Glyphosate is the most commonly used herbicide worldwide, with both residential and agricultural uses. In 2015, the International Agency for Research on Cancer classified glyphosate as "probably ...carcinogenic to humans," noting strong mechanistic evidence and positive associations for non-Hodgkin lymphoma (NHL) in some epidemiologic studies. A previous evaluation in the Agricultural Health Study (AHS) with follow-up through 2001 found no statistically significant associations with glyphosate use and cancer at any site.
The AHS is a prospective cohort of licensed pesticide applicators from North Carolina and Iowa. Here, we updated the previous evaluation of glyphosate with cancer incidence from registry linkages through 2012 (North Carolina)/2013 (Iowa). Lifetime days and intensity-weighted lifetime days of glyphosate use were based on self-reported information from enrollment (1993-1997) and follow-up questionnaires (1999-2005). We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) using Poisson regression, controlling for potential confounders, including use of other pesticides. All statistical tests were two-sided.
Among 54 251 applicators, 44 932 (82.8%) used glyphosate, including 5779 incident cancer cases (79.3% of all cases). In unlagged analyses, glyphosate was not statistically significantly associated with cancer at any site. However, among applicators in the highest exposure quartile, there was an increased risk of acute myeloid leukemia (AML) compared with never users (RR = 2.44, 95% CI = 0.94 to 6.32, Ptrend = .11), though this association was not statistically significant. Results for AML were similar with a five-year (RRQuartile 4 = 2.32, 95% CI = 0.98 to 5.51, Ptrend = .07) and 20-year exposure lag (RRTertile 3 = 2.04, 95% CI = 1.05 to 3.97, Ptrend = .04).
In this large, prospective cohort study, no association was apparent between glyphosate and any solid tumors or lymphoid malignancies overall, including NHL and its subtypes. There was some evidence of increased risk of AML among the highest exposed group that requires confirmation.
Recent increases in incidence and survival of oropharyngeal cancers in the United States have been attributed to human papillomavirus (HPV) infection, but empirical evidence is lacking.
HPV status ...was determined for all 271 oropharyngeal cancers (1984-2004) collected by the three population-based cancer registries in the Surveillance, Epidemiology, and End Results (SEER) Residual Tissue Repositories Program by using polymerase chain reaction and genotyping (Inno-LiPA), HPV16 viral load, and HPV16 mRNA expression. Trends in HPV prevalence across four calendar periods were estimated by using logistic regression. Observed HPV prevalence was reweighted to all oropharyngeal cancers within the cancer registries to account for nonrandom selection and to calculate incidence trends. Survival of HPV-positive and HPV-negative patients was compared by using Kaplan-Meier and multivariable Cox regression analyses.
HPV prevalence in oropharyngeal cancers significantly increased over calendar time regardless of HPV detection assay (P trend < .05). For example, HPV prevalence by Inno-LiPA increased from 16.3% during 1984 to 1989 to 71.7% during 2000 to 2004. Median survival was significantly longer for HPV-positive than for HPV-negative patients (131 v 20 months; log-rank P < .001; adjusted hazard ratio, 0.31; 95% CI, 0.21 to 0.46). Survival significantly increased across calendar periods for HPV-positive (P = .003) but not for HPV-negative patients (P = .18). Population-level incidence of HPV-positive oropharyngeal cancers increased by 225% (95% CI, 208% to 242%) from 1988 to 2004 (from 0.8 per 100,000 to 2.6 per 100,000), and incidence for HPV-negative cancers declined by 50% (95% CI, 47% to 53%; from 2.0 per 100,000 to 1.0 per 100,000). If recent incidence trends continue, the annual number of HPV-positive oropharyngeal cancers is expected to surpass the annual number of cervical cancers by the year 2020.
Increases in the population-level incidence and survival of oropharyngeal cancers in the United States since 1984 are caused by HPV infection.
The field of population genomics has grown rapidly in response to the recent advent of affordable, large-scale sequencing technologies. As opposed to the situation during the majority of the 20th ...century, in which the development of theoretical and statistical population genetic insights outpaced the generation of data to which they could be applied, genomic data are now being produced at a far greater rate than they can be meaningfully analyzed and interpreted. With this wealth of data has come a tendency to focus on fitting specific (and often rather idiosyncratic) models to data, at the expense of a careful exploration of the range of possible underlying evolutionary processes. For example, the approach of directly investigating models of adaptive evolution in each newly sequenced population or species often neglects the fact that a thorough characterization of ubiquitous nonadaptive processes is a prerequisite for accurate inference. We here describe the perils of these tendencies, present our consensus views on current best practices in population genomic data analysis, and highlight areas of statistical inference and theory that are in need of further attention. Thereby, we argue for the importance of defining a biologically relevant baseline model tuned to the details of each new analysis, of skepticism and scrutiny in interpreting model fitting results, and of carefully defining addressable hypotheses and underlying uncertainties.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background Population-based cancer registry data from the Surveillance, Epidemiology, and End Results (SEER) Program at the National Cancer Institute (NCI) are mainly based on medical records and ...administrative information. Individual-level socioeconomic data are not routinely reported by cancer registries in the United States because they are not available in patient hospital records. The U.S. representative National Longitudinal Mortality Study (NLMS) data provide self-reported, detailed demographic and socioeconomic data from the Social and Economic Supplement to the Census Bureau's Current Population Survey (CPS). In 1999, the NCI initiated the SEER-NLMS study, linking the population-based SEER cancer registry data to NLMS data. The SEER-NLMS data provide a new unique research resource that is valuable for health disparity research on cancer burden. We describe the design, methods, and limitations of this data set. We also present findings on cancer-related health disparities according to individual-level socioeconomic status (SES) and demographic characteristics for all cancers combined and for cancers of the lung, breast, prostate, cervix, and melanoma. Methods Records of cancer patients diagnosed in 1973-2001 when residing 1 of 11 SEER registries were linked with 26 NLMS cohorts. The total number of SEER matched cancer patients that were also members of an NLMS cohort was 26,844. Of these 26,844 matched patients, 11,464 were included in the incidence analyses and 15,357 in the late-stage diagnosis analyses. Matched patients (used in the incidence analyses) and unmatched patients were compared by age group, sex, race, ethnicity, residence area, year of diagnosis, and cancer anatomic site. Cohort-based age-adjusted cancer incidence rates were computed. The impact of socioeconomic status on cancer incidence and stage of diagnosis was evaluated. Results Men and women with less than a high school education had elevated lung cancer rate ratios of 3.01 and 2.02, respectively, relative to their college educated counterparts. Those with family annual incomes less than $12,500 had incidence rates that were more than 1.7 times the lung cancer incidence rate of those with incomes $50,000 or higher. Lower income was also associated with a statistically significantly increased risk of distant-stage breast cancer among women and distant-stage prostate cancer among men. Conclusions Socioeconomic patterns in incidence varied for specific cancers, while such patterns for stage were generally consistent across cancers, with late-stage diagnoses being associated with lower SES. These findings illustrate the potential for analyzing disparities in cancer outcomes according to a variety of individual-level socioeconomic, demographic, and health care characteristics, as well as by area measures available in the linked database.
Adolescents and young adults (AYAs) diagnosed with cancer face numerous physical, psychosocial, and practical challenges. This article describes the health-related quality of life (HRQOL) and ...associated demographic and health-related characteristics of this developmentally diverse population.
Data are from the Adolescent and Young Adult Health Outcomes and Patient Experience (AYA HOPE) study, a population-based cohort of 523 AYA patients with cancer, ages 15 to 39 years at diagnosis from 2007 to 2009. Comparisons are made by age group and with general and healthy populations. Multiple linear regression models evaluated effects of demographic, disease, health care, and symptom variables on multiple domains of HRQOL using the Pediatric Quality of Life Inventory (PedsQL) and the Short-Form Health Survey 12 (SF-12).
Overall, respondents reported significantly worse HRQOL across both physical and mental health scales than did general and healthy populations. The greatest deficits were in limitations to physical and emotional roles, physical and social functioning, and fatigue. Teenaged patients (ages 15 to 17 years) reported worse physical and work/school functioning than patients 18 to 25 years old. Regression models showed that HRQOL was worse for those in treatment, with current/recent symptoms, or lacking health insurance at any time since diagnosis. In addition, sarcoma patients, Hispanic patients, and those with high school or lower education reported worse physical health. Unmarried patients reported worse mental health.
Results suggest that AYAs with cancer have major decrements in several physical and mental HRQOL domains. Vulnerable subgroups included Hispanic patients, those with less education, and those without health insurance. AYAs also experienced higher levels of fatigue that were influenced by current symptoms and treatment. Future research should explore ways to address poor functioning in this understudied group.
A recent article reassessing the Neutral Theory of Molecular Evolution claims that it is no longer as important as is widely believed. The authors argue that “the neutral theory was supported by ...unreliable theoretical and empirical evidence from the beginning, and that in light of modern, genome-scale data, we can firmly reject its universality.” Claiming that “the neutral theory has been overwhelmingly rejected,” they propose instead that natural selection is the major force shaping both between-species divergence and within-species variation. Although this is probably a minority view, it is important to evaluate such claims carefully in the context of current knowledge, as inaccuracies can sometimes morph into an accepted narrative for those not familiar with the underlying science. We here critically examine and ultimately reject Kern and Hahn’s arguments and assessment, and instead propose that it is now abundantly clear that the foundational ideas presented five decades ago by Kimura and Ohta are indeed correct.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
CONTEXT Solid organ transplant recipients have elevated cancer risk due to immunosuppression and oncogenic viral infections. Because most prior research has concerned kidney recipients, large studies ...that include recipients of differing organs can inform cancer etiology. OBJECTIVE To describe the overall pattern of cancer following solid organ transplantion. DESIGN, SETTING, AND PARTICIPANTS Cohort study using linked data on solid organ transplant recipients from the US Scientific Registry of Transplant Recipients (1987-2008) and 13 state and regional cancer registries. MAIN OUTCOME MEASURES Standardized incidence ratios (SIRs) and excess absolute risks (EARs) assessing relative and absolute cancer risk in transplant recipients compared with the general population. RESULTS The registry linkages yielded data on 175 732 solid organ transplants (58.4% for kidney, 21.6% for liver, 10.0% for heart, and 4.0% for lung). The overall cancer risk was elevated with 10 656 cases and an incidence of 1375 per 100 000 person-years (SIR, 2.10 95% CI, 2.06-2.14; EAR, 719.3 95% CI, 693.3-745.6 per 100 000 person-years). Risk was increased for 32 different malignancies, some related to known infections (eg, anal cancer, Kaposi sarcoma) and others unrelated (eg, melanoma, thyroid and lip cancers). The most common malignancies with elevated risk were non-Hodgkin lymphoma (n = 1504; incidence: 194.0 per 100 000 person-years; SIR, 7.54 95% CI, 7.17-7.93; EAR, 168.3 95% CI, 158.6-178.4 per 100 000 person-years) and cancers of the lung (n = 1344; incidence: 173.4 per 100 000 person-years; SIR, 1.97 95% CI, 1.86-2.08; EAR, 85.3 95% CI, 76.2-94.8 per 100 000 person-years), liver (n = 930; incidence: 120.0 per 100 000 person-years; SIR, 11.56 95% CI, 10.83-12.33; EAR, 109.6 95% CI, 102.0-117.6 per 100 000 person-years), and kidney (n = 752; incidence: 97.0 per 100 000 person-years; SIR, 4.65 95% CI, 4.32-4.99; EAR, 76.1 95% CI, 69.3-83.3 per 100 000 person-years). Lung cancer risk was most elevated in lung recipients (SIR, 6.13 95% CI, 5.18-7.21) but also increased among other recipients (kidney: SIR, 1.46 95% CI, 1.34-1.59; liver: SIR, 1.95 95% CI, 1.74-2.19; and heart: SIR, 2.67 95% CI, 2.40-2.95). Liver cancer risk was elevated only among liver recipients (SIR, 43.83 95% CI, 40.90-46.91), who manifested exceptional risk in the first 6 months (SIR, 508.97 95% CI, 474.16-545.66) and a 2-fold excess risk for 10 to 15 years thereafter (SIR, 2.22 95% CI, 1.57-3.04). Among kidney recipients, kidney cancer risk was elevated (SIR, 6.66 95% CI, 6.12-7.23) and bimodal in onset time. Kidney cancer risk also was increased in liver recipients (SIR, 1.80 95% CI, 1.40-2.29) and heart recipients (SIR, 2.90 95% CI, 2.32-3.59). CONCLUSION Compared with the general population, recipients of a kidney, liver, heart, or lung transplant have an increased risk for diverse infection-related and unrelated cancers.
Background
Transplant recipients have an elevated risk of cancer because of immunosuppressive medications used to prevent organ rejection, but to the authors’ knowledge no study to date has ...comprehensively examined associations between transplantation status and mortality after a cancer diagnosis.
Methods
The authors assessed cases in the US general population (N=7,147,476) for 16 different cancer types as ascertained from 11 cancer registries. The presence of a solid organ transplant prior to diagnosis (N=11,416 cancer cases) was identified through linkage with the national transplantation registry (1987‐2014). Cox models were used to examine the association between transplantation status and cancer‐specific mortality, adjusting for demographic characteristics and cancer stage.
Results
For the majority of cancers, cancer‐specific mortality was higher in transplant recipients compared with other patients with cancer. The increase was particularly pronounced for melanoma (adjusted hazard ratio aHR, 2.59; 95% confidence interval 95% CI, 2.18‐3.00) and cancers of the breast (aHR, 1.88; 95% CI, 1.61‐2.19), bladder (aHR, 1.85; 95% CI, 1.58‐2.17), and colorectum (aHR, 1.77; 95% CI, 1.60‐1.96), but it also was increased for cancers of the oral cavity/pharynx, stomach, pancreas, kidney, and lung as well as diffuse large B‐cell lymphoma (aHR range, 1.21‐1.47). Associations remained significant after adjustment for first‐course cancer treatment and generally were stronger among patients with local‐stage cancers for whom potentially curative treatment was provided, including patients with melanoma (aHR, 3.82; 95% CI, 2.94‐4.97) and cancers of the colorectum (aHR, 2.77; 95% CI, 2.07‐3.70), breast (aHR, 2.08; 95% CI, 1.50‐2.88), and prostate (aHR, 1.60; 95% CI, 1.12‐2.29), despite the lack of an association for prostate cancer overall.
Conclusions
For multiple cancer types, transplant recipients with cancer appear to have an elevated risk of dying of their cancer, even after adjustment for stage and treatment, which may be due to impaired immunity.
The number of solid organ transplant recipients has increased within the last 10 years, with nearly 35,000 transplantations reported to have occurred in the United States in 2017. Although solid organ transplantation is life‐saving, recipients have an elevated risk of many types of cancer, and for multiple cancer types, transplant recipients with cancer appear to have an elevated risk of dying of their cancer, even after adjustment for stage of disease and treatment, which may be due to impaired immunity.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Inorganic arsenic is a toxic naturally occurring element in soil and water in many regions of the US including the Midwest. Prostate cancer is the second most common type of cancer in men in Iowa, ...surpassed only by non-melanotic skin cancer. Epidemiology studies have evaluated arsenic exposure from drinking water and prostate cancer, but most have focused on high-level exposures outside the US. As drinking water from groundwater sources is a major source of arsenic exposure, we conducted an ecologic study to evaluate prostate cancer and arsenic in drinking water from public water sources and private wells in Iowa, where exposure levels are low, but duration of exposure can be long.
Arsenic data from public water systems were obtained from the Iowa Safe Drinking Water Information System for the years 1994–2003 and for private wells from two Iowa Well Water Studies, the Iowa Community Private Well Study (ICPWS, 2002–2003) and Iowa Statewide Rural Well Water Survey Phase 2 (SWIRL2, 2006–2008) that provided data for 87 Iowa counties. Prostate cancer incidence data from 2009 to 2013 for Iowa were obtained from Surveillance, Epidemiology and End Results’ SEER*Stat software. County averages of water arsenic levels varied from 1.08 to 18.6 ppb, with three counties above the current 10 ppb limit. Based on the tertiles of arsenic levels, counties were divided into three groups: low (1.08–2.06 ppb), medium (2.07–2.98 ppb), and high (2.99–18.6 ppb).
Spatial Poisson regression modeling was conducted to estimate the risk ratios (RR) of prostate cancer by tertiles of arsenic level at a county level, adjusted for demographic and risk factors. The RR of prostate cancer were 1.23 (95% CI, 1.16–1.30) and 1.28 (95% CI, 1.21–1.35) in the medium and high groups, respectively, compared to the low group after adjusting for risk factors. The RR increased to 1.36 (95% CI, 1.28–1.45) in the high group when analyses were restricted to aggressive prostate cancers (Gleason score ≥ 7). This study shows a significant dose-dependent association between low-level arsenic exposure and prostate cancer, and if this result is replicated in future individual-level studies, may suggest that 10 ppb is not protective for human health.
•Arsenic data for Iowa public water sources and private well water were analyzed.•Counties grouped in tertiles: 1.08–2.06 ppb, 2.07–2.98 ppb, 2.99–18.59 ppb arsenic.•Risk ratios (RR) for prostate cancer were 1.23 (median), 1.28 (high arsenic group).•For aggressive cancers the high arsenic group RR increased to 1.36 (CI 1.28–1.45).•If findings are confirmed, stricter arsenic limits in drinking water may be needed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
This study sought to determine the prevaccine type-specific prevalence of human papillomavirus (HPV)-associated cancers in the United States to evaluate the potential impact of the HPV types in the ...current and newly approved 9-valent HPV vaccines.
The Centers for Disease Control and Prevention partnered with seven US population-based cancer registries to obtain archival tissue for cancers diagnosed from 1993 to 2005. HPV testing was performed on 2670 case patients that were fairly representative of all participating cancer registry cases by age and sex. Demographic and clinical data were evaluated by anatomic site and HPV status. Current US cancer registry data and the detection of HPV types were used to estimate the number of cancers potentially preventable through vaccination.
HPV DNA was detected in 90.6% of cervical, 91.1% of anal, 75.0% of vaginal, 70.1% of oropharyngeal, 68.8% of vulvar, 63.3% of penile, 32.0% of oral cavity, and 20.9% of laryngeal cancers, as well as in 98.8% of cervical cancer in situ (CCIS). A vaccine targeting HPV 16/18 potentially prevents the majority of invasive cervical (66.2%), anal (79.4%), oropharyngeal (60.2%), and vaginal (55.1%) cancers, as well as many penile (47.9%), vulvar (48.6%) cancers: 24 858 cases annually. The 9-valent vaccine also targeting HPV 31/33/45/52/58 may prevent an additional 4.2% to 18.3% of cancers: 3944 cases annually. For most cancers, younger age at diagnosis was associated with higher HPV 16/18 prevalence. With the exception of oropharyngeal cancers and CCIS, HPV 16/18 prevalence was similar across racial/ethnic groups.
In the United States, current vaccines will reduce most HPV-associated cancers; a smaller additional reduction would be contributed by the new 9-valent vaccine.
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