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We investigated whether in utero exposure to maternal pregravid obesity and/or gestational diabetes mellitus (GDM) was associated with early puberty in girls. We used data from a longitudinal study of 421 mother-daughter pairs enrolled in an integrated health services organization, Kaiser Permanente Northern California (2005-2012). Girls aged 6-8 years were followed annually through ages 12-14 years. Onset of puberty was assessed using study clinic-based Tanner staging. We examined associations of self-reported pregravid obesity and maternal GDM with timing of the daughter's transition to pubertal maturation stage 2 or above for development of breasts and pubic hair, using accelerated failure time regression models with interval censoring to estimate time ratios and hazard ratios and corresponding 95% confidence intervals. Maternal obesity (pregravid body mass index (BMI; weight (kg)/height (m)(2)) ≥30) was associated with a daughter's earlier transition to breast and pubic hair stage 2+ in comparison with girls whose mothers had pregravid BMI <25. These associations were attenuated and not statistically significant after adjustment for covariates. Girls whose mothers had both pregravid BMI ≥25 and GDM were at higher risk of an earlier transition to pubic hair stage 2+ than those whose mothers had neither condition (adjusted time ratio = 0.89, 95% confidence interval: 0.83, 0.96; hazard ratio = 2.97, 95% confidence interval: 1.52, 5.83). These findings suggest that exposure to maternal obesity and hyperglycemia places girls at higher risk of earlier pubarche., (© The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The concept of translational cancer epidemiology has evolved since its early beginnings in 1937 with the establishment of the National Cancer Institute. Conceptual models of cancer control research have also evolved over the last 30 years, to the point where we now have 4 stages of translational research (T0-T4). The current review by Lam et al. (Am J Epidemiol. 2015;181(7):451-458) covers cancer epidemiology research supported by the National Cancer Institute and a selected sample of the cancer epidemiology literature. It suggests that most cancer epidemiology in the last 10 years has been in pure discovery research. Current "drivers" of cancer epidemiology research, including new technologies, team science multilevel research, and knowledge integration, are not strongly represented in the review. However, the use of epidemiology in the latter stages of translation may not have been captured by the scope of this review. The closer epidemiologists get to advanced stages of translation, the more likely they are to work with investigators in other disciplines in other sectors of society. An argument can be made that regardless of whether this kind of research is not happening or was just missed by the current review, the field of cancer epidemiology can expand its scope and further evolve towards more effective applications in population health., (© The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Epidemiology is at the center of translational science. Uniquely among biomedical disciplines, the methods and perspective of epidemiology span research from discovery to effective interventions and ultimately to their dissemination and implementation. However, shorthand designations for various phases of translational science, such as "T1, T2, T3, and T4," may be proliferating past the level of their usefulness. It is worthwhile to reflect on the actual nature of the science undertaken by epidemiologists along the continuum of discovery to application. The new challenge for epidemiology is the integration of knowledge and effective interventions into various societal settings working with allied disciplines not necessarily in the biomedical domain to ensure that these interventions have their intended effects on individual and public health.

In a case-control study of 73 women with and 141 women without spontaneous abortion, the authors determined the activity of the three principal caffeine-metabolizing enzymes--cytochrome P-4501A2 (CYP1A2), xanthine oxidase, and N-acetyltransferase 2--by measuring levels of caffeine metabolites in urine. After examining the effect of enzyme activity and different levels of caffeine intake, they concluded that there was no evidence that an interaction between enzyme activity and caffeine intake during pregnancy resulted in risk of spontaneous abortion. In a subsample comparing 24 cases with recurrent (two or more) spontaneous abortions and 21 controls with two or more livebirths and no previous spontaneous abortions, the unadjusted odds ratio for low CYP1A2 enzyme activity (below the median) was 0.92 (95% confidence interval (CI) 0.28-3.04) compared with higher CYP1A2 activity. The odds ratio for risk of recurrent spontaneous abortion and low xanthine oxidase activity (below the median) versus higher activity was 0.37 (95% CI 0.10-1.29). Phenotypically slow acetylators (N-acetyltransferase 2 index <0.37) had an odds ratio of 1.58 (95% CI 0.48-5.13) for recurrent loss compared with rapid acetylators. Thus, some association of the latter two caffeine-metabolizing enzymes with recurrent spontaneous abortion is suggested but may also be due to chance.

Low protein diets are commonly prescribed for patients with idiopathic calcium nephrolithiasis, who account for > 80% of new diagnoses of kidney stones. This dietary advice is supported by metabolic studies and epidemiologic observational studies but has not been evaluated in a controlled trial. Using 1983-1985 data from three Northern California Kaiser Permanente Medical Centers, the authors randomly assigned 99 persons who had calcium oxalate stones for the first time to a low animal protein, high fiber diet that contained approximately 56-64 g daily of protein, 75 mg daily of purine (primarily from animal protein and legumes), one-fourth cup of wheat bran supplement, and fruits and vegetables. Intervention subjects were also instructed to drink six to eight glasses of liquid daily and to maintain adequate calcium intake from dairy products or calcium supplements. Control subjects were instructed only on fluid intake and adequate calcium intake. Both groups were followed regularly for up to 4.5 years with food frequency questionnaires, serum and urine chemistry analysis, and abdominal radiography; and they were urged to comply with dietary instructions. In the intervention group of 50 subjects, stones recurred in 12 (7.1 per 100 person-years) compared with two (1.2 per 100 person-years) in the control group; both groups received a mean of 3.4 person-years of follow-up (p = 0.006). After adjustment for possible confounding effects of age, sex, education, and baseline protein and fluid intake, the relative risk of a recurrent stone in the intervention group was 5.6 (95% confidence interval 1.2-26.1) compared with the control group. The authors conclude that advice to follow a low animal protein, high fiber, high fluid diet has no advantage over advice to increase fluid intake alone.

The relation of work-related psychologic stress to spontaneous abortion was examined in a prospective study of 3,953 pregnant, employed members of a prepaid health plan in California, recruited between 1990 and 1991. Information on occupation, psychologic stress-related factors at work, social support at work, physical exertion at work, life events, pregnancy worries, and potential confounders was obtained by a telephone interview. Psychologic job stress and social support at work were assessed using an abbreviated version of the instrument developed by Karasek and colleagues (Los Angeles: University of Southern California, 1986). Results from the multivariate model indicated that, overall, stressful work was not associated with an increased risk of spontaneous abortion. However, interactions were observed between stressful work and maternal age over 32 years (p = 0.04), cigarette smoking (p = 0.02), and primigravidity (p = 0.06). Relative to the odds ratio for stressful work in young, nonsmoking, multigravid women without a history of two or more spontaneous abortions, the odds ratios for spontaneous abortion given stressful work were higher by 2.45 (95% confidence interval (CI) 1.03-5.81) for older women, 2.96 (95% CI 1.16-7.52) for smokers, and 2.27 (95% CI 0.97-5.27) for primigravid women.

Diseases associated with Helicobacter pylori infection, such as peptic ulcer disease and gastric cancer, afflict men more frequently than women. No study, however, has demonstrated any difference in sex-specific rates of H. pylori infection. In a healthy population undergoing multiphasic health evaluations in 1992-1993 as members of the Kaiser Permanente Medical Care Program of Northern California, adults aged 20-39 years were screened for antibodies to H. pylori infection using a serum enzyme-linked immunosorbent assay and were surveyed with regard to their demographic characteristics and health practices. Among 556 African-American, Hispanic, and white men and women, male sex was a significant risk factor for infection. Other risk factors included African-American race and Hispanic ethnicity, increasing age, living with children, birth in a developing country, and lower levels of income and education. Men consistently had a higher prevalence of antibodies across all strata of race/ethnicity, age, education, and income, and in multivariate analysis male sex remained significantly associated with infection (odds ratio = 2.0, 95% confidence interval 1.2-3.1). African-American race, Hispanic ethnicity, increasing age, lower levels of education, and birth in a developing country were also associated with infection in multivariate analysis. Data from previously reported seroprevalence studies support a tendency for men to have a higher risk of infection. The higher prevalence of infection among young males as observed in Northern California may account in part for the increased incidence of H. pylori-related diseases among men in later decades of life.

The issue of risk of breast cancer subsequent to benign breast diseases (BBD) remains controversial. To determine whether this risk varies by histologic type of BBD, degree of atypia (as measured by the Black-Chabon method), age at BBD biopsy, or length of follow-up, the authors followed 2,731 women in the San Francisco Bay Area for an average of 16 years after their first occurrence of biopsy-proven BBD between 1948 and 1973. The cohort's age-adjusted rate of breast cancer was 1.8 times that of the general population (95% confidence interval (CI) 1.6-2.2). Among the different histologic types of BBD, rates were greatest for intraductal papilloma (rate ratio (RR) = 3.9, 95% CI 2.0-7.4) and adenosis (RR = 2.5, 95% CI 1.2-4.9). Rates were also significantly elevated for fibrocystic BBD (RR = 1.5, 95% CI 1.1-1.9). Risk increased directly with degree of atypia, rising from a rate ratio of 1.8 among women with Black-Chabon scores of 1 and 2 (95% CI 1.5-2.2) to 7.2 among women with a Black-Chabon score of 5 (95% CI 1.8-28.9). Among women with the higher-risk types of BBD, rate ratios increased with age at BBD biopsy and decreased with increasing length of cancer-free follow-up. These findings are interpreted in the light of possible biases affecting this and other studies and recent advances in knowledge regarding neoplastic lesions and breast cell kinetics.

The authors prospectively studied the incidence of cancers of the colon and rectum in 106,203 men and women, both white and black, who supplied data at northern California Kaiser Permanente facilities about use of alcoholic beverages in 1978-1984. Analysis controlling for age, sex, race, body mass index, coffee use, total serum cholesterol, and education showed a positive association of alcohol use to both types of cancer, which was stronger for rectal cancer (trend test, p = 0.03) than for colon cancer (trend test, p = 0.11). When persons with a daily intake of three or more drinks were compared with abstainers, relative risk for rectal cancer was 3.17 (95% confidence interval (CI): 1.05-9.57) and relative risk for colon cancer was 1.71 (95% CI: 0.92-3.19). Women with a daily intake of three or more drinks had a relative risk for colon cancer of 2.56 (95% CI: 1.03-6.40) compared with 1.16 (95% CI: 0.46-2.90) for men. Among drinkers, preference for wine, beer, or hard liquor had no significant independent relation to either type of cancer; those who preferred beer were at slightly greater risk of rectal cancer, but those who preferred wine were more likely to develop colon cancer. These data suggest that total alcohol use, but no one specific beverage type, is associated with increased risk of rectal cancer.

A case-control study of the relationship of serum cholesterol to large bowel cancer incidence was performed for 245 members of the Kaiser Permanente Medical Care Program in northern California. Five controls were obtained for each case, matched for age, sex, race, and time of examination. The mean serum cholesterol levels of cases were not significantly different from those of controls for all colorectal cancers, right-sided colon cancers, and left-sided colon cancers. Analysis by quartiles of serum cholesterol level suggested neither a direct nor an inverse relationship between serum cholesterol and large bowel cancer, and there was no evidence of a threshold value below which the risk of cancer increased. The study did not support the findings from other studies of an inverse relationship between serum cholesterol and large bowel cancer.

Recent case-control studies have suggested that alcohol consumption may be associated with breast cancer incidence. This report is a retrospective cohort study of over 95,000 women who were members of the Kaiser Foundation Health Plan of Northern California. The stated alcohol consumption of these women was recorded at a multiphasic screening examination taken from 1964 to 1972 prior to any diagnosis of breast cancer. The incidence of breast cancer in this cohort was greater for women who drank, and among these drinkers, incidence increased in an irregular trend with heavier alcohol consumption. Control for the effects of race, education, smoking, and reproductive variables related to breast cancer all but eliminated the overall increased relative risk of drinkers compared with that of nondrinkers. However, the relatively small group of women who stated that they had three or more alcoholic drinks per day (5.2 per cent of the total) had a significantly elevated relative risk of 1.4 (p = 0.035) compared with nondrinkers, despite control for all available confounding variables. No significant interaction effect of smoking and alcohol was found. Women who had less than three drinks per day had no increased relative risk over nondrinkers. The results of this study might be explained either by an unrecognized carcinogenic effect of alcohol on breast tissue or by the confounding effect of other factors associated with heavy alcohol use.

The rate of occurrence of stones of the urinary tract was assessed in a large population served by the Northern California Kaiser Foundation Health Plan. The study involved three separate groups. First, data were obtained by questionnaire from approximately 175,000 adults who took a multiphasic health checkup in the period 1964-1972; of these generally well adult members, 26.2/1000 persons (32.0/1000 men and 21.0/1000 women) reported having ever been told by a physician that they had a urinary tract stone. Second, data were obtained from 139,000 persons served by the San Francisco outpatient facility in 1970-1972; 1.22/1000 per year (1.81/1000 men and 0.59/1000 women) had an initial diagnosis of a "new or recurrent" stone of the upper urinary tract. The third set of data was procured from the entire Northern California region in 1971-1975; 0.36/1000 (0.52/1000 men and 0.19/1000 women) were discharged from a hospital each year with a diagnosis of upper urinary tract stone. All rates were age-adjusted to the 1960 US Census population. Of these three rates, the rate derived from the outpatient visit record most closely estimates incidence, since nearly all persons who are hospitalized are first seen as outpatients. Rates of kidney stone diagnosis were three times more common in men and, although rare before 20 years of age, the frequency increased rapidly and peaked in the age group 40 to 59 years. Rates were approximately twice as high in whites as in blacks and Orientals; the frequency of stones was inversely related to socioeconomic status as measured by level of education. Over 90% of stones occurred in the upper urinary tract, and the majority contained calcium oxalate. Population-based rates of occurrence of kidney stones are not generally available in the United States. Comparisons with the few available studies indicate that rates in the Kaiser Foundation Health Plan population may be high.