Matthew P. Longnecker

Alcoholic beverage consumption in relation to risk of breast cancer: meta-analysis and review

The objective was to evaluate the association between alcohol consumption and risk of breast cancer. Data from 38 epidemiologic studies on alcohol consumption in relation to risk of breast cancer in women were included in a meta-analysis. A qualitative literature review also was conducted. The results showed strong evidence of a dose-response relation; however, the slope of the dose-response curve was quite modest. For example, daily consumption of one alcoholic drink was associated with an 11 percent increase (95 percent confidence interval, seven to 16 percent) in the risk of breast cancer compared with nondrinkers. An explanation for the marked variation in results across studies was not found. The modest size of the association and variation in results across studies leave the causal role of alcohol in question. The evidence that alcohol consumption affects the risk of breast cancer, however, appears to be growing stronger.

Meta-analysis of epidemiologic dose-response data.

We discuss methods for summarizing epidemiologic studies of dose-response. The data from such a study typically appear as a series of dose-specific relative risks, with one category serving as the common reference group. We present methods for estimating the dose-response parameters from single and multiple study reports, for assigning levels to exposure categories when modeling relative risks, and for investigating the effects of study design and subject characteristics on dose-response curves. Finally, we discuss the choice of fixed vs random effects models. We illustrate our points with data from case-control studies of the relation between duration of oral contraceptive use and risk of breast cancer.

Fish intake during pregnancy and early cognitive development of offspring

Background: Fish is a source of many nutrients that can be beneficial during pregnancy, as well as a source of neurotoxicant contaminants such as methylmercury. Previous investigations of fish intake in relation to neurodevelopment have focused on possible damage from contaminants, whereas potential benefits of fish consumption have been relatively unexplored Methods: We evaluated the association between maternal fish intake during pregnancy and offsprings early development of language and communication skills in a cohort of 7421 British children born in 1991–1992. Fish intake by the mother and child was measured by questionnaire. The childs cognitive development was assessed using adaptations of the MacArthur Communicative Development Inventory at 15 months of age and the Denver Developmental Screening Test at 18 months of age. Mercury was measured in umbilical cord tissue for a subset of 1054 children Results: Total mercury concentrations were low and were not associated with neurodevelopment. Fish intake by the mother during pregnancy, and by the infant postnatally, was associated with higher mean developmental scores. For example, the adjusted mean MacArthur comprehension score for children whose mothers consumed fish 4 or more times per week was 72 (95% confidence interval = 71–74), compared with 68 (66–71) among those whose mothers did not consume fish. Conclusions: When fish is not contaminated, moderate fish intake during pregnancy and infancy may benefit development.

Urinary metabolite concentrations of organophosphorous pesticides, bisphenol A, and phthalates among pregnant women in Rotterdam, the Netherlands : The Generation R study

Concern about potential health impacts of low-level exposures to organophosphorus (OP) pesticides, bisphenol A (BPA), and phthalates among the general population is increasing. We measured levels of six dialkyl phosphate (DAP) metabolites of OP pesticides, a chlorpyrifos-specific metabolite (3,5,6-trichloro-2-pyridinol, TCPy), BPA, and 14 phthalate metabolites in urine samples of 100 pregnant women from the Generation R study, the Netherlands. The unadjusted and creatinine-adjusted concentrations were reported, and compared to National Health and Nutrition Examination Survey and other studies. In general, these metabolites were detectable in the urine of the women from the Generation R study and compared with other groups, they had relatively high-level exposures to OP pesticides and several phthalates but similar exposure to BPA. The median concentrations of total dimethyl (DM) metabolites was 264.0 n mol/g creatinine (Cr) and of total DAP was 316.0 n mol/g Cr. The median concentration of mono-ethyl phthalate (MEP) was 222.0 microg/g Cr; the median concentrations of mono-isobutyl phthalate (MiBP) and mono-n-butyl phthalate (MnBP) were above 50 microg/g Cr. The median concentrations of the three secondary metabolites of di-2-ethylhexyl phthalate (DEHP) were greater than 20 microg/g Cr. The data indicate that the Generation R study population provides a wide distribution of selected environmental exposures. Reasons for the relatively high levels and possible health effects need investigation.

Occupational exposure to 60-Hertz magnetic fields and risk of breast cancer in women

&NA; We used data from a large population‐based case‐control study to test the hypothesis that women whose “usual occupation” entailed exposure to higher than background 60‐Hz magnetic fields had a higher risk of breast cancer than women without such exposure. Breast cancer cases were identified from four statewide tumor registries, and controls were randomly selected from lists of licensed drivers and Medicare beneficiaries. Information on usual occupation and breast cancer risk factors was obtained by telephone interview. We calculated adjusted odds ratios from logistic regression models for women holding occupations with potential for low, medium, or high magnetic field exposure, compared with background exposure. There was a modest increase in risk for women with potential for high exposure [odds ratio (OR) = 1.43; 95% confidence interval (CI) = 0.99‐2.09], and no increase for women with potential for medium (OR = 1.09; 95% CI = 0.83‐1.42) or low (OR = 1.02; 95% CI = 0.91‐1.15) exposure. The risk among premenopausal women in the highest‐exposure category was higher (OR = 1.98; 95% CI = 1.04‐3.78) than for postmenopausal women (OR = 1.33; 95% CI = 0.82‐2.17).

Evaluation of the Association between Arsenic and Diabetes: A National Toxicology Program Workshop Review

Background: Diabetes affects an estimated 346 million persons globally, and total deaths from diabetes are projected to increase > 50% in the next decade. Understanding the role of environmental chemicals in the development or progression of diabetes is an emerging issue in environmental health. In 2011, the National Toxicology Program (NTP) organized a workshop to assess the literature for evidence of associations between certain chemicals, including inorganic arsenic, and diabetes and/or obesity to help develop a focused research agenda. This review is derived from discussions at that workshop. Objectives: Our objectives were to assess the consistency, strength/weaknesses, and biological plausibility of findings in the scientific literature regarding arsenic and diabetes and to identify data gaps and areas for future evaluation or research. The extent of the existing literature was insufficient to consider obesity as an outcome. Data Sources, Extraction, and Synthesis: Studies related to arsenic and diabetes or obesity were identified through PubMed and supplemented with relevant studies identified by reviewing the reference lists in the primary literature or review articles. Conclusions: Existing human data provide limited to sufficient support for an association between arsenic and diabetes in populations with relatively high exposure levels (≥ 150 µg arsenic/L in drinking water). The evidence is insufficient to conclude that arsenic is associated with diabetes in lower exposure (< 150 µg arsenic/L drinking water), although recent studies with better measures of outcome and exposure support an association. The animal literature as a whole was inconclusive; however, studies using better measures of diabetes-relevant end points support a link between arsenic and diabetes.

Use of selenium concentration in whole blood, serum, toenails, or urine as a surrogate measure of selenium intake.

&NA; We examined the validity of using the selenium level in a single biological specimen as a surrogate measure of usual intake. We used data from 77 free‐living adults from South Dakota and Wyoming. Subjects provided multiple 1‐day duplicate‐plate food composites, repeated specimens of blood and toenails, and 24‐hour urine collections. We developed a statistical calibration method that incorporated measurement error correction to analyze the data. The Pearson correlation coefficients between selenium intake and a single selenium status measure, after deattenuation to adjust for the effect of within‐person variation in intake, were: 0.78 for whole blood, 0.74 for serum, 0.67 for toenails, and 0.86 for urine. We present formulas to estimate the intake of individuals, based on selenium levels in a single specimen of blood, toenails, or urine. In these data, the concentration of selenium in a single specimen of whole blood, serum, or toenails served reasonably well as a measure for ranking subjects according to long‐term selenium intake but provided only a rough estimate of intake for each subject.

Anogenital distance in human male and female newborns: a descriptive, cross-sectional study

BackgroundIn animal studies of the effects of hormonally active agents, measurement of anogenital distance (AGD) is now routine, and serves as a bioassay of fetal androgen action. Although measurement of AGD in humans has been discussed in the literature, to our knowledge it has been measured formally in only two descriptive studies of females. Because AGD has been an easy-to-measure, sensitive outcome in animals studies, we developed and implemented an anthropometric protocol for measurement of AGD in human males as well as females.MethodsWe first evaluated the reliability of the AGD measures in 20 subjects. Then measurements were taken on an additional 87 newborns (42 females, 45 males). All subjects were from Morelos, Mexico.ResultsThe reliability (Pearson r) of the AGD measure was, for females 0.50, and for males, 0.64. The between-subject variation in AGD, however, was much greater than the variation due to measurement error. The AGD measure was about two-fold greater in males (mean, 22 mm) than in females (mean, 11 mm), and there was little overlap in the distributions for males and females.ConclusionThe sexual dimorphism of AGD in humans comprises prima facie evidence that this outcome may respond to in utero exposure to hormonally active agents.

Serum dioxin level in relation to diabetes mellitus among Air Force veterans with background levels of exposure

Data from several epidemiologic studies suggest that exposure to unusually high amounts of dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) increases the risk of diabetes mellitus, and experimental data suggest that the mechanism for this is decreased cellular glucose uptake. To investigate the dose-response relation more closely, we examined the association of serum dioxin level with prevalence of diabetes mellitus and with levels of serum insulin and glucose among 1,197 veterans in the Air Force Health Study who never had contact with dioxin-contaminated herbicides and whose serum dioxin level was within the range of background exposure typically seen in the United States (< or =10 ng/kg lipid). Compared with those whose serum dioxin level was in the first quartile (<2.8 ng/kg lipid), the multivariate-adjusted odds of diabetes among those in the highest quartile (> or =5.2 ng/kg lipid) was 1.71 (95% confidence interval = 1.00-2.91). The association was slightly attenuated after adjustment for serum triglycerides. Whether adjustment for serum triglycerides was appropriate, however, cannot be determined with available data. The association of background-level dioxin exposure with the prevalence of diabetes in these data may well be due to reasons other than causality, although a causal contribution cannot be wholly dismissed.

Alcohol consumption and risk of cancer in humans: An overview☆

Recent epidemiologic data continue to support alcoholic beverage consumption as a cause of cancer of the mouth, pharynx, larynx, esophagus, and liver. The effect of a given alcohol intake on absolute risk of these cancers depends on the prevalence of other risk factors. Whether alcoholic beverage consumption is a cause of cancer of the breast or large bowel is unclear. Alcohol intake appears not to increase risk of cancer of the lung, bladder, prostate, stomach, ovary, endometrium, or of melanoma. Indirect epidemiologic evidence suggests that alcohol may be a weak causal factor for pancreatic cancer. Additional research is needed to determine whether middle-aged women who drink moderately may experience a slight increase in longevity if they decrease alcohol intake. A number of biologically plausible mechanisms exist by which alcohol may cause cancer.