Predicting bone turnover following tobacco exposure using bone alkaline phosphatase and N-telopeptide biomarkers and possible variability and effect modification of these markers by race/ethnicity

Abstract

Introduction: This study investigated the systemic response of serum bone alkaline phosphatase (SBAP) and urinary N-telopeptide (UNTX) to tobacco exposure and environmental tobacco smoke (ETS) and the possible effect modification (and variability) of this response by racial/ethnic origin.

Methods: Data (n?=?5411) were obtained from the National Health and Nutrition Examination Survey, with data analysis done on adults aged ≥ 20?years. Outcome variables were SBAP and UNTX. Independent variable was tobacco exposure measured using serum cotinine levels and adjusted for covariates. Generalized linear models were used to explore associations.

Results: A percentage increase in log transformed serum cotinine was associated with a 0.005 percentage increase in log transformed SBAP (CI: 0.002, 0.008) and 0.02 percentage increase in log transformed UNTX (CI: ?0.01, 0.04) with interaction between cotinine and race/ethnicity (p?=?0.01). Stratifying by race/ethnicity, tobacco exposure was associated with significant decreases in UNTX among non-Hispanic Whites – 0.008(?0.014, ?0.002) and Mexican Americans ?0.014 (?0.025, ?0.002) only. Categories of serum cotinine were associated with a monotonic increase in SBAP (p for trend <0.001) and monotonic non-linear decrease in UNTX (p for trend?>?0.05).

Conclusions: Tobacco and environmental tobacco exposure are associated with SBAP and increased bone formation. The response of UNTX to these exposures is modified by race/ethnicity with non-Hispanic Whites and Mexican-Americans less sensitive to the resorptive effects of tobacco exposure on bone.     

Trends of Abdominal Adiposity in White,Black, and Mexican‐American Adults, 1988 to 2000

Objective: To describe changes in the distribution of waist circumference (WC) and abdominal obesity (AO) in white, black, and Mexican‐American adults from 1988 through 2000. Research Methods and Procedures: Nationally representative cross‐sectional surveys of adults 20 to 79 years of age were examined using data from U.S. National Health and Nutrition Examination Surveys of 1988 to 1994 and 1999 to 2000. AO was defined as WC ≥102 cm in men and ≥88 cm in women. Results: There was a gradient of increasing WC and AO with increasing age in both study periods in whites and blacks. In men, the average increase between the study periods in overall WC in whites, blacks, and Mexican Americans were 3, 3.3, and 3.4 cm, respectively. The corresponding values in women were 2.4, 5.3, and 3.7 cm, respectively. In men, the percentage change in prevalence of AO between 1988 and 2000 ranged from 5.5% in Mexican‐American men to 8.2% in white men. In women, there was a 1.7% decrease in AO in Mexican Americans, whereas there was an increase of 6.3% for whites and 7% for blacks. Discussion: Despite increased understanding of the need for screening and treatment for obesity, this study indicates increasing prevalence of AO in white and black Americans. Without concerted effort to reduce the prevalence of overall obesity, the increasing prevalence of AO is likely to lead to increased prevalence of metabolic syndromes in the United States. Our results highlight the need to design evidence‐based programs that show promise for long‐term health behavior changes to facilitate the prevention of AO and related comorbidities.     

Trends and Disparities in Provider Diagnosis of Overweight Analysis of NHANES 1999–2004

Rates of overweight and obesity are disproportionately high within minority populations. This study examined the trends in provider diagnosis of overweight from 1999 to 2004 and examined whether there were differences in provider diagnosis based on race/ethnicity. We examined data from 4,071 adults with BMI ≥30 who participated in the National Health and Nutrition Examination Surveys (NHANES) (1999–2004). Provider diagnosis was determined by self‐report. From 1999 to 2004, the provider diagnosis of overweight decreased from 71 to 64% (P = 0.003). After controlling for potential confounders, non‐Hispanic blacks and Mexican Americans were less likely to report a provider diagnosis of overweight compared to non‐Hispanic whites. Odds ratio (OR) (95% confidence interval (CI)) for non‐Hispanic blacks was 0.6 (95% CI, 0.4–0.8) and for Mexican Americans was 0.7 (95% CI, 0.4–1.0) compared to non‐Hispanic whites. Reasons for this disparity warrant further investigation.     

Racial/Ethnic Differences in Early-Life Mortality in the United States

U.S. early-life (ages 1–24) deaths are tragic, far too common, and largely preventable. Yet demographers have focused scant attention on U.S. early-life mortality patterns, particularly as they vary across racial and ethnic groups. We employed the restricted-use 1999–2011 National Health Interview Survey–Linked Mortality Files and hazard models to examine racial/ethnic differences in early-life mortality. Our results reveal that these disparities are large, strongly related to differences in parental socioeconomic status, and expressed through different causes of death. Compared to non-Hispanic whites, non-Hispanic blacks experience 60 percent and Mexican Americans 32 percent higher risk of death over the follow-up period, with demographic controls. Our finding that Mexican Americans experience higher early-life mortality risk than non-Hispanic whites differs from much of the literature on adult mortality. We also show that these racial/ethnic differences attenuate with controls for family structure and especially with measures of socioeconomic status. For example, higher mortality risk among Mexican Americans than among non-Hispanic whites is no longer significant once we controlled for mother’s education or family income. Our results strongly suggest that eliminating socioeconomic gaps across groups is the key to enhanced survival for children and adolescents in racial/ethnic minority groups.     

Changes in the salivary cotinine cut-offs to discriminate smokers and non-smokers before and after Spanish smoke-free legislation

IntroductionHigh levels of cotinine in non-smokers indicate passive exposure to tobacco smoke. This study aims to evaluate variations in salivary cotinine cut-offs to discriminate smokers and non-smokers before and after the implementation of smoke-free legislation (Law 28/2005 and Law 42/2010) in a sample of the adult population of Barcelona, Spain.MethodsThis longitudinal study analyzes salivary cotinine samples and self-reported information from a representative sample (n = 676) of the adult population from Barcelona before and after the approval of smoke-free legislation. We calculated the receiver operating characteristic (ROC) curves, to obtain optimal cotinine cut-off points to discriminate between smokers and non-smokers overall, by sex and age, and their corresponding sensitivity, specificity, and area under the curve. We used linear mixed-effects models, with individuals as random effects, to model the percentage change of cotinine concentration before and after the implementation of both laws.ResultsThe mean salivary cotinine concentration was significantly lower post-2010 law (−85.8%, p < 0.001). The ROC curves determined that the optimal cotinine cut-off points for discriminating non-smokers and smokers were 10.8 ng/mL (pre-2005 law) and 5.6 ng/mL (post-2010 law), with a post-2010 law sensitivity of 92.6%, specificity of 98.4%, and an area under the curve of 97.0%. The post-2010 law cotinine cut-off points were 5.6 ng/mL for males and 1.9 ng/mL for females.ConclusionThe implementation of Spanish smoke-free legislation was effective in reducing secondhand smoke exposure and, therefore, also in reducing the cut-off point for salivary cotinine concentration. This value should be used to better assess tobacco smoke exposure in this population.     

Detection of Pleiotropy through a Phenome-Wide Association Study (PheWAS) of Epidemiologic Data as Part of the Environmental Architecture for Genes Linked to Environment (EAGLE) Study

We performed a Phenome-wide association study (PheWAS) utilizing diverse genotypic and phenotypic data existing across multiple populations in the National Health and Nutrition Examination Surveys (NHANES), conducted by the Centers for Disease Control and Prevention (CDC), and accessed by the Epidemiological Architecture for Genes Linked to Environment (EAGLE) study. We calculated comprehensive tests of association in Genetic NHANES using 80 SNPs and 1,008 phenotypes (grouped into 184 phenotype classes), stratified by race-ethnicity. Genetic NHANES includes three surveys (NHANES III, 1999–2000, and 2001–2002) and three race-ethnicities: non-Hispanic whites (n = 6,634), non-Hispanic blacks (n = 3,458), and Mexican Americans (n = 3,950). We identified 69 PheWAS associations replicating across surveys for the same SNP, phenotype-class, direction of effect, and race-ethnicity at p<0.01, allele frequency >0.01, and sample size >200. Of these 69 PheWAS associations, 39 replicated previously reported SNP-phenotype associations, 9 were related to previously reported associations, and 21 were novel associations. Fourteen results had the same direction of effect across more than one race-ethnicity: one result was novel, 11 replicated previously reported associations, and two were related to previously reported results. Thirteen SNPs showed evidence of pleiotropy. We further explored results with gene-based biological networks, contrasting the direction of effect for pleiotropic associations across phenotypes. One PheWAS result was ABCG2 missense SNP rs2231142, associated with uric acid levels in both non-Hispanic whites and Mexican Americans, protoporphyrin levels in non-Hispanic whites and Mexican Americans, and blood pressure levels in Mexican Americans. Another example was SNP rs1800588 near LIPC, significantly associated with the novel phenotypes of folate levels (Mexican Americans), vitamin E levels (non-Hispanic whites) and triglyceride levels (non-Hispanic whites), and replication for cholesterol levels. The results of this PheWAS show the utility of this approach for exposing more of the complex genetic architecture underlying multiple traits, through generating novel hypotheses for future research.     

Tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in smokers in the united states: NHANES 2007–2008

The tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a metabolite of the tobacco-specific nitrosamine (TSNA) 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), has been measured in urine samples from all participants aged 6 years and older from the National Health and Nutrition Examination Survey 2007–2008. Participants with a serum cotinine concentration of ≥10?ng/mL were identified as tobacco users, primarily cigarette smokers. Regression models were developed to calculate geometric mean NNAL concentrations adjusted for serum cotinine, urinary creatinine, cigarettes per day, and Federal Trade Commission tar values of the cigarettes smoked. Significant differences were found by gender (p?=?0.003) and race/ethnicity (p?=?0.022 for non-Hispanic white versus non-Hispanic black smokers), but not by menthol type of the cigarettes. Females and non-Hispanic white smokers had the highest adjusted means for urinary NNAL (353 and 336 pg/mL, respectively). The results from this study demonstrated significant relationships between NNAL concentrations and serum cotinine (p?<?0.001) and urine creatinine (p?<?0.001). The joint effect of linear and quadratic terms for number of cigarettes smoked per day was also statistically significant (p?=?0.001). In addition to addressing current NNK exposure levels, these results will form a baseline for future estimates of tobacco users’ exposure to this carcinogen.     

Estimation of urinary cotinine cut-off points distinguishing non-smokers,passive and active smokers

Abstract

An objective assessment of exposure to tobacco smoke may be accomplished by means of examining particular biomarkers in body fluids. The most common biomarker of tobacco smoke exposure is urinary, or serum, cotinine. In order to distinguish non-smokers from passive smokers and passive smokers from active smokers, it is necessary to estimate cotinine cut-off points. The objective of this article was to apply statistical distribution of urinary cotinine concentration to estimate cut-off points distinguishing the three above-mentioned groups. The examined group consisted of 327 volunteers (187 women and 140 men) who were ethnically homogenous inhabitants of the same urban agglomeration (Sosnowiec, Poland). The values which enabled differentiation of the examined population into groups and subgroups were as follows: 50 µg l^?1 (differentiation of non-smokers from passive smokers), 170 µg l^?1 (to divide the group of passive smokers into two subgroups: minimally and highly exposed to environmental tobacco smoke), 550 µg l^?1 (differentiation of passive smokers from active smokers), and 2100 µg l^?1 (to divide group of active smokers into two subgroups: minimally and highly exposed to tobacco smoke). The results suggest that statistical distribution of urinary cotinine concentration is useful for estimating urinary cotinine cut-off points and for assessing the smoking status of persons exposed to tobacco smoke.     

Room at the top? Minority mobility and the transition to demographic diversity in the USA

We examine the ramifications of the demographic transition to diversity in the USA through an analysis of changes at the top of the occupational hierarchy, as glimpsed in recent census data. We find evidence that, among the incumbents of better-paid occupations, the percentage of non-Hispanic whites, the historically dominant majority, is sharply declining, while the proportion of immigrant-origin minorities, Asians, both foreign and US born, and US-born Hispanics, is growing. African Americans, or US-born blacks, are not so far sharing much in this growth. However, whites still retain important advantages in terms of occupational placement net of education and in terms of earnings net of occupational placement. We conclude overall that demographic shifts are highly likely to drive further diversification at the top of the US workforce; the question of whether whites can hold on to their advantages in the face of these changes cannot be answered yet.     

Variation in LPA is associated with Lp(a) levels in three populations from the Third National Health and Nutrition Examination Survey

The distribution of lipoprotein(a) [Lp(a)] levels can differ dramatically across diverse racial/ethnic populations. The extent to which genetic variation in LPA can explain these differences is not fully understood. To explore this, 19 LPA tagSNPs were genotyped in 7,159 participants from the Third National Health and Nutrition Examination Survey (NHANES III). NHANES III is a diverse population-based survey with DNA samples linked to hundreds of quantitative traits, including serum Lp(a). Tests of association between LPA variants and transformed Lp(a) levels were performed across the three different NHANES subpopulations (non-Hispanic whites, non-Hispanic blacks, and Mexican Americans). At a significance threshold of p<0.0001, 15 of the 19 SNPs tested were strongly associated with Lp(a) levels in at least one subpopulation, six in at least two subpopulations, and none in all three subpopulations. In non-Hispanic whites, three variants were associated with Lp(a) levels, including previously known rs6919246 (p = 1.18 × 10(-30)). Additionally, 12 and 6 variants had significant associations in non-Hispanic blacks and Mexican Americans, respectively. The additive effects of these associated alleles explained up to 11% of the variance observed for Lp(a) levels in the different racial/ethnic populations. The findings reported here replicate previous candidate gene and genome-wide association studies for Lp(a) levels in European-descent populations and extend these findings to other populations. While we demonstrate that LPA is an important contributor to Lp(a) levels regardless of race/ethnicity, the lack of generalization of associations across all subpopulations suggests that specific LPA variants may be contributing to the observed Lp(a) between-population variance.     

Dynamics of human populations

This study expands on earlier findings of racial/ethnic and education–allostatic load associations by assessing whether racial/ethnic differences in allostatic load persist across all levels of educational attainment. This study used data from four recent waves of the National Health and Nutrition Survey (NHANES). Results from this study suggest that allostatic load differs significantly by race/ethnicity and educational attainment overall, but that the race/ethnicity association is not consistent across education level. Analysis of interactions and education-stratified models suggest that allostatic load levels do not differ by race/ethnicity for individuals with low education; rather, the largest allostatic load differentials for Mexican Americans (p < .01) and non-Hispanic blacks (p < .001) are observed for individuals with a college degree or more. These findings add to the growing evidence that differences in socioeconomic opportunities by race/ethnicity are likely a consequence of differential returns to education, which contribute to higher stress burdens among minorities compared to non-Hispanic whites.     

Molecular basis of the apolipoprotein H (β2-glycoprotein I) protein polymorphism

Apolipoprotein H (apoH, protein; APOH, gene) is considered to be an essential cofactor for the binding of certain antiphospholipid autoantibodies to anionic phospholipids. APOH exhibits a genetically determined structural polymorphism due to the presence of three common alleles (APOH*1, APOH*2 and APOH*3 ) detectable by isoelectric focusing (IEF) and immunoblotting. The APOH*3 allele can be further characterized into two subtypes, APOH*3^W and APOH*3^B, based upon its reactivity with monoclonal antibody 3D11. In this study we have determined the molecular basis of the APOH protein polymorphism and its distribution in three large U.S. population samples comprising 661 non-Hispanic whites, 444 Hispanics and 422 blacks. By direct DNA sequencing of PCR amplified fragments corresponding to the eight APOH exons, we identified two missense mutations that correspond to the APOH*1 and APOH*3^W alleles. A missense mutation (G→A) in exon 3, which alters amino acid Ser to Asn at codon 88 and creates a restriction site for TSP509 I, was present in all APOH*1 allele carriers. A second missense mutation (G→C) at codon 316 in exon 8, which replaces amino acid Trp with Ser and creates a restriction site for BSTBI, was present in all APOH*3^W carriers. The distribution of the Ser 88 Asn and Trp 316 Ser mutations was significantly different between the three racial groups. The frequency of the Asn-88 allele was 0.011, 0.043, and 0.056 in blacks, Hispanics and non-Hispanic whites, respectively. While the Ser-316 allele was observed sporadically in blacks (0.008), it was present at a polymorphic frequency in Hispanics (0.027) and non-Hispanic whites (0.059). The identification of the molecular basis of the APOH protein polymorphism will help to elucidate the structural – functional relationship of apoH in the production of antiphospholipid autoantibodies. Received: 20 November 1996 / Accepted: 13 February 1997     

Ethnic Differences in Physical Activity and Inactivity Patterns and Overweight Status

Objective: To examine the relationship between physical activity and inactivity patterns and overweight in U.S. adolescents using baseline and 1-year change in activity and inactivity data. Research Methods and Procedures: Nationally representative data from 12,759 participants (6997 non-Hispanic whites, 2676 non-Hispanic blacks, 2185 Hispanics, and 901 Asians) in the National Longitudinal Study of Adolescent Health (1995 and 1996). Data on moderate to vigorous and low-intensity physical activity, TV/video viewing, and video game/computer use were obtained from questionnaires. Multivariate models assessed the association of overweight (body mass index ≥ 95th percentile Centers for Disease Control and Prevention/National Center for Health Statistics 2000 curves) with initial (and 1-year change) activity and inactivity levels, controlling for age, ethnicity, socioeconomic status, urban residence, cigarette smoking, and region of residence. Results: Overweight prevalence was positively associated with high level TV/video viewing among white boys (odds ratio [OR] = 1.52; 95% confidence interval [1.08 to 2.14]) and girls (OR = 2.45 [1.51 to 3.97]). The odds of overweight decreased with high levels of moderate to vigorous physical activity among white boys (OR = 0.81 [0.76 to 0.87]), non-Hispanic black boys (OR = 0.86 [0.76 to 0.98]) and girls (OR = 0.88 [0.78 to 0.99]), and Hispanic boys (OR = 0.90 [0.83 to 0.97]) and girls (OR = 0.91 [0.84 to 0.99]). Discussion: Predicted probabilities generated from the logistic regression models, which examined the experimental effects of altering hours of TV/video viewing and bouts of moderate to vigorous physical activity, show lower overweight among adolescents who watched less TV per week combined with frequent moderate to vigorous physical activity than those who watched more TV per week combined with fewer bouts of weekly moderate to vigorous physical activity. Predicted probabilities suggest important sex and ethnic differences in these associations.     

Forward to the past: race,the colour scale and Michael Banton

This study examined differences in religious participation and spirituality among African Americans, Caribbean blacks (black Caribbeans) and non-Hispanic whites. Data are taken from the National Survey of American Life, a nationally representative study of African Americans, black Caribbeans and non-Hispanic whites. Selected measures of organizational, non-organizational and subjective religious participation were examined. African American and Caribbean blacks were largely similar in their reports of religious involvement; both groups generally indicated higher levels of religious participation than non-Hispanic whites. African Americans were more likely than black Caribbeans to be official members of their places of worship, engage in activities (choirs, church clubs) at their place of worship and request prayer from others. Black Caribbeans reported reading religious materials more frequently than African Americans. The discussion notes the importance of examining ethnic differences within the black American population of the United States.     

Characterization of mitochondrial haplogroups in a large population-based sample from the United States

Mitochondrial DNA (mtDNA) haplogroups are valuable for investigations in forensic science, molecular anthropology, and human genetics. In this study, we developed a custom panel of 61 mtDNA markers for high-throughput classification of European, African, and Native American/Asian mitochondrial haplogroup lineages. Using these mtDNA markers, we constructed a mitochondrial haplogroup classification tree and classified 18,832 participants from the National Health and Nutrition Examination Surveys (NHANES). To our knowledge, this is the largest study to date characterizing mitochondrial haplogroups in a population-based sample from the United States, and the first study characterizing mitochondrial haplogroup distributions in self-identified Mexican Americans separately from Hispanic Americans of other descent. We observed clear differences in the distribution of maternal genetic ancestry consistent with proposed admixture models for these subpopulations, underscoring the genetic heterogeneity of the United States Hispanic population. The mitochondrial haplogroup distributions in the other self-identified racial/ethnic groups within NHANES were largely comparable to previous studies. Mitochondrial haplogroup classification was highly concordant with self-identified race/ethnicity (SIRE) in non-Hispanic whites (94.8 %), but was considerably lower in admixed populations including non-Hispanic blacks (88.3 %), Mexican Americans (81.8 %), and other Hispanics (61.6 %), suggesting SIRE does not accurately reflect maternal genetic ancestry, particularly in populations with greater proportions of admixture. Thus, it is important to consider inconsistencies between SIRE and genetic ancestry when performing genetic association studies. The mitochondrial haplogroup data that we have generated, coupled with the epidemiologic variables in NHANES, is a valuable resource for future studies investigating the contribution of mtDNA variation to human health and disease.     

Dopamine Transporter Genotype as a Risk Factor for Obesity in African-American Smokers

Objective: To assess the association between a polymorphism related to dopamine function, dopamine transport (SLC6A3), and obesity in smokers. Research Methods and Procedures: Logistic regression was used to assess the relationship between this genetic polymorphism and obesity (body mass index ≥ 30 kg/m²) from a sample of 510 smokers who smoked at least 10 cigarettes per day and who were participating in a study designed to examine genetic and nongenetic predictors of response to a pharmacological treatment. Results: The likelihood of obesity in African Americans (N = 90) with the 10/10 SLC6A3 genotype was 5.16 times that of African Americans with 9/9 or 9/10 SLC6A3 genotypes (odds ratio = 5.16, confidence interval = 1.60 to 16.65). There was no association of the SLC6A3 genotype with obesity for non-Hispanic whites (N = 420). Discussion: These results suggest that variants of the dopamine transporter gene may be related to obesity in African-American smokers. Possible mechanisms responsible for the association between dopamine transport and obesity in African-American smokers are discussed.     

Products of 5-lipoxygenase and myeloperoxidase activities are increased in young male cigarette smokers

Abstract

The significance of 5-lipoxygenase and myeloperoxidase activities has not been extensively studied among young male smokers. Leukotriene B₄, 20-hydroxy-leukotriene B₄, 20-carboxy-leukotriene B₄ and 3-chlorotyrosine were measured in plasma and urinary samples of young male smokers at 8 hours following cigarette abstinence and an hour after cigarette smoking. Leukotriene B₄ and 3-chlorotyrosine were determined in neutrophils isolated from these individuals. The levels of these markers were compared with those of age-matched controls. In vitro studies were performed to evaluate the production of leukotriene B₄ and 3-chlorotyrosine from human neutrophils following exposure to nicotine and cotinine. Thirty male smokers (mean age, 27.4 years) and 28 male non-smokers (mean age, 28.7 years) were studied. Plasma levels of leukotriene B₄, 20-carboxy-leukotriene B₄ and 3-chlorotyrosine were higher in smokers than in non-smokers; leukotriene B₄ and 20-carboxy-leukotriene B₄ levels increased further an hour after cigarette smoking. Peripheral neutrophils isolated from smokers showed greater expressions of myeloperoxidase and 5-lipoxygenase activities compared with non-smokers, while plasma leukotriene B₄ and 3-chlorotyrosine were correlated significantly with high-sensitivity C-reactive protein and plasma nicotine concentrations. Exposure of human neutrophils to nicotine and cotinine resulted in a higher production of leukotriene B₄ and 3-chlorotyrosine. To conclude, leukotriene B₄ and 3-chlorotyrosine levels are increased in young male cigarette smokers. These results suggest that cigarette smoking aggravates neutrophil-mediated inflammation by modulating the activities of myeloperoxidase and 5-lipoxygenase pathways.     

Differential Impact of Obesity in Related Populations

To search for genetic and environmental determinants of obesity, we compared the prevalences and the impact of obesity in three populations from two cities: Mexican Amcricans (n=820) and non-Hispanic whites (n=1112)from San Antonio, Texas, and Mexicans from Mexico City (n= 1878). In the age range examined, 35–64 years, only Mexican men and women showed a significant increase in the prevalence of obesity with age. On the other hand, genetic ancestry, especially in women, made significant differences in the rates of obesity. Mexican Americans showed relatively high, and non-Hispanic whites low, rates of obesity. To discriminate between genetic and environmental influences mediating the impact of obesity on a set of hemodynamic and metabolic variables, we compared this impact between Mexican Americans and both non-Hispanic whites (same macro-environment, different gene pools), and Mexicans (same gene pool, different environments). We found that obesity always worsens the hemodynamic and metabolic profiles of individuals, but the magnitude of the effects may be variable. We showed that the levels of insulin concentrations for a given level of obesity were similar in Mexicans and Mexican Americans, suggesting that genetic influences predominate in determining insulin levels; the levels of triglycerides and HDL for a given level of obesity were similar in Mexican Americans and non-Hispanic whites, suggesting predominant environmental influences on lipid levels. On the other hand, the levels of glucose and systolic blood pressure for a given level of obesity were usually different between Mexican Americans and either of the other two populations, suggesting that these levels may result from genotype-by-environment interactions.     

Quantification of cotinine in dried blood spots as a biomarker of exposure to tobacco smoke

Objective: We present an ultra-sensitive, minimally-invasive method for quantifying cotinine in dried blood spot (DBS) samples as a biomarker of exposure to tobacco smoke that can be collected using a simple heel or finger prick to obtain blood samples.

Methods: Cotinine levels were measured in matched plasma and reconstituted DBS samples from smokers and nonsmokers to evaluate assay parameters. In addition, we applied this new method to finger-prick DBS samples that were collected from infants, children and young adults ages 1–21 to estimate exposure to tobacco smoke. Partitioning of cotinine across red blood cells and haematocrit effects were investigated.

Results: Cotinine levels measured in matched plasma and reconstituted DBS samples from smokers and nonsmokers were found to be highly correlated (R²=0.94), with 100% sensitivity and 94% specificity to differentiate reported smokers from nonsmokers. With this method, the LOQ is <0.25?ng/mL using a single 3.2?mm punch of a DBS, and haematocrit effects are negligible.

Conclusions: This sensitive, high-throughput and minimally-invasive method for quantifying cotinine in DBS samples provides a simple and cost effective means for estimating exposure to tobacco smoke in population based studies, and has particular advantages in studies involving infants and children.     

Social disparities in survival after diagnosis with colorectal cancer: Contribution of race and insurance status

BackgroundBoth minority race and lack of health insurance are risk factors for lower survival in colorectal cancer (CRC) but the interaction between the two factors has not been explored in detail.MethodsOne to 5-year survival by race/ethnic group and insurance type for patients with CRC diagnosed in 2007-13 and registered in the Surveillance Epidemiology, and EndResultsdatabase were explored. Shared frailty models were computed to further explore the association between CRC specific survival and insurance status after adjustment for demographic and treatment variables.ResultsAge-adjusted 5-year survival estimates were 70.4% for non-Hispanic whites (nHW), 62.7% for non-Hispanic blacks (nHB), 70.2% for Hispanics, 64.7% for Native Americans, and 73.1% for Asian/Pacific Islanders (API). Survival was greater for patients with insurance other than Medicaid for all races, but the differential in survival varied with race, with the greatest difference being seen for nHW at +25.0% and +20.2%, respectively, for Medicaid and uninsured versus other insurance. Similar results were observed for stage- and age-specific analyses, with survival being consistently higher for nHW and API compared to other groups. After confounder adjustment, hazard ratios of 1.53 and 1.50 for CRC-specific survival were observed for Medicaid and uninsured. Racial/ethnic differences remained significant only for nHB compared to nHW.ConclusionsRace/ethnic group and insurance type are partially independent factors affecting survival expectations for patients diagnosed with CRC. NHB had lower than expected survival for all insurance types.