of whether they or their families spoke a foreign language, their household had a telephone, or they were enrolled in a special education program. The overall enrollment rate in year 1 was 57%, with a substantial disparity between children from English-speaking (42%) versus non-English-speaking (71%) families. At the end of year 1, 85% were retained in the study. A relatively high percentage of children provided the two requested blood (82%) and urine (86%) samples in year 1, and 90% provided a valid spirometry sample. Eighty-two percent provided both requested volatile organic chemical badge samples, and both time-activity logs were obtained from 66%. However, only 32% provided both peak flow measurements. All percentages increased for those participating in the second year of the study. Results indicate that a school-based research design makes it feasible and practical to conduct probability-based assessments of children's environmental health in economically disadvantaged and ethnically diverse neighborhoods. There is an ongoing need, however, to improve understanding of the cultural, economic, psychologic, and social determinants of study participation among this population.

Children's exposure to environmental tobacco smoke: using diverse exposure metrics to document ethnic/racial differences.

Four metrics were used to assess exposure to environmental tobacco smoke (ETS) for a probability sample (n = 152) of elementary school-age children in two economically disadvantaged neighborhoods: a) caregiver responses to a baseline questionnaire (BQ) about smoking status and behavior; b) 48-hr time-activity (T-A) data on location and time spent by children in the presence of tobacco smoke; c) total urinary cotinine as a marker for nicotine uptake; and d) urinary NNAL [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol] + NNAL-Gluc [4-(methylnitrosamino)-1- (3-pyridyl)-1-(O-beta-D-glucopyranuronosyl)butane] as a marker for uptake of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Consistent differences in ETS exposure by ethnicity and race were observed. Although data were insufficient to determine differences for NNAL + NNAL-Gluc, BQ responses, T-A data, and cotinine levels all indicated that average ETS exposure was highest for African-American children, moderately high for those designated "other" (white, Southeast Asian, Native American), moderately low for Hispanic children, and lowest for Somali immigrant children. For example, in February 2000, mean cotinine levels were 14.1 ng/mL for African Americans, 12.2 ng/mL for other, 4.8 ng/mL for Hispanics, and 4.4 ng/mL for Somalis. The BQ and T-A data together were reasonably good predictors of total cotinine levels (adjusted r2 = 0.69), and based on limited data, measured total cotinine values were a relatively good predictor of NNAL + NNAL-Gluc (adjusted r2 = 0.73). The results suggest that when children are exposed to ETS primarily in their homes, questionnaires and T-A logs might be effective screening tools for identifying those likely to experience higher uptake of nicotine.

Case-control study of student-perpetrated physical violence against educators.

PURPOSE: Although prior research focused primarily on student-on-student school violence, educators are also at risk. This study was designed to identify risk factors for assaults against educators. METHODS: Kindergarten-grade 12 educators (n = 26,000), randomly selected from a state license database, were screened for eligibility (6,469, eligible) by mailed questionnaire. Phase 1 (12-month recall) identified eligible assault cases (n = 372) and controls (n = 1,116), June 2004 to December 2005; phase 2 (case-control study; response, 78%) enabled identification of exposures through 1-month recall before student-perpetrated assaults (cases) and randomly selected months (controls). Directed acyclic graphs enabled confounder selection for multivariable logistic regression analyses; reweighting adjusted for potential biases. RESULTS: Risks (odds ratios, 95% confidence intervals) increased for working in: Special Education (5.84; 4.07-8.39) and School Social Work (7.18; 2.72-18.91); kindergarten to second grade (1.81; 1.18-2.77); urban (1.95; 1.38-2.76) schools; schools with less than 50 (8.40; 3.12-22.63), 50-200 (3.67; 1.84-7.34), 201-500 (2.09; 1.32-3.29), and 501-1000 (1.94; 1.25-3.01) students versus more than 1000; schools with inadequate resources always/frequently (1.62; 1.05-2.48) versus infrequently/never; inadequate building safety always/frequently (4.48; 2.54-7.90) versus infrequently/never; and environments with physical barriers (1.50; 1.07-2.10). Risks decreased with routine locker searches (0.49; 0.29-0.85) and accessible exits (0.36; 0.17-0.74). CONCLUSIONS: Identification of assault risk factors provides a basis for further investigation and interventions.

Violence against educators: a population-based study.

OBJECTIVE: Identify the magnitude and risk factors for occupational physical assault (PA) and nonphysical violence (NPV) against Minnesota educators. METHODS: Among 26,000 randomly selected licensed kindergarten to grade 12 educators, 6469 eligible educators reported whether they experienced PA or NPV during the prior year. Multiple logistic regression models were based on directed acyclic graphs. RESULTS: Respective PA and NPV annual rates per 100 educators were 8.3 and 38.4. Work changes resulted among PA (13% to 20%) and NPV (22%) victims. Risks increased for master's prepared or education specialists who worked in public alternative schools and special education. Risks decreased for those working for more than 20 years, part time, and in private schools. Physical assault risk decreased when teaching grades 3 to 12 (vs kindergarten to grade 2), but NPV risk increased. CONCLUSION: Targeted efforts on specific violence risk and protective factors are essential to improve educators' work environments.

Interaction of CYP1B1, cigarette-smoke carcinogen metabolism, and lung cancer risk.

A previously published case-control study nested in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial found a significant relationship of serum levels of total NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides) to prospective lung cancer risk. The present paper examines this relationship in the context of single-nucleotide polymorphisms (SNPs) in genes important in the metabolism of tobacco smoke carcinogens. DNA was extracted from the subjects' lymphocytes and analyzed for SNPs in 11 locations on four genes related to tobacco carcinogen metabolism. Logistic regressions on case-control status were used to estimate main effects of SNPs and biomarkers and their interactions adjusting for potential confounders. Of the 11 SNPs, only one, in CYP1B1, significantly interacted with total NNAL affecting risk for lung cancer. At low NNAL levels, the variant appeared protective. However, for those with the minor variant, the risk for lung cancer increased with increasing NNAL five times as rapidly compared to those without it, so that at high NNAL levels, this SNP's protection disappears. Analyzing only adenocarcinomas, the effect of the variant was even stronger, with the risk of cancer increasing six times as fast. A common polymorphism of CYP1B1 may play a role in the risk of NNK, a powerful lung carcinogen, in the development of lung cancer in smokers.

Asthma, atopy, and lung function among racially diverse, poor inner-urban Minneapolis schoolchildren.

As part of an assessment of schoolchildren's environmental exposures and health, a probability sample of 136 children from diverse racial/ethnic backgrounds was drawn from grades 2-5 of two inner-urban Minneapolis schools (Whittier, Lyndale). Questionnaires were administered to a parent/guardian; blood samples for IgE and lung function tests were obtained. Overall adjusted rates for lifetime asthma (15.4%; 95%CI 9.3-21.5%), asthma in the last 12 months (13.6%; 7.8-19.4%), and current asthma medication use (10.5%; 5.3-15.7%) were higher than reported US national rates. Adjusted rates for lifetime physician-diagnosed asthma differed significantly among racial/ethnic groups (P<0.01): African-Americans (25.9%), White/Others (25.8%), Hispanics (9.3%), Somalis (1.8%), Asians (0%). Corresponding rates for atopy (total IgE>100 IU/mL or an allergen-specific IgE>0.35 IU/mL) were: African-Americans (66.6%), White/Others (100%), Hispanics (77.2%), Somalis (78.1%), Asians (81.8%). Lung function (FEV1, FVC) was analyzed by linear regression using log-transformed data: significant race-specific differences in lung function were found relative to White/Others (P<0.001 for each racial/ethnic group): African-Americans (FEV1 -16.5%, FVC -16.9%), Somalis (-22.7%, -26.8%), Hispanics (-12.2%, -11.4%) and Asians (-11.1%, -12.4%). Females had significantly lower FEV1 (-8.8%) and FVC (-11.0%) than males. An unexplained, significant difference in children's lung function was found between the two schools. A history of physician-diagnosed asthma was not associated with decreased lung function. Factors other than poverty, inner-urban living, and IgE levels (atopy) need to be considered in the development of childhood asthma.

Impact of training on work-related assault.

Although training is often recommended as a part of a comprehensive approach to address occupational violence, little empirical literature exists to support this recommendation. Over 40% of nurses responding to the Minnesota Nurses Study reported being trained about occupational violence, involving seven different training topics. Although at the univariate level, an increased risk was identified for nurses trained in managing assaultive/violent patients, no statistically significant results remained at the multivariate level. This lack of protection from training is consistent with previous research, although the explanations for this lack of effect remain unclear. Additional research is necessary to obtain more specific details on occupational violence training, including training content and methods, to understand more thoroughly the impact of training on occupational violence.

Risk factors for work-related assaults on nurses.

BACKGROUND: Work-related homicides have been the subject of considerable study, but little is known about nonfatal violence and relevant risk factors. METHODS: We surveyed 6300 Minnesota nurses who were selected randomly from the 1998 licensing database and determined their employment and occupational violence experience. In a nested case-control study, we examined environmental exposures and physical assault. Cases of assault in the previous 12 months and controls randomly selected from assault-free months were surveyed about prior-month exposures. RESULTS: After adjustment by multiple logistic regression, incidence of physical assault was 13.2 per 100 persons per year (95% confidence interval = 12.2-14.3). Among 310 cases and 946 control subjects, odds ratios for assault were increased: in nursing homes or long-term care facilities (2.6; 1.9-3.6), emergency departments (4.2; 1.3-12.8), and psychiatric departments (2.0; 1.1-3.7); in environments not "bright as daylight" (2.2; 1.6-2.8); and for each additional hour of shift duration (1.05; 0.99-1.11). Risks were decreased when carrying cellular telephones or personal alarms (0.3; 0.2-0.7). CONCLUSIONS: These results may guide in-depth investigation of ways protective and risk factors can control violence against nurses.