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Background: Educational attainment is a social determinant of health and frequently used as an indicator of socioeconomic status. Educational attainment is a predictor of cancer mortality, but associations with site-specific cancer incidence are variable. The aim of this study was to evaluate the association of educational attainment and site-specific cancer incidence adjusting for known risk factors in a large prospective cohort., Methods: Men and women enrolled in the American Cancer Society's Cancer Prevention Study-II Nutrition Cohort who were cancer free at baseline were included in this study (n = 148,965). Between 1992 and 2017, 22,810 men and 17,556 women were diagnosed with incident cancer. Cox proportional hazards regression models were used to estimate age- and multivariable-adjusted risk and 95% confidence intervals of total and site-specific cancer incidence in persons with lower versus higher educational attainment., Results: Educational attainment was inversely associated with age-adjusted cancer incidence among men but not women. For specific cancer sites, the multivariable-adjusted risk of cancer in the least versus most educated individuals remained significant for colon, rectum, and lung cancer among men and lung and breast cancer among women., Conclusions: Educational attainment is associated with overall and site-specific cancer risk though adjusting for cancer risk factors attenuates the association for most cancer sites., Impact: This study provides further evidence that educational attainment is an important social determinant of cancer but that its effects are driven by associated behavioral risk factors suggesting that targeting interventions toward those with lower educational attainment is an important policy consideration., (©2023 American Association for Cancer Research.)

New guidelines for Cancer Center Support Grants have recently been issued by the NCI that require increased attention to cancer center catchment areas and their community outreach and engagement activities [PAR-21-321]. Past experience with these requirements has engendered some confusion and frustration on the part of both researchers and reviewers that these new guidelines aim to dispel. In this commentary we, as experienced cancer center leaders in population sciences, offer our views on the most important aspects of the new guidelines and provide three examples of the kinds of programs that can apply cancer prevention and control research to improve cancer population health. With 71 NCI-Designated Cancer Centers in 36 states, the potential for broad impact on the reduction of the nation's cancer burden is enormous if the intended application of cancer center research to individuals and populations is fulfilled., (©2022 American Association for Cancer Research.)

Background: East Africa is affected by a disproportionately high burden of esophageal squamous cell carcinoma (ESCC)., Methods: We conducted an incident case-control study in Dar es Salaam, Tanzania with 1:1 matching for gender and age. A questionnaire evaluated known and putative risk factors for ESCC. Cochran-Mantel-Haenszel and multivariable conditional logistic regression analyses were applied to evaluate associations with ESCC risk, with adjustment for geographic zone., Results: Of 471 cases and 471 controls, the majority were male (69%); median ages were 59 and 55, respectively. In a multivariable logistic regression model, a low International Wealth Index (IWI) score [OR 2.57; 95% confidence interval (CI), 1.41-4.68], former smoking (OR 2.45; 95% CI, 1.46-4.13), second-hand smoke in the household (OR 1.67; 95% CI, 1.01-2.77), daily spicy chilies (OR 1.62; 1.04-2.52), and daily salted foods (OR 2.02; 95% CI, 1.06-3.85) were associated with increased risk of ESCC. Daily consumption of raw greens (OR 0.36; 95% CI, 0.16-0.80), fruit (OR 0.47; 95% CI, 0.27-0.82), and smoked fish (OR 0.31; 95% CI, 0.15-0.66) were protective. Permanent residence in the Central (OR 5.03; 95% CI, 2.16-11.73), Northern-Lake (OR 2.40; 95% CI, 1.46-3.94), or Southern Highlands zones (OR 3.18; 95% CI, 1.56-6.50) of Tanzania were associated with increased risk compared with residence in the Eastern zone., Conclusions: Low IWI score, smoke exposure(s), geographic zone, and dietary factors were associated with risk for ESCC in Tanzania., Impact: These findings will inform the development of future hypothesis-driven studies to examine risk factors for the high burden of ESCC in East Africa. See related commentary by McCormack et al., p. 248 ., (©2020 American Association for Cancer Research.)

Background: The etiology of breast cancer is a complex system of interacting factors from multiple domains. New knowledge about breast cancer etiology continues to be produced by the research community, and the communication of this knowledge to other researchers, practitioners, decision makers, and the public is a challenge., Methods: We updated the previously published Paradigm model (PMID: 25017248) to create a framework that describes breast cancer etiology in four overlapping domains of biologic, behavioral, environmental, and social determinants. This new Paradigm II conceptual model was part of a larger modeling effort that included input from multiple experts in fields from genetics to sociology, taking a team and transdisciplinary approach to the common problem of describing breast cancer etiology for the population of California women in 2010. Recent literature was reviewed with an emphasis on systematic reviews when available and larger epidemiologic studies when they were not. Environmental chemicals with strong animal data on etiology were also included., Results: The resulting model illustrates factors with their strength of association and the quality of the available data. The published evidence supporting each relationship is made available herein, and also in an online dynamic model that allows for manipulation of individual factors leading to breast cancer (https://cbcrp.org/causes/)., Conclusions: The Paradigm II model illustrates known etiologic factors in breast cancer, as well as gaps in knowledge and areas where better quality data are needed., Impact: The Paradigm II model can be a stimulus for further research and for better understanding of breast cancer etiology., (©2020 American Association for Cancer Research.)

Background: This study uses a novel geographic approach to summarize the distribution of breast cancer in San Francisco and aims to identify the neighborhoods and racial/ethnic groups that are disproportionately affected by this disease., Methods: Nine geographic groupings were newly defined on the basis of racial/ethnic composition and neighborhood socioeconomic status. Distribution of breast cancer cases from the Greater Bay Area Cancer Registry in these zones were examined. Multivariable logistic regression models were used to determine neighborhood associations with stage IIB + breast cancer at diagnosis. Cox proportional hazards regression was used to estimate the hazard ratios for all-cause and breast cancer-specific mortality., Results: A total of 5,595 invasive primary breast cancers were diagnosed between January 1, 2006 and December 31, 2015. We found neighborhood and racial/ethnic differences in stage of diagnosis, molecular subtype, survival, and mortality. Patients in the Southeast (Bayview/Hunter's Point) and Northeast (Downtown, Civic Center, Chinatown, Nob Hill, Western Addition) areas were more likely to have stage IIB + breast cancer at diagnosis, and those in the East (North Beach, Financial District, South of Market, Mission Bay, Potrero Hill) and Southeast were more likely to be diagnosed with triple-negative breast cancers (TNBC). Compared with other racial/ethnic groups, Blacks/African Americans (B/AA) experienced the greatest disparities in breast cancer-related outcomes across geographic areas., Conclusions: San Francisco neighborhoods with lower socioeconomic status and larger minority populations experience worse breast cancer outcomes., Impact: Our findings, which reveal breast cancer disparities at sub-county geographic levels, have implications for population-level health interventions., (©2019 American Association for Cancer Research.)

Background: Mammographic breast density declines during menopause. We assessed changes in volumetric breast density across the menopausal transition and factors that influence these changes., Methods: Women without a history of breast cancer, who had full field digital mammograms during both pre- and postmenopausal periods, at least 2 years apart, were sampled from four facilities within the San Francisco Mammography Registry from 2007 to 2013. Dense breast volume (DV) was assessed using Volpara on mammograms across the time period. Annualized change in DV from pre- to postmenopause was estimated using linear mixed models adjusted for covariates and per-woman random effects. Multiplicative interactions were evaluated between premenopausal risk factors and time to determine whether these covariates modified the annualized changes., Results: Among the 2,586 eligible women, 1,802 had one premenopausal and one postmenopausal mammogram, 628 had an additional perimenopausal mammogram, and 156 had two perimenopausal mammograms. Women experienced an annualized decrease in DV [-2.2 cm 3 (95% confidence interval, -2.7 to -1.7)] over the menopausal transition. Declines were greater among women with a premenopausal DV above the median (54 cm 3 ) versus below (DV, -3.5 cm 3 vs. -1.0 cm 3 ; P < 0.0001). Other breast cancer risk factors, including race, body mass index, family history, alcohol, and postmenopausal hormone therapy, had no effect on change in DV over the menopausal transition., Conclusions: High premenopausal DV was a strong predictor of greater reductions in DV across the menopausal transition., Impact: We found that few factors other than premenopausal density influence changes in DV across the menopausal transition, limiting targeted prevention efforts., (©2019 American Association for Cancer Research.)

Background: Higher socioeconomic position (SEP) has been associated with increased risk of breast cancer. Its relationship with earlier age of pubertal onset, a risk factor for breast cancer, is less clear. Methods: We studied the relationship of SEP to pubertal onset in a multiethnic cohort of 1,237 girls ages 6 to 8 years at baseline. Girls in three U.S. cities were followed for 5 to 8 years with annual clinical examinations from 2004 to 2012. SEP measures were examined for associations with pubertal onset, assessed by breast budding (thelarche) and pubic hair development (adrenarche). Analyses were conducted with accelerated failure time models using a Weibull distribution, with left, right, and interval censoring. Results: Higher body mass index percentage at entry to the study and black or Hispanic race/ethnicity were the strongest predictors of age at pubertal onset. An SEP index comprising household family income, mother's education, and home ownership was an independent predictor of thelarche in adjusted models for all girls together and for white and Latina, separately, but not black girls, and the relationship varied by study site. The SEP index was not related to adrenarche in adjusted models. Overall, girls from the lowest quintile of SEP entered puberty on average 6% earlier than girls from the highest quintile (time ratio = 0.94; 95% confidence interval 0.91-0.97) in adjusted models. Conclusions: Our results suggest that early-life SEP may influence the timing of pubertal development. Impact: Factors related to lower SEP in childhood can adversely affect early development in ways that may increase the risk of breast cancer. Cancer Epidemiol Biomarkers Prev; 26(12); 1714-21. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Cancer control science has been evolving since it first became a focus for cancer research and program activities a century ago. The evolution of the field has responded to historical megatrends along the way that keep it relevant to the cancer-related needs of society. This commentary describes some of the key trends and developments now influencing cancer control and population sciences that reflect societal change and new tools and concepts in modern biomedical science. New directions include the impact of climate change, health care delivery research, the growth of population health science, data science, precision medicine, data sharing, implementation science, and new technologies, including social media and new geospatial methodologies. Cancer Epidemiol Biomarkers Prev; 26(8); 1165-9. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Background: Breast cancer has a complex etiology that includes genetic, biologic, behavioral, environmental, and social factors. Etiologic factors are frequently studied in isolation with adjustment for confounding, mediating, and moderating effects of other factors. A complex systems model approach may present a more comprehensive picture of the multifactorial etiology of breast cancer., Methods: We took a transdisciplinary approach with experts from relevant fields to develop a conceptual model of the etiology of postmenopausal breast cancer. The model incorporated evidence of both the strength of association and the quality of the evidence. We operationalized this conceptual model through a mathematical simulation model with a subset of variables, namely, age, race/ethnicity, age at menarche, age at first birth, age at menopause, obesity, alcohol consumption, income, tobacco use, use of hormone therapy (HT), and BRCA1/2 genotype., Results: In simulating incidence for California in 2000, the separate impact of individual variables was modest, but reduction in HT, increase in the age at menarche, and to a lesser extent reduction in excess BMI >30 kg/m(2) were more substantial., Conclusions: Complex systems models can yield new insights on the etiologic factors involved in postmenopausal breast cancer. Modification of factors at a population level may only modestly affect risk estimates, while still having an important impact on the absolute number of women affected., Impact: This novel effort highlighted the complexity of breast cancer etiology, revealed areas of challenge in the methodology of developing complex systems models, and suggested additional areas for further study., (©2014 American Association for Cancer Research.)

In 2012, the National Cancer Institute (NCI) engaged the scientific community to provide a vision for cancer epidemiology in the 21st century. Eight overarching thematic recommendations, with proposed corresponding actions for consideration by funding agencies, professional societies, and the research community emerged from the collective intellectual discourse. The themes are (i) extending the reach of epidemiology beyond discovery and etiologic research to include multilevel analysis, intervention evaluation, implementation, and outcomes research; (ii) transforming the practice of epidemiology by moving toward more access and sharing of protocols, data, metadata, and specimens to foster collaboration, to ensure reproducibility and replication, and accelerate translation; (iii) expanding cohort studies to collect exposure, clinical, and other information across the life course and examining multiple health-related endpoints; (iv) developing and validating reliable methods and technologies to quantify exposures and outcomes on a massive scale, and to assess concomitantly the role of multiple factors in complex diseases; (v) integrating "big data" science into the practice of epidemiology; (vi) expanding knowledge integration to drive research, policy, and practice; (vii) transforming training of 21st century epidemiologists to address interdisciplinary and translational research; and (viii) optimizing the use of resources and infrastructure for epidemiologic studies. These recommendations can transform cancer epidemiology and the field of epidemiology, in general, by enhancing transparency, interdisciplinary collaboration, and strategic applications of new technologies. They should lay a strong scientific foundation for accelerated translation of scientific discoveries into individual and population health benefits.

Background: Little is known about the long-term impact of comorbidity among women with breast cancer., Methods: We studied a prospective cohort of 2,272 women with breast cancer, who were recruited following initial breast cancer treatment. Associations of the Charlson comorbidity index (CCI) and hypertension with survival were evaluated in delayed entry Cox proportional hazards models., Results: During a median follow-up of nine years, higher CCI scores were independently associated with an increased risk of death from all causes [HR, 1.32; 95% confidence interval (CI), 1.13-1.54] and from nonbreast cancer causes (HR, 1.55; 95% CI, 1.19-2.02), but not from breast cancer (HR, 1.14; 95% CI, 0.93-1.41). Hypertension was independently associated with an increased risk of death from all causes (HR, 1.55; 95% CI, 1.20-1.99), from nonbreast cancer causes (HR, 1.67; 95% CI, 1.10-2.54), and from breast cancer (HR, 1.47; 95% CI, 1.03-2.09), but these associations were no longer significant after adjustment for antihypertensive medication. The relationship between the CCI and overall survival was the strongest among women with stage I disease (stage I, HR, 1.65; 95% CI, 1.26-2.16 vs. stage III, HR, 0.53; 95% CI, 0.23-1.25)., Conclusion: The CCI was independently associated with lower overall and nonbreast cancer survival, but not with breast cancer-specific survival., Impact: Comorbidity may play an important role in breast cancer outcomes., (©2012 AACR)

Objective: To report on the effect of the Breast and Cervical Cancer Intervention Study (BACCIS), a multicomponent intervention conducted in the San Francisco Bay Area between 1992 and 1997., Methods: BACCIS targeted approximately 25,000 multiethnic, underserved women in eight neighborhoods and the public health clinics that served them. An outreach intervention using lay health worker peers and clinic provider inreach intervention to improve breast and cervical cancer screening were evaluated in a quasi-experimental, controlled trial with pretest and posttest household surveys of 1,599 and 1,616 women, respectively. Surveys were conducted in English, Spanish, Mandarin, and Cantonese., Results: Analyses of community survey results showed no significant improvement in reported screening behaviors. Reports of mammography in the intervention areas in the previous 2 years, or for Pap smear in the previous 3 years, did not differ significantly (73-71% and 84-87%, respectively, for pretest and posttest surveys)., Conclusion: High baseline screening rates, lack of sensitive measures of change at the population level, contamination of the control group, and an imbalance of predictive factors at baseline contributed to the difficulty of assessing the value of the intervention. Lessons learned from this inconclusive study may be of value to future community intervention studies of cancer screening and other health behaviors in multiethnic underserved urban populations.

Four phases in the evolution of cancer control frameworks are reviewed, highlighting how national Canadian and United States planning and implementation activities have built on each other's work to define and guide cancer control research. Hallmarks have come to be: (a) coordination of the cycle that applies research to practice and policy decisions; (b) synthesis of knowledge at each phase of cancer control framework; (c) a focus on populations and public health with feedback loops between fundamental and applied research; and (d) interdisciplinary integration of the biological, behavioral, social, and other population sciences. Current research priorities and initiatives based on the research framework now common to both Canada and the United States are described. We conclude by calling for an international forum for the systematic advancement of cancer control research, and closer ties between the cancer control communities in North America.

Low-income women are at high risk of developing cervical cancer attributable not only to the higher prevalence of risk factors in this population but also to the lack of timely follow-up of abnormal Pap smears. This study evaluates the efficacy of an aggressive follow-up strategy. Women with abnormal Pap smear results after screening in a public hospital emergency department were randomly assigned to follow-up either by a case-managed approach using computerized tracking and universal colposcopy or by traditional care. The main outcome was the proportion of women receiving follow-up in 6 months. A secondary outcome was the proportion of women receiving follow-up by 6 months and diagnostic resolution in 18 months. Of 54 women in the intervention group, 65% kept at least one follow-up appointment in 6 months compared with 41% of the 54 women in the control group (P = 0.012). Half the women in the intervention group versus 19% of women in the control group had follow-up in 6 months and diagnostic resolution in 18 months (P = 0.001). After adjusting for age, initial Pap smear result, and race/ethnicity, the odds of having follow-up in 6 months were four times greater for women in the intervention group (odds ratio = 4.0; 95% confidence interval, 1.6-9.7), and the odds of having both follow-up in 6 months and diagnostic resolution in 18 months were more than six times greater (odds ratio = 6.5; 95% confidence interval, 2.4-17.8). This study demonstrates that an aggressive follow-up strategy significantly improves the rate of both initial follow-up and diagnostic resolution of abnormal Pap smears among low-income women with atypical squamous cells of undetermined significance and atypical glandular cells of undetermined significance when compared with traditional care.

A nested case-control study was conducted to investigate the hypothesis that women with high levels of high-density lipoprotein cholesterol (HDL-C) are at an increased risk of breast cancer. The source population was a cohort of 95,000 women enrolled in the Kaiser Permanente Medical Care Program who underwent a routine multiphasic health examination between 1964 and 1971. From the more than 2,000 breast cancer cases diagnosed in this cohort, 200 cases were randomly selected for this study. For each case, one control who matched on age and date of examination was chosen. Lipid and lipoprotein levels were measured in archived serum samples collected at the time of the women's examinations. Breast cancer risk factor information was obtained from questionnaires completed by the women when their blood was drawn and was supplemented with information from medical records. HDL-C levels were not significantly different between the cases and controls overall; however, a statistically significant interaction between the HDL-C level and menopausal status at diagnosis was detected. Premenopausal cases had mean HDL-C levels 3.48 mg/dl lower than matched controls [95% confidence interval (CI), -7.05, 0.09], whereas postmenopausal cases had levels 2.05 mg/dl higher than controls (95% CI, -0.94, 5.03). In multivariate conditional logistic regression analyses, the odds ratio associated with each 1 mg/dl increase in HDL-C was 0.96 (95% Cl, 0.93-1.0) for premenopausal women and 1.02 (95% CI, 0.99-1.05) for postmenopausal women. Although many breast cancer risk factors are associated with high HDL-C, the relationship between breast cancer and HDL-C was independent of other factors evaluated.

To assess whether Helicobacter pylori-related inflammation increases oxidative DNA damage, we evaluated the association between H. pylori infection and urinary excretion of an adduct of oxidative DNA damage, 8-hydroxy-2-deoxyguanosine (8ohdG). Subjects included 555 healthy persons, ages 20-39, within the Kaiser Permanente Medical Care Program in Northern California. We tested sera for antibodies to H. pylori by ELISA; collected demographic, dietary, smoking, and alcohol data by questionnaire; and assayed 24-h urine samples for 8ohdG with a newly developed ELISA kit. Two hundred eighty-one subjects provided adequate 24-h urine samples for 8ohdG and creatinine assays and had detectable levels of 8ohdG. After adjusting for 24-h urinary creatinine (Ucr) and demographic factors, persons without H. pylori infection had significantly higher amounts of 24-h urinary 8ohdG than infected persons (geometric mean, 18.04 microg 8ohdG/Ucr g versus 14.36 microg 8ohdG/Ucr g, respectively; P = 0.008). Excretion of 8ohdG was higher in whites and Hispanics (17.44 and 18.09 microl/Ucr g) than in blacks (13.21 microg/Ucr g; P < 0.001). Gender was not significantly associated with 8ohdG excretion (16.18 microg/Ucr g for males versus 16.01 microg/Ucr g for females; P = 0.883). Of the dietary factors evaluated, vitamin C negatively correlated (P < 0.001) and carbohydrate intake positively correlated with 8ohdG excretion (P = 0.003). Infection with H. pylori was strongly associated with decreased 8ohdG excretion in the urine. This unexpected finding suggests either that DNA repair is deficient in infected subjects, that inflammation destroys the adduct, or that urinary 8ohdG is not an accurate measure of gastric damage.

Phytoestrogens include several classes of chemical compounds (i.e., isoflavones, coumestans, and lignans) which are structurally similar to endogenous estrogens. In biological systems, they have both estrogenic and antiestrogenic effects and may reduce the risk of developing certain types of hormonally related diseases. However, little information is available on population differences in exposure to phytoestrogens. To examine racial/ethnic differences in urinary phytoestrogen levels, 50 young women (ages 20-40 years) were randomly selected from participants in a previous epidemiological study in which 24-h urine specimens and a dietary assessment were obtained. Subjects were members of the Kaiser Permanente Medical Care Program of northern California. Selection was stratified on race/ethnicity. Urinary levels of seven phytoestrogens were measured using high-performance liquid chromatography-mass spectrometry. Substantial variation in phytoestrogen levels was observed and racial/ethnic differences are described. The highest levels of coumestrol and the lignans were observed in white women and the lowest levels in Latina and African American women. Genistein levels, however, were highest in Latina women; other isoflavone levels did not differ significantly by race/ethnicity.

In a case-control study of urinalysis screening in the prevention of death from bladder cancer, hematuria was present in a higher proportion of cases than controls as long as five or six years before the diagnostic evaluation that led to the diagnosis of bladder cancer. In a separate cohort study data base that permitted the follow-up of 1046 persons with a physician's diagnosis of hematuria, 11 cases of bladder cancer were diagnosed more than two (mean 7.4) years after the hematuria diagnosis (4.3 cases expected; age-sex standardized morbidity ratio, 2.5; 95% confidence interval, 1.3-4.5). Bladder cancer was ruled out initially by cystoscopy in 8 of the 11 cases. Although we cannot be certain that preexisting bladder cancer or bladder cancer risk factors did not cause the bleeding, we hypothesize that hematuria can be a predictor as well as a manifestation of bladder cancer, based on a tendency for bladder mucosa with premalignant changes to bleed. The implications for screening and clinical practice remain to be determined.

Screening urine for microhematuria as an indicator of serious disease is controversial because of the low positive predictive value of such screening and the costs and risks of the associated evaluation. To further evaluate test properties, we retrospectively examined the outcomes of 20,571 men aged > or = 35 years and women aged > or = 55 years who voluntarily had a Personal Health Appraisal in 1980 as members of a large prepaid health plan. Hematuria was detected by dipstick in 876 cases (4.3%); 278 were excluded because of evidence of previous urological disease which could cause hematuria. Review of the medical records of 598 patients with asymptomatic microhematuria as shown by a positive dipstick result indicated that 99% had a follow-up evaluation within 3 months of positive test results for hematuria and had various levels of urological evaluation thereafter. However, urological cancers (2 prostate, 1 bladder) developed in only 3 patients within the next 3 years. On the basis of San Francisco-Oakland Surveillance, Epidemiology, and End Results program data, rates of urological cancer were evaluated among patients whose test results were negative for hematuria, and these cancer rates were found to be almost the same as the rate among patients with asymptomatic microhematuria. Sensitivity of a single dipstick urinalysis result using microhematuria to indicate urological cancer within 3 years was 2.9%; specificity was 96.7%; and positive predictive value was 0.5%. Multivariate analysis which adjusted for age, gender, and race showed that the relative risk of 2.1 (95% confidence interval, 0.7-6.6) for urological cancer was not significantly elevated among patients with asymptomatic microhematuria compared with patients who had negative test results. These findings based on a single test are consistent with the current lack of recommendations for screening for microhematuria among asymptomatic adults.

Erythrocytes containing micronuclei serve as an indicator of genotoxic exposure in splenectomized individuals. Micronucleated erythrocytes, derived from cytogenetically damaged RBC precursors, are not selectively removed from peripheral blood in individuals who lack splenic function. The relationship between micronucleated cell frequencies and demographic, environmental, and dietary factors was examined in 44 subjects with previous splenectomy due to trauma. Their micronucleated cell counts fit a log-normal distribution, with geometric means of 3.3 micronucleus-containing cells/1000 reticulocytes and 2.7/1000 normochromatic erythrocytes. A multiple regression analysis showed that drinking five cups of coffee or tea/day (relative to none) was associated with an approximately 2-fold higher frequency of micronucleated cells. Weaker statistical associations were also noted with micronucleus frequency and the consumption of calcium supplements (associated with a higher frequency) and vitamins A, C, or E (lower frequency). An apparent trend of higher micronucleus counts with age was attenuated when other factors were considered in the regression. Cigarette smoking and decaffeinated coffee consumption were among the factors not associated with elevated micronucleated cell frequencies. Because the occurrence of micronuclei in reticulocytes reflects cytotoxic exposures within the past 3-8 days, it may be possible to test directly the relationship of these factors to micronucleus formation through intervention studies.

Barbiturate exposure during childhood was assessed from medical records of 237 children with intracranial and spinal cord tumors and 474 matched controls in a prepaid health plan. In utero exposure was also examined in a subset of 86 "cases" and 172 controls whose mothers were health plan members during pregnancy. No association of in utero exposure to barbiturates was found [odds ratio (O.R.) = 0.96, 95% confidence interval (C.I.) = 0.47, 1.94]. An association was noted for barbiturate use during childhood (O.R. = 1.80, 95% C.I. = 1.18, 2.74) but was reduced (O.R. = 1.41, 95% C.I. = 0.89, 2.21) when history of epilepsy was taken into account and was no longer significant. An apparent dose-response effect disappeared after adjustment for a history of epilepsy. Although barbiturate use for epilepsy due to preexisting brain tumors clearly explains some of the observed association, the small, residual risk prevents us from ruling out a possible carcinogenic effect of barbiturates. Further study of cohorts of adult as well as childhood users of barbiturates and other anticonvulsants is recommended.

We examined breast cancer incidence in a cohort of about 69,000 women who were members of a large prepaid health plan in Northern California and who answered detailed questions about alcohol consumption from 1979 through 1984 as part of a voluntary multiphasic health checkup. Among white, black, and Hispanic women with no prior cancer, breast cancer had developed in 303 by the end of 1984. In analysis controlling only for age there was a progressive increase in breast cancer incidence with each higher level of reported alcohol consumption. In multivariate analyses controlled for age, race, body mass, and smoking, the relative risk at 1-2 drinks per day was 1.5 [95% confidence interval (CI) 1.0-2.3], at 3-5 drinks per day it was 1.5 (95% CI 0.8-2.8), and at 6 or more drinks per day it was 3.3 (95% CI 1.2-9.3). Past drinkers tended to have been heavier drinkers than current drinkers and had a relative risk of 2.2 (95% CI 1.2-3.9). Study of wine, beer, and liquor use did not suggest that any particular alcoholic beverage was responsible. Significant associations with heavy alcohol consumption were strongest among white, and among postmenopausal women. This study adds support to the growing evidence that alcohol may be a risk factor for development of breast cancer.

We examined the hypothesis that low levels of serum uric acid are associated with elevated cancer risk. A subpopulation (163,830 members) of a large health maintenance organization was followed for a mean of 9.8 years after a multiphasic health checkup at which serum uric acid level was measured. Total cancer incidence as well as site-specific incidence (for lung, colon, and prostate cancer in men and lung, colon, breast, uterine, and cervical cancer in women) was ascertained from hospital discharge records and the Surveillance, Epidemiology and End Results program in the San Francisco-Oakland Bay area. Age-adjusted cancer incidence was not elevated in the lower deciles of serum uric acid level. After adjusting for age, race, education, smoking, alcohol consumption, and body mass, using proportional hazards models, the risk of cancer was not elevated at lower levels of uric acid. Our results suggest that if increased risk of cancer is associated with low serum uric acid, this risk is associated with serum uric levels below those commonly seen in human populations.