Jennifer S. Sonderman

Review of epidemiologic studies of dietary acrylamide intake and the risk of cancer.

Conjectured associations between dietary acrylamide intake and cancer have been evaluated in more than 15 epidemiologic studies examining almost every major cancer site. We have critically reviewed the epidemiologic studies of estimated dietary acrylamide exposure and cancer. As substantially greater acrylamide exposure occurs through tobacco smoke than dietary exposure, we present the results separately for never smokers or adjusted statistically for smoking status, where possible. After an extensive examination of the published literature, we found no consistent or credible evidence that dietary acrylamide increases the risk of any type of cancer in humans, either overall or among nonsmokers. In particular, the collective evidence suggests that a high level of dietary acrylamide intake is not a risk factor for breast, endometrial, or ovarian cancers, which have generated particular interest because of a conjectured hormonal mechanism of acrylamide. Moreover, the absence of a positive association between smoking and ovarian and endometrial cancers suggests that any association of these cancers with the much lower, more sporadic dietary acrylamide intake is unlikely. In conclusion, epidemiologic studies of dietary acrylamide intake have failed to demonstrate an increased risk of cancer. In fact, the sporadically and slightly increased and decreased risk ratios reported in more than two dozen papers examined in this review strongly suggest the pattern one would expect to find for a true null association over the course of a series of trials. Therefore, continued epidemiologic investigation of acrylamide and cancer risk appears to be a misguided research priority.

Individual and neighborhood-level socioeconomic characteristics in relation to smoking prevalence among black and white adults in the Southeastern United States: a cross-sectional study

BackgroundLow individual-level socioeconomic status (SES) is associated with higher prevalence of cigarette smoking. Recent work has examined whether neighborhood-level SES may affect smoking behavior independently from individual-level measures. However, few comparisons of neighborhood-level effects on smoking by race and gender are available.MethodsCross-sectional data from adults age 40-79 enrolled in the Southern Community Cohort Study from 2002-2009 (19, 561 black males; 27, 412 black females; 6, 231 white males; 11, 756 white females) were used in Robust Poisson regression models to estimate prevalence ratios (PRs) and 95% confidence intervals (CI) for current smoking in relation to individual-level SES characteristics obtained via interview and neighborhood-level SES characteristics represented by demographic measures from US Census block groups matched to participant home addresses.ResultsSeveral neighborhood-level SES characteristics were modestly associated with increased smoking after adjustment for individual-level factors including lower percentage of adults with a college education and lower percentage of owner-occupied households among blacks but not whites; lower percentage of households with interest, dividends, or net rental income among white males; and lower percentage of employed adults among black females.ConclusionsLower neighborhood-level SES is associated with increased smoking suggesting that cessation programs may benefit from targeting higher-risk neighborhoods as well as individuals.

Cancer mortality among aircraft manufacturing workers: An extended follow-up

Objective: Extended cancer follow-up among 77,943 aircraft workers. Methods: Comprehensive exposure information enabled detailed classification of trichloroethylene (TCE), perchloroethylene (PCE), mixed solvents, and chromates exposure among these workers. Results: Exposure to TCE, PCE, mixed solvents or chromates was not associated with increased cancer risk overall or for most cancer sites. Elevated rates compared with the general population were seen for non-Hodgkin lymphoma for PCE exposure, and colon and testicular cancers and multiple myeloma for mixed solvents exposure. Internal cohort analyses, however, showed no significant trends of increasing risk for these cancers with increasing years of exposure to TCE, PCE or mixed solvents. Conclusion: This large, long-term cohort study with comprehensive exposure assessment found no consistent evidence of increased cancer risk overall or by site among aircraft workers, including those with long-term exposure to TCE, PCE, and mixed solvents.

A pooled analysis of body mass index and pancreatic cancer mortality in African Americans

Background: Pancreatic cancer is a leading cause of cancer-related mortality in the United States and both incidence and mortality are highest in African Americans. Obesity is also disproportionately high in African Americans, but limited data are available on the relation of obesity to pancreatic cancer in this population. Methods: Seven large prospective cohort studies pooled data from African American participants. Body mass index (BMI) was calculated from self-reported height and weight at baseline. Cox regression was used to calculate HRs and 95% confidence intervals (CI) for levels of BMI relative to BMI 18.5–24.9, with adjustment for covariates. Primary analyses were restricted to participants with ≥5 years of follow-up because weight loss before diagnosis may have influenced baseline BMI in cases who died during early follow-up. Results: In follow-up of 239,597 participants, 897 pancreatic cancer deaths occurred. HRs were 1.08 (95% CI, 0.90–1.31) for BMI 25.0 to 29.9, 1.25 (95% CI, 0.99–1.57) for BMI 30.0 to 34.9, and 1.31 (95% CI, 0.97–1.77) for BMI ≥35.0 among those with ≥5 years of follow-up (Ptrend = 0.03). The association was evident among both sexes and was independent of a history of diabetes. A stronger association was observed among never-smokers (BMI ≥30 vs. referent: HR = 1.44; 95% CI, 1.02–2.03) than among smokers (HR = 1.16; 95% CI, 0.87–1.54; Pinteraction = 0.02). Conclusion: The findings suggest that obesity is independently associated with increased pancreatic cancer mortality in African Americans. Impact: Interventions to reduce obesity may also reduce risk of pancreatic cancer mortality, particularly among never-smokers. Cancer Epidemiol Biomarkers Prev; 23(10); 2119–25. ©2014 AACR.

Mortality Among Mound Workers Exposed to Polonium-210 and Other Sources of Radiation, 1944–1979

Polonium-210 is a naturally occurring radioactive element that decays by emitting an alpha particle. It is in the air we breathe and also a component of tobacco smoke. Polonium-210 is used as an anti-static device in printing presses and gained widespread notoriety in 2006 after the poisoning and subsequent death of a Russian citizen in London. More is known about the lethal effects of polonium-210 at high doses than about late effects from low doses. Cancer mortality was examined among 7,270 workers at the Mound nuclear facility near Dayton, OH where polonium-210 was used (1944–1972) in combination with beryllium as a source of neutrons for triggering nuclear weapons. Other exposures included external gamma radiation and to a lesser extent plutonium-238, tritium and neutrons. Vital status and cause of death was determined through 2009. Standardized mortality ratios (SMRs) were computed for comparisons with the general population. Lifetime occupational doses from all places of employment were sought and incorporated into the analysis. Over 200,000 urine samples were analyzed to estimate radiation doses to body organs from polonium and other internally deposited radionuclides. Cox proportional hazards models were used to evaluate dose-response relationships for specific organs and tissues. Vital status was determined for 98.7% of the workers of which 3,681 had died compared with 4,073.9 expected (SMR 0.90; 95% CI 0.88–0.93). The mean dose from external radiation was 26.1 mSv (maximum 939.1 mSv) and the mean lung dose from external and internal radiation combined was 100.1 mSv (maximum 17.5 Sv). Among the 4,977 radiation workers, all cancers taken together (SMR 0.86; 95% CI 0.79–0.93), lung cancer (SMR 0.85; 95% CI 0.74–0.98), and other types of cancer were not significantly elevated. Cox regression analysis revealed a significant positive dose-response trend for esophageal cancer [relative risk (RR) and 95% confidence interval at 100 mSv of 1.54 (1.15–2.07)] and a negative dose-response trend for liver cancer [RR (95% CI) at 100 mSv of 0.55 (0.23–1.32)]. For lung cancer the RR at 100 mSv was 1.00 (95% CI 0.97–1.04) and for all leukemias other than chronic lymphocytic leukemia (CLL) it was 1.04 (95% CI 0.63–1.71). There was no evidence that heart disease was associated with exposures [RR at 100 mSv of 1.06 (0.95–1.18)]. Assuming a relative biological effectiveness factor of either 10 or 20 for polonium and plutonium alpha particle emissions had little effect on the dose-response analyses. Polonium was the largest contributor to lung dose, and a relative risk of 1.04 for lung cancer at 100 mSv could be excluded with 95% confidence. A dose related increase in cancer of the esophagus was consistent with a radiation etiology but based on small numbers. A dose-related decrease in liver cancer suggests the presence of other modifying factors of risk and adds caution to interpretations. The absence of a detectable increase in total cancer deaths and lung cancer in particular associated with occupational exposures to polonium (mean lung dose 159.8 mSv), and to plutonium to a lesser extent (mean lung dose 13.7 mSv), is noteworthy but based on small numbers. Larger combined studies of U.S. workers are needed to clarify radiation risks following prolonged exposures and radionuclide intakes.

Adherence to Cancer Prevention Guidelines and Cancer Risk in Low-Income and African American Populations

Background: The American Cancer Society (ACS) publishes behavioral guidelines for cancer prevention, including standards on body weight, physical activity, nutrition, alcohol, and tobacco use. The impact of these guidelines has been rarely studied in low-income and African American populations. Methods: The study included 61,098 racially diverse, mainly low-income adults who participated in the Southern Community Cohort Study and were followed for a median of 6 years. Cox models were used to estimate HRs for cancer incidence associated with behaviors and with an ACS physical activity/nutrition 0-to-4 compliance score indicating the number of body weight, physical activity, healthy eating, and alcohol guidelines met. Results: During the study period, 2,240 incident cancers were identified. Significantly lower cancer incidence was found among never smokers and non/moderate alcohol drinkers, but not among those meeting guidelines for obesity, physical activity, and diet. The ACS compliance score was inversely associated with cancer risk among the 25,509 participants without baseline chronic disease. HRs for cancer incidence among those without baseline chronic diseases and who met one, two, three, or four guidelines versus zero guidelines were 0.93 (95% confidence intervals, 0.71–1.21), 0.85 (0.65–1.12), 0.70 (0.51–0.97), and 0.55 (0.31–0.99), respectively. Associations were consistent in analyses stratified by sex, race, household income, and smoking status. Conclusions: Meeting the ACS smoking and body weight/physical activity/dietary/alcohol guidelines for cancer prevention is associated with reductions in cancer incidence in low-income and African American populations. Impact: This study provides strong evidence supporting lifestyle modification to lower cancer incidence in these underserved populations. Cancer Epidemiol Biomarkers Prev; 25(5); 846–53. ©2016 AACR.

Acrylamide: a human cancer risk?

Exposure to normoxic conditions is necessary (Kung et al., 2000; Zhang et al., 2004; Gillespie et al., 2007) as the oxygen levels of subcutaneously xenografted (BALB/c nude mice) measured by Lawrentschuk et al. (2011) were not equal to hypoxia (2% O2) in an in-vitro condition (Zhou et al., 2012). In addition, the decrease in the HIF-1a protein under both a normoxic and a hypoxic condition may indicate the inhibition of proteasomal degradation (Gillespie et al., 2007). The efficiency of a recombinant retroviral vector can also be established at the protein level.

Intraindividual Variation in One-Carbon Metabolism Plasma Biomarkers

Interest in the relationship between one-carbon metabolism (OCM) and carcinogenesis is intensifying, leading to increased use of related biomarkers as measures of exposure. Little is known, however, about the intraindividual variation in these markers and whether or not the use of a single measure is appropriate for assessing exposure–disease relationships in epidemiologic studies. We evaluated the intraindividual variation in plasma concentrations of 19 OCM biomarkers in a sample of 147 African American and 68 non-Hispanic white participants from the Southern Community Cohort Study who donated blood samples and responded to questionnaires at two time points from 2005 to 2008. Weighted kappa coefficients (κ) were calculated to assess the agreement between quartile assignments based on the repeated measures. Adjusted intraclass correlation coefficients (ICC) were also used to assess the consistency of the two measurements. Most (16/19) OCM biomarkers showed a moderate or better agreement for quartile assignment at the two time points, with only methionine, methionine sulfoxide, and cystathionine having κ ≤ 0.40. The median-adjusted ICC across the 19 biomarkers was 0.60. Reproducibility was highest for flavin mononucleotide [ICC = 0.84, 95% confidence interval (CI), 0.79–0.87] and lowest for methionine and its oxidative product methionine sulfoxide (ICC = 0.22, 95% CI 0.09–0.34; ICC = 0.20, 95% CI 0.07–0.32, respectively). Overall, the intraindividual variation in OCM biomarkers was similar for African Americans and whites and for males and females. Our results suggest that with the exception of methionine and methionine sulfoxide, OCM biomarkers generally have good intraindividual reproducibility and can be considered as reliable exposure measures in epidemiologic studies. Cancer Epidemiol Biomarkers Prev; 22(10); 1894–9. ©2013 AACR.

Discordance between Self-Report and Genetic Confirmation of Sickle Cell Disease Status in African-American Adults

Background: Sickle cell disease (SCD) is an autosomal recessive genetic disorder, with persons heterozygous for the mutation said to have the sickle cell trait (SCT). Serious adverse effects are mainly limited to those with SCD, but the distinction between disease and trait is not always clear to the general population. We sought to determine the accuracy of self-reported SCD when compared to genetic confirmation. Methods: From stratified random samples of Southern Community Cohort Study participants, we sequenced the β- globin gene in 51 individuals reporting SCD and 75 individuals reporting no SCD. Results: The median age of the group selected was 53 years (range 40-69) with 29% male. Only 5.9% of the 51 individuals reporting SCD were confirmed by sequencing, with the remaining 62.7% having SCT, 5.9% having hemoglobin C trait, and 25.5% having neither SCD nor trait. Sequencing results of the 75 individuals reporting no SCD by contrast were 100% concordant with self-report. Conclusions: Misreporting of SCD is common in an older adult population, with most persons reporting SCD in this study being carriers of the trait and a sizeable minority completely unaffected. The results from this pilot survey support the need for increased efforts to raise community awareness and knowledge of SCD.

Suicides, homicides, accidents, and other external causes of death among blacks and whites in the Southern Community Cohort Study.

Prior studies of risk factors associated with external causes of death have been limited in the number of covariates investigated and external causes examined. Herein, associations between numerous demographic, lifestyle, and health-related factors and the major causes of external mortality, such as suicide, homicide, and accident, were assessed prospectively among 73,422 black and white participants in the Southern Community Cohort Study (SCCS). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated in multivariate regression analyses using the Cox proportional hazards model. Men compared with women (HR = 2.32; 95% CI: 1.87–2.89), current smokers (HR = 1.74; 95% CI: 1.40–2.17), and unemployed/never employed participants at the time of enrollment (HR = 1.67; 95% CI 1.38–2.02) had increased risk of dying from all external causes, with similarly elevated HRs for suicide, homicide, and accidental death among both blacks and whites. Blacks compared with whites had lower risk of accidental death (HR = 0.46; 95% CI: 0.38–0.57) and suicide (HR = 0.55; 95% CI: 0.31–0.99). Blacks and whites in the SCCS had comparable risks of homicide death (HR = 1.05; 95% CI: 0.63–1.76); however, whites in the SCCS had unusually high homicide rates compared with all whites who were resident in the 12 SCCS states, while black SCCS participants had homicide rates similar to those of all blacks residing in the SCCS states. Depression was the strongest risk factor for suicide, while being married was protective against death from homicide in both races. Being overweight/obese at enrollment was associated with reduced risks in all external causes of death, and the number of comorbid conditions was a risk factor for iatrogenic deaths. Most risk factors identified in earlier studies of external causes of death were confirmed in the SCCS cohort, in spite of the low SES of SCCS participants. Results from other epidemiologic cohorts are needed to confirm the novel findings identified in this study.