On recent meta-analyses of exposure to glyphosate and risk of non-Hodgkin's lymphoma in humans.

PURPOSE: A recent meta-analysis of five case-control studies and one cohort study reported that exposure to glyphosate was associated with increased risk of non-Hodgkin's lymphoma (NHL). The meta-analysis was based on estimates of risk from the included studies at the highest reported exposure level obtained from analyses with the longest lag period. The extent to which the summary estimate depends upon the exposure definitions and assumed latency period is uncertain. METHODS: We carried out sensitivity analyses to determine how the definition of exposure and the choice of latency period affect the summary estimate from meta-analyses of the 6 studies included in the recent meta-analysis. We also conducted a meta-analysis of ever-exposure to glyphosate incorporating the most updated results from the case-control studies. RESULTS: The summary estimates of risk varied considerably depending on both the assumptions about exposure level and latency. Using the highest reported exposure levels, evidence of an association between glyphosate and NHL was strongest when estimates from analyses in the cohort study with a 20-year lag [RR = 1.41 (95% CI 1.13-1.76)] and a 15-year lag [RR = 1.25 (95% CI 1.01-1.25)] were included. In our meta-analysis of ever-exposure with no lag period, the summary relative risk with updated estimates was 1.05 (95% CI 0.87-1.28). CONCLUSION: The results of meta-analyses of glyphosate exposure and NHL risk depend on assumptions made about both exposure level and latency period. Our results for ever-exposure are consistent with those of two recent meta-analyses conducted using somewhat different study inclusion criteria.

On the International Agency for Research on Cancer classification of glyphosate as a probable human carcinogen.

The recent classification by International Agency for Research on Cancer (IARC) of the herbicide glyphosate as a probable human carcinogen has generated considerable discussion. The classification is at variance with evaluations of the carcinogenic potential of glyphosate by several national and international regulatory bodies. The basis for the IARC classification is examined under the assumptions that the IARC criteria are reasonable and that the body of scientific studies determined by IARC staff to be relevant to the evaluation of glyphosate by the Monograph Working Group is sufficiently complete. It is shown that the classification of glyphosate as a probable human carcinogen was the result of a flawed and incomplete summary of the experimental evidence evaluated by the Working Group. Rational and effective cancer prevention activities depend on scientifically sound and unbiased assessments of the carcinogenic potential of suspected agents. Implications of the erroneous classification of glyphosate with respect to the IARC Monograph Working Group deliberative process are discussed.

Menthol and Nonmenthol Cigarette Smoking: All-Cause Deaths, Cardiovascular Disease Deaths, and Other Causes of Death Among Blacks and Whites.

BACKGROUND: In contrast to whites, black smokers prefer menthol cigarettes over nonmenthol cigarettes by a large margin and tend to have higher mortality from several smoking-related diseases than whites, raising the possibility that menthol cigarettes contribute to racial disparities in risk. Evidence for differential associations between menthol and nonmenthol cigarettes indicates lower cancer risk for menthol smokers, but for cardiovascular disease (CVD) mortality, evidence has been inconsistent. METHODS AND RESULTS: Cox proportional hazards models were used to compute hazard ratios and accompanying 95% confidence intervals for all-cause and CVD mortality for menthol compared with nonmenthol cigarette smokers among 65 600 participants in the Southern Community Cohort Study, an ongoing community-based cohort with the largest number of menthol smokers being traced. Among the 27 619 current cigarette smokers, 4224 died during follow-up, with 1130 deaths attributed to CVD. Both all-cause (hazard ratio=0.93; 95% confidence interval=0.86-1.01; P=0.10) and CVD (hazard ratio=0.88; 95% confidence interval=0.76-1.03; P=0.10) mortality risks were similar in menthol compared with nonmenthol cigarette smokers. CONCLUSIONS: Smoking regardless of cigarette type is hazardous to health, but these results do not indicate that menthol cigarettes are associated with greater CVD risks than nonmenthol cigarettes.

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.

Five-year reliability of key demographic and life history data collected from self-respondents and next-of-kin.

The ability of study participants or their next-of-kin to provide basic demographic and life history data is of critical importance in epidemiologic studies and government surveys. Most interview studies to date have focused on the reliability of these variables either as self-reported over short periods of time (<2 years) or as reported by the next-of-kin concurrently with the study participant. In a unique reinterview study, the authors examine the concordance of responses 5 years after the initial interview among 196 surviving study participants and 107 next-of-kin respondents of participants who died after the first interview. The reliability of demographic, anthropometric, reproductive, and residential history questions was high overall, with most κ and Spearman rank-correlation coefficients being above 0.80 for both self-respondents and next-of-kin at reinterview in 1985. In particular, almost perfect agreement was observed for year of birth, religion raised, number of children, and age at first birth, whereas agreement was lowest for childhood residential history. Contrary to expectation, the next-of-kin responses were generally as reliable as those of the original participants themselves 5 years after the initial study, providing further support for the usefulness of surrogate respondents in collecting demographic and life history information in epidemiologic investigations when no other source is available.

A prospective study of statin use and mortality among 67,385 blacks and whites in the Southeastern United States.

PURPOSE: The primary objective of this study is to examine the race-specific associations between statin use and overall mortality, as well as cardiovascular and cancer mortality, among blacks and whites in the Southeastern United States (US). Little is known about these associations in blacks. PATIENTS AND METHODS: The Southern Community Cohort Study is an ongoing, prospective cohort study, which enrolled from 2002 through 2009 nearly 86,000 participants aged 40-79 years. We used Cox regression models to estimate race-specific hazard ratios (HRs) and 95% confidence intervals (CI) for overall and cause-specific mortality associated with statin use based on self-reported hypercholesterolemia and treatment at cohort entry. Mean age at cohort entry was 51.4 years in blacks (n=48,825) and 53.5 years in whites (n=18,560). Sixty-one percent of participants were women. Whites were more likely to have self-reported hypercholesterolemia (40% versus 27%, P<0.001), and to report being treated with either statins (52% versus 47%, P<0.001) or combination lipid therapy (9% versus 4%, P<0.001) compared with blacks, regardless of sex. During follow-up (median: 5.6 years) 5,199 participants died. Compared with untreated hypercholesterolemic individuals, statin use was associated with reduced all-cause mortality (adjusted HR [aHR] 0.86; 95% CI 0.77-0.95) and cardiovascular disease mortality overall (aHR 0.75; 95% CI 0.64-0.89) and among whites (aHR 0.67; 95% CI 0.50-0.90), blacks (aHR, 0.80; 95% CI 0.65-0.98), men (aHR 0.70; 95% CI 0.55-0.90), and women (aHR 0.79; 95% CI 0.63-0.99) (P>0.05 for race and sex interaction). Statin use was not associated with cancer mortality overall or in subgroup analyses. CONCLUSION: Regardless of race or sex, self-reported statin use was linked to reduced all-cause and cardiovascular disease mortality. However, factors contributing to the modestly lower statin use and markedly lower prevalence of self-reported hypercholesterolemia among blacks remain to be determined.

False positives in cancer epidemiology.

BACKGROUND: A recent attempt to estimate the false-positive rate for cancer epidemiology studies is based on agents in International Agency for Research on Cancer (IARC) category 3 (agent not classifiable as to its carcinogenicity to humans) in the IARC Monographs Program. METHODS: The estimation method is critiqued regarding biases caused by its reliance on the IARC classification criteria for assessing carcinogenic potential. RESULTS: The privileged position given to epidemiologic studies by the IARC criteria ensures that the percentage of positive epidemiologic studies for an agent will depend strongly on the IARC category to which the agent is assigned. Because IARC category 3 is composed of agents with the lowest-assessed carcinogenic potential to which the estimation approach in question could be applied, a spuriously low estimated false-positive rate was necessarily the outcome of this approach. CONCLUSIONS: Tendentious estimation approaches like that employed will by necessity produce spuriously low and misleading false positive rates. IMPACT: The recently reported estimates of the false-positive rate in cancer epidemiology are seriously biased and contribute nothing substantive to the literature on the very real problems related to false-positive findings in epidemiology.

Incidence and predictors of end stage renal disease among low-income blacks and whites.

We evaluated whether black race is associated with higher incidence of End Stage Renal Disease (ESRD) among a cohort of blacks and whites of similar, generally low socioeconomic status, and whether risk factor patterns differ among blacks and whites and explain the poorly understood racial disparity in ESRD. Incident diagnoses of ESRD among 79,943 black and white participants in the Southern Community Cohort Study (SCCS) were ascertained by linkage with the United States Renal Data System (USRDS) from 2002 through 2009. Person-years of follow up were calculated from date of entry into the SCCS until date of ESRD diagnosis, date of death, or September 1, 2009, whichever occurred first. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for incident ESRD among black and white participants in relation to baseline characteristics. After 329,003 person-years of follow-up, 687 incident cases of ESRD were identified in the cohort. The age-adjusted ESRD incidence rate was 273 (per 100,000) among blacks, 3.5-fold higher than the rate of 78 among whites. Risk factors for ESRD included male sex (HR = 1.6; 95% CI 1.4-1.9), low income (HR = 1.5; 95% CI 1.2-1.8 for income below vs. above $15,000), smoking (HR = 1.2; 95% CI 1.02-1.4) and histories of diabetes (HRs increasing to 9.4 (95% CI 7.4-11.9) among those with ≥20 years diabetes duration) and hypertension (HR = 2.9; 95% CI 2.3-3.7). Patterns and magnitudes of association were virtually identical among blacks and whites. After adjustment for these risk factors, blacks continued to have a higher risk for ESRD (HR = 2.4; 95% CI = 1.9-3.0) relative to whites. The black-white disparity in risk of ESRD was attenuated but not eliminated after control for known risk factors in a closely socioeconomically matched cohort. Further research characterizing biomedical factors, including CKD progression, in ESRD occurrence in these two racial groups is needed.

Cancer incidence among workers at a satellite manufacturing facility.

OBJECTIVE: To evaluate cancer incidence overall and renal cancer in particular among workers at the Valley Forge satellite manufacturing complex in Pennsylvania. A previous mortality study observed a slightly elevated risk estimate for brain cancer. METHODS: A cohort of 27,586 workers, employed between 1962 and 2008 and alive in 1990 when cancer follow-up began, was investigated. Standardized incidence ratios (SIRs) were calculated. RESULTS: A total of 4303 incident cancers were diagnosed. The SIRs were significantly reduced for all cancers (0.88; 95% confidence interval [CI], 0.85 to 0.90) and several site-specific cancers. The renal cancer SIR was 1.00 (95% CI, 0.84 to 1.19) and the brain cancer SIR was 1.17 (95% CI, 0.90 to 1.49). CONCLUSIONS: This cancer incidence study of satellite manufacturing workers found no convincing evidence of increased cancer risk overall, or for renal or brain cancer in particular.

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.

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.

Renal cancer paradox: higher incidence but not higher mortality among African-Americans.

To compare temporal trends in the incidence and mortality of renal cell cancer among blacks and whites for clues to etiologic differences. We examined trends in age-adjusted and age-specific Surveillance Epidemiology and End Results incidence and US mortality rates for renal cancer for 1973 through 2007, as well as nephrectomy rates from surgery codes for kidney cancer for 2000 through 2007. For nearly four decades, incidence rates for renal cell cancer have been rising more rapidly among blacks than whites, leading to a shift in excess from among whites to among blacks, almost entirely accounted for by an excess of localized disease. The incidence patterns are puzzling, as localized renal cell cancer is primarily detected incidentally by imaging, to which blacks have historically had less access. In contrast to the incidence patterns, there has been an unexpected convergence of renal cancer mortality rates, which have been virtually identical among blacks and whites since the early 1990 s. Nephrectomy rates, regardless of stage, were lower among blacks than among whites, despite almost identical cause-specific survival rates in both races. The identical mortality patterns, combined with higher and more rapidly increasing incidence and lower rates of nephrectomies among blacks, suggest that renal cell cancer may tend to be a less aggressive tumor in blacks. This hypothesis is supported by the favorable stage distribution among blacks and their higher survival for distant and unstaged cancer. Further research into the enigmatic descriptive epidemiology and the biology and natural history of renal cell cancer may shed light on the etiology of this malignancy and its more frequent occurrence among black Americans.