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Background Perceived discrimination in health care settings can have adverse consequences on mental health in minority groups. However, the association between perceived discrimination and mental health is prone to unmeasured confounding. The study aims to quantitatively evaluate the influence of unmeasured confounding in this association, using g-estimation. Methods In a predominantly African American cohort, we applied g-estimation to estimate the association between perceived discrimination and mental health, adjusted and unadjusted for measured confounders. Mental health was measured using clinical diagnoses of anxiety, depression and bipolar disorder. Perceived discrimination was measured as the number of patient-reported discrimination events in health care settings. Measured confounders included demographic, socioeconomic, residential and health characteristics. The influence of confounding was denoted as α 1 from g-estimation. We compared α 1 for measured and unmeasured confounding. Results Strong associations between perceived discrimination in health care settings and mental health outcomes were observed. For anxiety, the odds ratio (95% confidence interval) unadjusted and adjusted for measured confounders were 1.30 (1.21, 1.39) and 1.26 (1.17, 1.36), respectively. The α 1 for measured confounding was –0.066. Unmeasured confounding with α 1 = 0.200 ⁠ , which was over three times that of measured confounding, corresponds to an odds ratio of 1.12 (1.01, 1.24). Similar results were observed for other mental health outcomes. Conclusion Compared with measured confounding, unmeasured that was three times measured confounding was not enough to explain away the association between perceived discrimination and mental health, suggesting that this association is robust to unmeasured confounding. This study provides a novel framework to quantitatively evaluate unmeasured confounding. [ABSTRACT FROM AUTHOR]

Objectives: To examine whether long-term air pollution exposure is associated with central hemodynamic and brachial artery stiffness parameters. Methods: We assessed central hemodynamic parameters including central blood pressure, cardiac parameters, systemic vascular compliance and resistance, and brachial artery stiffness measures [including brachial artery distensibility (BAD), compliance (BAC), and resistance (BAR)] using waveform analysis of the arterial pressure signals obtained from a standard cuff sphygmomanometer (DynaPulse2000A, San Diego, CA). The long-term exposures to particles with an aerodynamic diameter < 2.5 μm (PM2.5) and nitrogen dioxide (NO2) for the 3-year periods prior to enrollment were estimated at residential addresses using fine-scale intra-urban spatiotemporal models. Linear mixed models adjusted for potential confounders were used to examine associations between air pollution exposures and health outcomes. Results: The cross-sectional study included 2,387 Chicago residents (76% African Americans) enrolled in the ChicagO Multiethnic Prevention And Surveillance Study (COMPASS) during 2013–2018 with validated address information, PM2.5 or NO2, key covariates, and hemodynamics measurements. We observed long-term concentrations of PM2.5 and NO2 to be positively associated with central systolic, pulse pressure and BAR, and negatively associated with BAD, and BAC after adjusting for relevant covariates. A 1-µg/m3 increment in preceding 3-year exposures to PM2.5 was associated with 1.8 mmHg higher central systolic (95% CI: 0.98, 4.16), 1.0 mmHg higher central pulse pressure (95% CI: 0.42, 2.87), a 0.56%mmHg lower BAD (95% CI: -0.81, -0.30), and a 0.009 mL/mmHg lower BAC (95% CI: -0.01, -0.01). Conclusion: This population-based study provides evidence that long-term exposures to PM2.5 and NO2 is related to central BP and arterial stiffness parameters, especially among African Americans. [ABSTRACT FROM AUTHOR]

Introduction: The NIH All of Us Research Program has enrolled over 544,000 participants across the US with unprecedented racial/ethnic diversity, offering opportunities to investigate myriad exposures and diseases. This paper aims to investigate the association between PM2.5 exposure and cancer risks. Materials and methods: This work was performed on data from 409,876 All of Us Research Program participants using the All of Us Researcher Workbench. Cancer case ascertainment was performed using data from electronic health records and the self-reported Personal Medical History questionnaire. PM2.5 exposure was retrieved from NASA's Earth Observing System Data and Information Center and assigned using participants' 3-digit zip code prefixes. Multivariate logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI). Generalized additive models (GAMs) were used to investigate non-linear relationships. Results: A total of 33,387 participants and 46,176 prevalent cancer cases were ascertained from participant EHR data, while 20,297 cases were ascertained from self-reported survey data from 18,133 participants; 9,502 cancer cases were captured in both the EHR and survey data. Average PM2.5 level from 2007 to 2016 was 8.90 μg/m3 (min 2.56, max 15.05). In analysis of cancer cases from EHR, an increased odds for breast cancer (OR 1.17, 95% CI 1.09–1.25), endometrial cancer (OR 1.33, 95% CI 1.09–1.62) and ovarian cancer (OR 1.20, 95% CI 1.01–1.42) in the 4th quartile of exposure compared to the 1st. In GAM, higher PM2.5 concentration was associated with increased odds for blood cancer, bone cancer, brain cancer, breast cancer, colon and rectum cancer, endocrine system cancer, lung cancer, pancreatic cancer, prostate cancer, and thyroid cancer. Conclusions: We found evidence of an association of PM2.5 with breast, ovarian, and endometrial cancers. There is little to no prior evidence in the literature on the impact of PM2.5 on risk of these cancers, warranting further investigation. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the joint effect of neighborhood disadvantages on asthma prevalence and evaluate whether individual-level variables protect residents against neighborhood disadvantages. Data from the Chicago Multiethnic Prevention and Surveillance Study (from 2013–2020) were analyzed. Eight neighborhood characteristics were measured using the Chicago Health Atlas, including neighborhood unsafety, limited access to healthy food, neighborhood alienation, severe rent burden, vacant housing, single-parent household, neighborhood poverty, and unemployment. A structured questionnaire measured asthma diagnosis (childhood or adulthood) and individual-level variables including sex, age, income, education, and race. Weighted quantile sum (WQS) regression was used to evaluate the impact of neighborhood disadvantages. Stratified analysis was performed by income and education. A total of 6,592 participants (mean age = 53.5 (standard deviation, 11.1) years) were included. Most of the study population were non-Hispanic Black (82.5%) and reported an annual household income less than $15,000 (53%). Asthma prevalence was 23.6%. The WQS index, which represents the overall neighborhood disadvantages, was associated with asthma prevalence (odds ratio = 1.14, 95% confidence interval: 1.07, 1.22) when adjusted for individual-level confounders. Neighborhood poverty contributed 40.8% to the overall impact, followed by vacant housing (23.1%) and neighborhood alienation (22.9%). When stratified by individual-level income or education, no difference was observed for the association between WQS index and asthma prevalence. [ABSTRACT FROM AUTHOR]

The BRAF V600E mutation and DNA promoter methylation play important roles in the pathogenesis of thyroid cancer (TC). However, the association of these genetic and epigenetic alterations is not clear. In this study, using paired tumor and surrounding normal tissue from the same patients, on a genome-wide scale we tried to identify (a) any association between BRAF mutation and DNA promoter methylation, and (b) if the molecular findings may provide a basis for therapeutic intervention. We included 40 patients with TC (female = 28, male = 12) without distant metastasis. BRAF mutation was present in 18 cases. We identified groups of differentially methylated loci (DML) that are found in (a) both BRAF mutant and wild type, (b) only in BRAF mutant tumors, and (c) only in BRAF wild type. BRAF mutation-specific promoter loci were more frequently hypomethylated, whereas BRAF wild-type-specific loci were more frequently hypermethylated. Common DML were enriched in cancer-related pathways, including the mismatch repair pathway and Wnt-signaling pathway. Wild-type-specific DML were enriched in RAS signaling. Methylation status of checkpoint signaling genes, as well as the T-cell inflamed genes, indicated an opportunity for the potential use of PDL1 inhibitors in BRAF mutant TC. Our study shows an association between BRAF mutation and methylation in TC that may have biological significance. [ABSTRACT FROM AUTHOR]

Background: Underrepresented persons are often not included in biomedical research. It is unknown if the general Asian American population is being represented in All of Us. The purpose of this study was to compare the Asian demographic data in the All of Us cohort with the Asian nationally representative data from the American Community Survey. Method: Demographic characteristics and health literacy of Asians in All of Us were examined. Findings were qualitatively compared with the Asian data in the 2019 American Community Survey 1-year estimate. Results: Compared with the national composition of Asians, less All of Us participants were born outside the United States (64% vs 79%), were younger, and had higher levels of education (76% vs 52%). Over 60% of All of Us participants reported high levels of health literacy. Conclusion: This study had implications for the development of strategies that ensure diverse populations are represented in biomedical research. [ABSTRACT FROM AUTHOR]

Introduction: The NIH All of Us Research Program will have the scale and scope to enable research for a wide range of diseases, including cancer. The program's focus on diversity and inclusion promises a better understanding of the unequal burden of cancer. Preliminary cancer ascertainment in the All of Us cohort from two data sources (self-reported versus electronic health records (EHR)) is considered. Materials and methods: This work was performed on data collected from the All of Us Research Program's 315,297 enrolled participants to date using the Researcher Workbench, where approved researchers can access and analyze All of Us data on cancer and other diseases. Cancer case ascertainment was performed using data from EHR and self-reported surveys across key factors. Distribution of cancer types and concordance of data sources by cancer site and demographics is analyzed. Results and discussion: Data collected from 315,297 participants resulted in 13,298 cancer cases detected in the survey (in 89,261 participants), 23,520 cancer cases detected in the EHR (in 203,813 participants), and 7,123 cancer cases detected across both sources (in 62,497 participants). Key differences in survey completion by race/ethnicity impacted the makeup of cohorts when compared to cancer in the EHR and national NCI SEER data. Conclusions: This study provides key insight into cancer detection in the All of Us Research Program and points to the existing strengths and limitations of All of Us as a platform for cancer research now and in the future. [ABSTRACT FROM AUTHOR]

Objective: Tumor registries in integrated healthcare systems (IHCS) have high precision for identifying incident cancer but often miss recently diagnosed cancers or those diagnosed outside of the IHCS. We developed an algorithm using the electronic medical record (EMR) to identify people with a history of cancer not captured in the tumor registry to identify adults, aged 40-65 years, with no history of cancer.Materials and Methods: The algorithm was developed at Kaiser Permanente Colorado, and then applied to 7 other IHCS. We included tumor registry data, diagnosis and procedure codes, chemotherapy files, oncology encounters, and revenue data to develop the algorithm. Each IHCS adapted the algorithm to their EMR data and calculated sensitivity and specificity to evaluate the algorithm's performance after iterative chart review.Results: We included data from over 1.26 million eligible people across 8 IHCS; 55 601 (4.4%) were in a tumor registry, and 44848 (3.5%) had a reported cancer not captured in a registry. The common attributes of the final algorithm at each site were diagnosis and procedure codes. The sensitivity of the algorithm at each IHCS was 90.65%-100%, and the specificity was 87.91%-100%.Discussion: Relying only on tumor registry data would miss nearly half of the identified cancers. Our algorithm was robust and required only minor modifications to adapt to other EMR systems.Conclusion: This algorithm can identify cancer cases regardless of when the diagnosis occurred and may be useful for a variety of research applications or quality improvement projects around cancer care. [ABSTRACT FROM AUTHOR]

Purpose: Over the past several decades, there has been a reported increase in the incidence of thyroid cancer in many countries. We previously reported an increase in thyroid cancer incidence across continents between 1973 and 2002. Here, we provide an update on the international trends in thyroid cancer between 2003 and 2007.Methods: We examined thyroid cancer incidence data from the Cancer Incidence in Five Continents (CI5) database for the period between 1973 and 2007 from 24 populations in the Americas, Asia, Europe, Africa and Oceania, and report on the time trends as well as the distribution by histologic type and gender worldwide.Results: The incidence of thyroid cancer increased during the period from 1998-2002 to 2003-2007 in the majority of populations examined, with the highest rates observed among women, most notably in Israel and the United States SEER registry, at over 14 per 100,000 people. This update suggests that incidence is rising in a similar fashion across all regions of the world. The histologic and gender distributions in the updated CI5 are consistent with the previous report.Conclusions: Our analysis of the published CI5 data illustrates that the incidence of thyroid cancer increased between 1998-2002 and 2003-2007 in most populations worldwide, and rising rates continue in all regions of the world. [ABSTRACT FROM AUTHOR]

Objectives: Animal studies suggest that exposure to pesticides may alter thyroid function; however, few epidemiologic studies have examined this association. We evaluated the relationship between individual pesticides and thyroid function in 679 men enrolled in a substudy of the Agricultural Health Study, a cohort of licensed pesticide applicators.Methods: Self-reported lifetime pesticide use was obtained at cohort enrolment (1993-1997). Intensity-weighted lifetime days were computed for 33 pesticides, which adjusts cumulative days of pesticide use for factors that modify exposure (eg, use of personal protective equipment). Thyroid-stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3) and antithyroid peroxidase (anti-TPO) autoantibodies were measured in serum collected in 2010-2013. We used multivariate logistic regression to estimate ORs and 95% CIs for subclinical hypothyroidism (TSH >4.5 mIU/L) compared with normal TSH (0.4-<4.5 mIU/L) and for anti-TPO positivity. We also examined pesticide associations with TSH, T4 and T3 in multivariate linear regression models.Results: Higher exposure to the insecticide aldrin (third and fourth quartiles of intensity-weighted days vs no exposure) was positively associated with subclinical hypothyroidism (ORQ3=4.15, 95% CI 1.56 to 11.01, ORQ4=4.76, 95% CI 1.53 to 14.82, ptrend <0.01), higher TSH (ptrend=0.01) and lower T4 (ptrend=0.04). Higher exposure to the herbicide pendimethalin was associated with subclinical hypothyroidism (fourth quartile vs no exposure: ORQ4=2.78, 95% CI 1.30 to 5.95, ptrend=0.02), higher TSH (ptrend=0.04) and anti-TPO positivity (ptrend=0.01). The fumigant methyl bromide was inversely associated with TSH (ptrend=0.02) and positively associated with T4 (ptrend=0.01).Conclusions: Our results suggest that long-term exposure to aldrin, pendimethalin and methyl bromide may alter thyroid function among male pesticide applicators. [ABSTRACT FROM AUTHOR]

Objective: Nitrate and nitrite are probable human carcinogens when ingested under conditions that increase the formation of N-nitroso compounds. There have been limited efforts to develop US databases of dietary nitrate and nitrite for standard FFQ. Here we describe the development of a dietary nitrate and nitrite database and its calibration.Design: We analysed data from a calibration study of 1942 members of the NIH-AARP (NIH-AARP, National Institutes of Health-AARP) Diet and Health Study who reported all foods and beverages consumed on the preceding day in two non-consecutive 24 h dietary recalls (24HR) and completed an FFQ. Based on a literature review, we developed a database of nitrate and nitrite contents for foods reported on these 24HR and for food category line items on the FFQ. We calculated daily nitrate and nitrite intakes for both instruments, and used a measurement error model to compute correlation coefficients and attenuation factors for the FFQ-based intake estimates using 24HR-based values as reference data.Results: FFQ-based median nitrate intake was 68·9 and 74·1 mg/d, and nitrite intake was 1·3 and 1·0 mg/d, in men and women, respectively. These values were similar to 24HR-based intake estimates. Energy-adjusted correlation coefficients between FFQ- and 24HR-based values for men and women respectively were 0·59 and 0·57 for nitrate and 0·59 and 0·58 for nitrite; energy-adjusted attenuation factors were 0·59 and 0·57 for nitrate and 0·47 and 0·38 for nitrite.Conclusions: The performance of the FFQ in assessing dietary nitrate and nitrite intakes is comparable to that for many other macro- and micronutrients. [ABSTRACT FROM AUTHOR]

Background: Radiation is a well-described risk factor for differentiated thyroid carcinoma (DTC). Although the natural history of DTC following nuclear disasters and in healthcare workers with chronic radiation exposure (RE) has been described, little is known about DTC following short-term exposure to therapeutic medical radiation for benign disease. This study compares DTC morphology and outcomes in patients with and without a prior history of therapeutic external RE. Methods: A retrospective review was performed of patients with DTC treated at The University of Chicago between 1951 and 1987, with a median follow-up of 27 years (range 0.3-60 years). Patients were classified as either having (RE+) or not having (RE-) a history of therapeutic RE. Variables examined included sex, age at RE, dose of RE, indication for RE, DTC histology, and outcome. Morphology was determined by blinded retrospective review of all available histologic slides. Outcomes were assessed using Cox proportional hazards model and Kaplan-Meier curves. Results: Of 257 DTC patients, 165 (64%) were RE- and 92 (36%) were RE+, with males comprising a greater proportion of the RE+ group (43.5% vs. 27.3%; p = 0.01). A total of 94.2% of DTC cases were classic papillary cancers; histology did not differ between RE+ and RE- cohorts ( p = 0.73). RE was associated with an increased median overall survival (OS; 43 years vs. 38 years; hazard ratio [HR] = 0.55 [confidence interval (CI) 0.34-0.89]; p = 0.01). Survival for males in the RE- group was significantly worse than it was for RE- females (HR = 1.78 [CI 1.05-3.03]; p = 0.03) or RE+ males (HR = 2.98 [CI 1.39-6.38]; p = 0.01). Recurrence did not differ between the RE+ and RE- groups (HR = 0.85 [CI 0.52-1.41]; p = 0.54), nor did DTC-specific mortality (HR = 0.54 [CI 0.21-1.37]; p = 0.20). Conclusions: While DTC following RE has historically been considered a more aggressive variant than DTC in the absence of RE, the present data indicate that RE+ DTC is associated with better OS than RE- DTC, especially for males. Additionally, recent reports are confirmed of equivalent rates of thyroid cancer recurrence. These results warrant further investigation into the factors underlying this unexpected finding. [ABSTRACT FROM AUTHOR]

Background: Alterations in DNA methylation have been demonstrated in a variety of malignancies, including papillary thyroid cancer (PTC). The full extent of dysregulation in PTC and the downstream affected pathways remains unclear. Here we report a genome-wide analysis of PTC methylation, the dysregulation of various canonical pathways, and assess its potential as a diagnostic test. Methods: A discovery set utilized 49 PTCs and matched normal controls from The Cancer Genome Atlas. Another set of 16 PTCs and 13 normal controls were used as a replication set. Genome-wide methylation analysis was done using Illumina 450 K methylation chips. Differentially methylated loci (DML) were identified by comparing PTC and matched normal tissues. DML were defined as false-discovery rate p < 0.05 and absolute Δ β ≥ 0.2. DML were then analyzed for pathway and disease commonalities using Qiagen Ingenuity Pathway Analysis. Results: Of 485,577 CpG sites analyzed, 1226 DML were identified in our discovery and replication sets, and 1061 (86.5 %) DML showed hypomethylation when comparing tumor with normal tissue. Support vector machine classification was able to differentiate benign from malignant tissue in 107 (94.7 %) of 113 tested samples, including 15 (83.3 %) of 18 samples lacking a clearly deleterious mutation. Statistically significant associations with multiple canonical pathways, diseases, and biofunctions were observed including PI3K, PTEN, wnt/β- catenin, and p53. Conclusions: Epigenetic dysregulation of multiple canonical pathways are associated with the development of PTC. This methylation signature shows promise as a future adjunctive screening test for thyroid nodules. [ABSTRACT FROM AUTHOR]

Background: The incidence of thyroid cancer is increasing. As such, the number of survivors is rising, and it has been shown that their quality of life (QOL) is worse than expected. Using results from the North American Thyroid Cancer Survivorship Study (NATCSS), a large-scale survivorship study, we aim to compare the QOL of thyroid cancer survivors to the QOL of survivors of other types of cancer. Methods: The NATCSS assessed QOL overall and in four subcategories: physical, psychological, social, and spiritual well-being using the QOL-Cancer Survivor (QOL-CS) instrument. Studies that used the QOL-CS to evaluate survivors of other types of cancers were compared to the NATCSS findings using two-tailed t tests. Results: We compared results from NATCSS to QOL survivorship studies in colon, glioma, breast, and gynecologic cancer. The mean overall QOL in NATCSS was 5.56 (on a scale of 0-10, where 10 is the best). Overall QOL of patients with thyroid cancer was similar to that of patients with colon cancer (mean 5.20, p = 0.13), glioma (mean 5.96, p = 0.23), and gynecologic cancer (mean 5.59, p = 0.43). It was worse than patients surveyed with breast cancer (mean 6.51, p < 0.01). Conclusions: We found the self-reported QOL of thyroid cancer survivors in our study population is overall similar to or worse than that of survivors of other types of cancer surveyed with the same instrument. This should heighten awareness of the significance of a thyroid cancer diagnosis and highlights the need for further research in how to improve care for this enlarging group of patients. [ABSTRACT FROM AUTHOR]

Purpose: With the exception of papillary and follicular thyroid cancer, malignant cancers of the thyroid, parathyroid, adrenal, and endocrine pancreas are uncommon. These rare malignancies present a challenge to both the clinician and patient, because few data exist on their incidence or survival. We analyzed the incidence and survival of these rare endocrine cancers (RECs), as well as the trends in incidence over time. Methods: We used the NCI's SEER 18 database (2000-2012) to investigate incidence and survival of rare cancers of the thyroid, parathyroid, adrenal, and endocrine pancreas. Cancers were categorized using the WHO classification systems. We collected data on incidence, gender, stage, size, and survival. Time trends were evaluated from 2000-2002 to 2010-2012. Results: We identified 36 types of rare cancers in the endocrine organs captured in the SEER database. RECs of the thyroid had the highest combined incidence rate (IR 8.26), followed by pancreas (IR 3.24), adrenal (IR 2.71), and parathyroid (IR 0.41). The incidence rate for all rare endocrine organs combined increased 32.4 % during the study period. The majority of the increase was attributable to rare cancers of thyroid, which increased in not only microcarcinomas, but in all sizes. The mean 5-year survival for RECs is 59.56 % (range 2.49-100 %). Conclusions: This study is a comprehensive analysis of the incidence and survival for rare malignant endocrine cancers. There has been an increase in incidence rate of almost all RECs and their survival is low. We hope that our data will serve as a source of information for clinicians as well as bring awareness regarding these uncommon cancers. [ABSTRACT FROM AUTHOR]

Background: The prevalence of thyroid cancer survivors is rising rapidly due to the combination of an increasing incidence, high survival rates, and a young age at diagnosis. The physical and psychosocial morbidity of thyroid cancer has not been adequately described, and this study therefore sought to improve the understanding of the impact of thyroid cancer on quality of life (QoL) by conducting a large-scale survivorship study. Methods: Thyroid cancer survivors were recruited from a multicenter collaborative network of clinics, national survivorship groups, and social media. Study participants completed a validated QoL assessment tool that measures four morbidity domains: physical, psychological, social, and spiritual effects. Data were also collected on participant demographics, medical comorbidities, tumor characteristics, and treatment modalities. Results: A total of 1174 participants with thyroid cancer were recruited. Of these, 89.9% were female, with an average age of 48 years, and a mean time from diagnosis of five years. The mean overall QoL was 5.56/10, with 0 being the worst. Scores for each of the sub-domains were 5.83 for physical, 5.03 for psychological, 6.48 for social, and 5.16 for spiritual well-being. QoL scores begin to improve five years after diagnosis. Female sex, young age at diagnosis, and lower educational attainment were highly predictive of decreased QoL. Conclusion: Thyroid cancer diagnosis and treatment can result in a decreased QoL. The present findings indicate that better tools to measure and improve thyroid cancer survivor QoL are needed. The authors plan to follow-up on these findings in the near future, as enrollment and data collection are ongoing. [ABSTRACT FROM AUTHOR]

Background: Follicular thyroid carcinoma (FTC) comprises 10% of differentiated thyroid cancers. Diagnostic controversy and interobserver variability render the practical diagnosis of FTC difficult. Overall survival rates vary (46-97%). The aims of this study were to review FTC histologically at the authors' tertiary care institution and to evaluate long-term survival and recurrence. Methods: Diagnostic slides from 66 FTC cases (1965-2007) were reviewed by three pathologists from two institutions (blinded to clinical outcomes), and consensus was obtained. Patient demographics, tumor characteristics, and treatment, survival, and recurrence data were collected. Thyroid cancer-specific and recurrence-free survival were calculated by original and reclassified diagnoses. Results: Forty-seven cases (71%) were reclassified: 24 (36%) to papillary thyroid carcinoma (PTC), 18 (27%) to follicular adenoma (FA), and five (8%) to poorly differentiated carcinoma (PDC). Nineteen (29%) maintained a diagnosis of FTC. The extent of surgical resection and rates of radioiodine treatment did not differ by reclassification diagnosis. Pre-review FTC-specific survival was 83.5% and 75.1% at 10 and 20 years, respectively. Following contemporary reclassification, FTC-specific survival was 77% and 33.7% at 10 and 20 years, respectively. There were no cancer-specific deaths in the FA or PTC groups. Conclusions: Over the past 50 years, changes in our understanding of the pathogenesis, histology, and behavior of thyroid carcinoma may partially account for the changes in histologic diagnosis. Elimination of PTC and FA 'contaminants' led to decrease in survival following reclassification. Variability in histologic interpretation contributes to diagnostic challenges in follicular lesions. Histologic review of thyroid tumors for research studies is crucial, especially given the ever-changing diagnostic criteria. [ABSTRACT FROM AUTHOR]

Polybrominated diphenyl ethers (PBDEs) alter thyroid hormone homeostasis, but their relationship with thyroid cancer is unknown. To investigate whether serum concentrations of PBDE were associated with thyroid cancer, we conducted a nested, case-control study in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a large multicenter clinical trial in the United States. Cases with thyroid cancer (n = 104) were recruited from 1992 to 2001 and diagnosed through 2009, and controls (n = 208) were individually matched (2:1) to cases by race, sex, birth date (within 1 year), center, and blood collection date (within 15 days). We used gas chromatography isotope dilution high-resolution mass spectrometry to measure 10 tri- to heptabrominated diphenyl eithers in serum samples. Odds ratios and 95% confidence intervals were calculated using conditional logistic regression for lipidadjusted PBDE levels detected in more than 50% of controls and for the sum of these BDEs (∑PBDEs). We observed no significant differences between cases and controls in lipid-adjusted concentrations of ∑PBDEs (for cases, median = 12.8 ng/g lipid (interquartile range, 6.2-42.1); for controls, median = 19.4 ng/g lipid (interquartile range, 7.6-50.2)) or for individual congeners. Increasing quartiles of ∑PBDEs and 4 BDE congeners were not associated with risk of thyroid cancer (for the fourth vs. first quartile of ∑PBDEs, adjusted odd ratio = 0.62, 95% confidence interval: 0.29, 1.30; P for trend = 0.56). Our study does not support an association between exposure to PBDEs and thyroid cancer. [ABSTRACT FROM AUTHOR]

Purpose: Increasing in incidence, testicular cancer is the most commonly diagnosed cancer in young men in the USA and in Europe. We sought to determine contemporary trends in testicular cancer incidence in the USA and Europe. Methods: Testicular cancer incidence data covering the USA and Europe were extracted from the SEER-13 (SEER*Stat 8.0.1) and the EUREG databases, respectively. Trends were determined using JoinPoint 3.5.3. Results: Testicular germ cell tumor (TGCT) incidence among US males >15 years increased from 1992 (5.7/100,000) to 2009 (6.8/100,000) with a significant annual percentage change (APC: 1.1 %, p < 0.001). Seminomas were 29 % of all TGCTs in 15-26 year-olds, increasing to 78 % in those 40+ years of age. TGCT rates were highest in White men (1992: 7.5/100,000; 2009: 8.6/100,000) followed by Hispanic men (1992: 4.0/100,000; 2009: 6.3/100,000) and lowest among Asian (1992: 2.0/100,000; 2009: 2.8/100,000) and Black men (1992: 0.7/100,000; 2009: 1.7/100,000). Significantly increasing incidence rates were observed in White men (APC: 1.2 %, p < 0.001) and most prominently in Hispanic men, especially from 2002 to 2009 (APC: 5.6 %, p < 0.01). Incidence of testicular cancer increased in 15 of 19 (79 %) European countries analyzed ( p < 0.05). Denmark (13.4/100,000 man-years), Switzerland (12.7/100,000 man-years), and Norway (12.7/100,000 man-years) exhibited the highest age-standardized rates, while Spain had the greatest APC (APC = 5.5, 95 % CI 3.9-7.0 %, p < 0.001). Conclusions: Between 1992 and 2009, testicular cancer incidence in the USA and Europe continued to increase, most notably in US Hispanic, Northern European, Spanish, and younger and older populations. [ABSTRACT FROM AUTHOR]

Human fertility is a complex trait determined by gene-environment interactions in which genetic factors represent a significant component. To better understand inter-individual variability in fertility, we performed one of the first genome-wide association studies (GWAS) of common fertility phenotypes, lifetime number of pregnancies and number of children in a developing country population. The fertility phenotype data and DNA samples were obtained at baseline recruitment from individuals participating in a large prospective cohort study in Bangladesh. GWAS analyses of fertility phenotypes were conducted among 1,686 married women. One SNP on chromosome 4 was non-significantly associated with number of children at P <10-7 and number of pregnancies at P <10-6. This SNP is located in a region without a gene within 1 Mb. One SNP on chromosome 6 was non-significantly associated with extreme number of children at P <10-6. The closest gene to this SNP is HDGFL1, a hepatoma-derived growth factor. When we excluded hormonal contraceptive users, a SNP on chromosome 5 was non-significantly associated at P <10-5 for number of children and number of pregnancies. This SNP is located near C5orf64, an open reading frame, and ZSWIM6, a zinc ion binding gene. We also estimated the heritability of these phenotypes from our genotype data using GCTA (Genome-wide Complex Trait Analysis) for number of children (hg2 = 0.149, SE = 0.24, p-value = 0.265) and number of pregnancies (hg2 = 0.007, SE = 0.22, p-value = 0.487). Our genome-wide association study and heritability estimates of number of pregnancies and number of children in Bangladesh did not confer strong evidence of common variants for parity variation. However, our results suggest that future studies may want to consider the role of 3 notable SNPs in their analysis. [ABSTRACT FROM AUTHOR]

Background: Thyroid ultrasound and fine-needle aspiration (FNA) have been implicated in the overdiagnosis of thyroid cancer. To study how the use of diagnostic tools impacts thyroid cancer incidence, we propose using physician age as a surrogate. We aimed to determine whether thyroid cancer incidence is higher in areas with a high density of young physicians compared with areas with a high density of older physicians. Methods: SEER 13 database was used to determine thyroid cancer incidence. These data were linked to the Area Resource File data (2000), containing information on physician age at a county-specific level. Cohorts were divided by age based on the concentration of physicians within a population of 1,000,000 persons. The study period was divided into two time periods (1992-1995, 2006-2009). Results: The incidence of thyroid cancer was stable in areas with high concentrations of young and older physicians during the 1992-1995 time period [<35: 5.97; 55-64: 6.82; ≥65: 6.70 (per 100,000py)]. Areas with high concentrations of young physicians had an increased incidence of thyroid cancer compared with areas of high concentrations of older physicians during the 2006-2009 period [<35: 13.3; 55-64: 9.86; ≥65: 7.47 (per 100,000py)]. Conclusions: Thyroid cancer incidence was lower in areas with high concentrations of older physicians. This may be the result of increased adoption of thyroid ultrasound and FNA among younger physicians who have trained after diagnostic tools became common. Age of the diagnosing physician is a surrogate for diagnostic utility contributing to thyroid cancer trends. [ABSTRACT FROM AUTHOR]

To analyze racial, ethnic, sex and age disparities in chronic lymphocytic leukemia (CLL), we examined population-based overall survival (OS) data from Surveillance, Epidemiology, and End Results (SEER)-13 (1992-2009) across various races/ethnicities over two consecutive 9-year periods: era 1 (1992-2000) and era 2 (2001-2009). We analyzed 28 590 patients (whites: 24 438, blacks: 1954, Hispanics: 1389 and Asians/Pacific Islanders [A/PI]: 809). A higher proportion of whites were aged > 80 years (22% vs. 17% [Hispanics], 16% [blacks], 16% [A/PI]; p < 0.001). Higher socioeconomic status (SES) was also identified for A/PI and whites compared with blacks and Hispanics ( p < 0.001). OS for all patients improved at 5 years (66% vs. 60%, p < 0.0001) and was significant in all races/ethnicities except A/PI. Patients of higher SES had better outcomes than others independent of era, but both SES classes experienced relative improvement in their OS across eras. The OS of patients with CLL has improved in the modern era but racial/ethnic, gender and SES differences persist, warranting further investigation. [ABSTRACT FROM AUTHOR]

ObjectivePrevious studies examining the role of single foods or nutrients in the aetiology of non-Hodgkin lymphoma (NHL) have produced inconsistent findings. Few studies have examined associations for dietary patterns, which may more accurately reflect patterns of consumption and the complexity of dietary intake. The objective of the present study was to examine whether dietary patterns identified by factor analysis were associated with NHL risk.DesignCase–control.SettingPopulation-based sample residing in Nebraska from 1999 to 2002.SubjectsA total of 336 cases and 460 controls.ResultsFactor analysis identified two major dietary patterns: (i) a ‘Meat, Fat and Sweets’ dietary pattern characterized by high intakes of French fries, red meat, processed meat, pizza, salty snacks, sweets and desserts, and sweetened beverages; and (ii) a ‘Fruit, Vegetables and Starch’ dietary pattern characterized by high intakes of vegetables, fruit, fish, and cereals and starches. In multivariable logistic regression models, the ‘Meat, Fat and Sweets’ dietary pattern was associated with an increased risk of overall NHL (ORQ4v.Q1 = 3·6, 95 % CI 1·9, 6·8; Ptrend = 0·0004), follicular lymphoma (ORQ4v.Q1 = 3·1, 95 % CI 1·2, 8·0; Ptrend = 0·01), diffuse large B-cell lymphoma (ORQ4v.Q1 = 3·2, 95 % CI 1·1, 9·0; Ptrend = 0·09) and marginal zone lymphoma (ORQ4v.Q1 = 8·2, 95 % CI 1·3, 51·2; Ptrend = 0·05). No association with overall or subtype-specific risk was detected for the ‘Fruit, Vegetables and Starch’ dietary pattern. No evidence of heterogeneity was detected across strata of age, sex, BMI, smoking status or alcohol consumption.ConclusionsOur results suggest that a dietary pattern high in meats, fats and sweets may be associated with an increased risk of NHL. [ABSTRACT FROM PUBLISHER]

Nitrate and nitrite are precursors of endogenously formed N-nitroso compounds (NOC), known animal carcinogens. Nitrosation reactions forming NOCs can be inhibited by vitamin C and other antioxidants. We prospectively investigated the association between dietary nitrate and nitrite intake and risk of colorectal cancer in the Shanghai Women's Health Study, a cohort of 73,118 women ages 40-70 residing in Shanghai. We evaluated effect modification by factors that affect endogenous formation of NOCs: vitamin C (at or above/below median) and red meat intake (at or above/below median). Nitrate, nitrite and other dietary intakes were estimated from a 77-item food frequency questionnaire administered at baseline. Over a mean of 11 years of follow-up, we identified 619 colorectal cancer cases ( n = 383, colon; n = 236, rectum). Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazard regression. Overall, nitrate intake was not associated with colorectal cancer risk (HR = 1.08; 95% CI: 0.73-1.59). However, among women with vitamin C intake below the median (83.9 mg day−1) and hence higher potential exposure to NOCs, risk of colorectal cancer increased with increasing quintiles of nitrate intake (highest vs. lowest quintile HR = 2.45; 95% CI: 1.15-5.18; p trend = 0.02). There was no association among women with higher vitamin C intake. We found no association between nitrite intake and risk of colorectal cancer overall or by intake level of vitamin C. Our findings suggest that high dietary nitrate intake among subgroups expected to have higher exposure to endogenously formed NOCs increases risk of colorectal cancer. [ABSTRACT FROM AUTHOR]

Numerous occupational and environmental exposures have been shown to disrupt thyroid hormones, but much less is known about their relationships with thyroid cancer. Here we review the epidemiology studies of occupations and occupational exposures and thyroid cancer incidence to provide insight into preventable risk factors for thyroid cancer. The published literature was searched using the Web of Knowledge database for all articles through August 2013 that had in their text 'occupation' 'job' 'employment' or 'work' and 'thyroid cancer'. After excluding 10 mortality studies and 4 studies with less than 5 exposed incident cases, we summarised the findings of 30 articles that examined thyroid cancer incidence in relation to occupations or occupational exposure. The studies were grouped by exposure/occupation category, study design and exposure assessment approach. Where available, gender-stratified results are reported. The most studied (19 of 30 studies) and the most consistent associations were observed for radiation-exposed workers and healthcare occupations. Suggestive, but inconsistent, associations were observed in studies of pesticide-exposed workers and agricultural occupations. Findings for other exposures and occupation groups were largely null. The majority of studies had few exposed cases and assessed exposure based on occupation or industry category, self-report, or generic (population-based) job exposure matrices. The suggestive, but inconsistent findings for many of the occupational exposures reviewed here indicate that more studies with larger numbers of cases and better exposure assessment are necessary, particularly for exposures known to disrupt thyroid homeostasis. [ABSTRACT FROM AUTHOR]

In a cohort of 301 patients with non-Hodgkin lymphoma (NHL), we examined whether the pre-diagnostic consumption of fruits and vegetables, or of nutrients concentrated in fruits and vegetables, was associated with overall survival (OS). Proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality. A total of 91 deaths occurred in the patient cohort over a median follow-up period of 8.2 years. No association with OS was detected for a dietary pattern characterized by high intakes of fruits, vegetables and starch; fruit intake; vegetable intake; or nutrient intake in patients diagnosed with overall NHL, follicular lymphoma or diffuse large B-cell lymphoma. Higher intakes of carotene-rich vegetables (HR = 0.4 [0.2-1.0]; ptrend = 0.05) and α-carotene (HRT3 vs. T1 = 0.4 [0.2-0.9]; ptrend = 0.03) were associated with better OS among ever smokers. Overall, our data suggest that the intake of fruits and vegetables prior to diagnosis is not associated with OS in patients with NHL. [ABSTRACT FROM AUTHOR]

We examined whether smoking prior to non-Hodgkin lymphoma ( NHL) diagnosis was associated with overall survival ( OS) and conducted a meta-analysis to assess the evidence relating pre-diagnosis cigarette smoking with OS. Among 523 NHL patients, worse OS was suggested for greater pre-diagnostic smoking habits when compared to never smokers. In the meta-analysis ( n = 5 patient populations), inferior OS was observed for greater number of cigarettes smoked per day, years of cigarette smoking, and pack-years of cigarette smoking. The inferior survival was more pronounced for follicular than for diffuse large B cell lymphoma. Pre-diagnosis cigarette smoking may adversely impact the survival of NHL patients. [ABSTRACT FROM AUTHOR]

Background: The increases in thyroid cancer overall and in the predominant papillary type have been well documented, but trends for follicular thyroid cancer, a less common but more aggressive variant, have not been as well characterized. In this study, we determined the incidence patterns for follicular thyroid cancer and compared trends between the follicular and papillary thyroid cancers in the United States. Methods: We used the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program to examine incidence in the United States during 1980-2009, stratified by demographic and tumor characteristics. Incidence rates (IR) were calculated, relative risks were expressed as incidence rate ratios (IRR), and temporal trends were expressed as percentage changes and plotted. Results: Overall we observed a modest increase in age-adjusted follicular thyroid cancer rates among women (31.89%) and men (35.88%). Rates increased most dramatically for regional stage tumors compared to localized tumors in women, whereas the rates for all tumor sizes rose. These findings reveal increases in more aggressive tumors in women in addition to small and localized tumors. The trends for males were different from those among females. Among males, the largest increase was observed for regional and smaller size tumors. The papillary-to-follicular IRR overall was 7.07 [95% confidence interval 6.91-7.24], which varied from 7.37 among Whites to 3.86 among Blacks (SEER race/ethnicity categories), and increased significantly from 3.98 during 1980-1984 to 9.88 during 2005-2009. Conclusion: The different trends for follicular and papillary types of thyroid cancer illustrate that thyroid cancer is a heterogeneous disease. Our results do not support the hypothesis that increasing thyroid cancer rates are largely due to improvements in detection, and suggest the importance of evaluating thyroid cancer types separately in future studies. [ABSTRACT FROM AUTHOR]

Although an increased incidence of mantle cell lymphoma (MCL) has been reported, age-specific incidence patterns have not been described. Further analyses could inform investigation into the etiology of this disease. We conducted an epidemiologic study using the 13 Surveillance, Epidemiology, and End Results (SEER) registries to evaluate MCL incidence from 1992 through 2009. We calculated the proportional changes in the incidence of MCL for subpopulations defined by age, race/ethnicity and gender over time and the racial/ethnic and gender disparities. We observed a 130.9% increase in MCL incidence from 1992-1994 to 2005-2009. The increase was strongest for males (199.0%) and for whites (153.0%). The incidence increased 161%, 200%, 398% and 429% from 1992-1994 to 2005-2009 in white men ages 50-59, 60-69, 70-79 and 80+, respectively, whereas the increase in white females was 86%, 82%, 50% and 193% in the corresponding age groups. We observed a male-to-female incidence rate ratio (IRR) of 2.65 and a white-to-black IRR of 2.21. Our analysis confirmed significant increases in MCL, and illustrated that the incidence is increasing more rapidly in elderly persons, particularly in white males. We also identified novel age-specific temporal trends by race/ethnicity and sex. In addition, we found that the gender and white-to-black disparities have grown over time. Our findings may impact MCL etiologic investigation and treatment research. [ABSTRACT FROM AUTHOR]

Background: Reports of similar age-specific incidence rates and a female-to-male gender disparity by racial/ethnic groups suggests that further consideration of race-specific patterns may confer insight into the possible causes of thyroid cancer or explanations for the increase in incidence. Methods: We used the National Cancer Institute's (NCIs) surveillance, epidemiology, and end results (SEER) program and Joinpoint Regression for cases diagnosed during 1992-2009 to investigate trends and rates of acceleration for papillary thyroid cancer by gender and race/ethnicity. Results: We determined the annual percent change (APC) and found a yearly increase of 7.0 % for papillary thyroid cancer for the most recent APC trend, with an APC of 6.3 and 7.1 % for white males and females, respectively; an APC of 4.3 and 8.4 % for black males and females, respectively; an APC of 4.2 and 6.7 % for Hispanic males and females, respectively; and an APC of 3.4 and 6.4 % in Asian/PI males and females, respectively. The APC projections show the rates of papillary thyroid cancer rising in males, but the patterns are more dramatic in females, with rates of papillary thyroid cancer in females surpassing rates of common cancers and becoming the third most common cancer in women of all ages by 2019. Conclusions: Although the lowest rates of thyroid cancer are observed in blacks, the greatest rate of acceleration is occurring in black females. Our data also show that the rate of papillary thyroid cancer will continue to surpass rates of ovarian cancer, and in white women: it is projected to be more incident than colorectal cancer as well; and in Hispanic and Asian/Pacific Islander women, rates of papillary thyroid cancer are projected to be higher than lung, colorectal, and ovarian cancers in the near future. [ABSTRACT FROM AUTHOR]

Background: Thyroid cancer incidence has risen steadily over the last few decades in most of the developed world, but information on incidence trends in developing countries is limited. Sao Paulo, Brazil, has one of the highest rates of thyroid cancer worldwide, higher than in the United States. We examined thyroid cancer incidence patterns using data from the Sao Paulo Cancer Registry (SPCR) in Brazil and the National Cancer Institute's Surveillance Epidemiology End Results (SEER) program in the United States. Methods: Data on thyroid cancer cases diagnosed during 1997-2008 were obtained from SPCR ( n=15,892) and SEER ( n=42,717). Age-adjusted and age-specific rates were calculated by sex and histology and temporal patterns were compared between the two populations. Results: Overall incidence rates increased over time in both populations and were higher in Sao Paulo than in the United States among females (SPCR/SEER incidence rate ratio [IRR]=1.65) and males (IRR=1.23). Papillary was the most common histology in both populations, followed by follicular and medullary carcinomas. Incidence rates by histology were consistently higher in Sao Paulo than in the United States, with the greatest differences for follicular (IRR=2.44) and medullary (IRR=3.29) carcinomas among females. The overall female/male IRR was higher in Sao Paulo (IRR=4.17) than in SEER (IRR=3.10) and did not change over time. Papillary rates rose over time more rapidly in Sao Paulo (annual percentage change=10.3% among females and 9.6% among males) than in the United States (6.9% and 5.7%, respectively). Regardless of sex, rates rose faster among younger people (<50 years) in Sao Paulo, but among older people (≥50 years) in the United States. The papillary to follicular carcinoma ratio rose from <3 to >8 among both Sao Paulo males and females, in contrast to increases from 9 to 12 and from 6 to 7 among U.S.males and females, respectively. Conclusions: Increased diagnostic activity may be contributing to the notable rise in incidence, mainly for papillary type, in both populations, but it is not likely to be the only reason. Differences in iodine nutrition status between Sao Paulo and the U.S. SEER population might have affected the observed incidence patterns. [ABSTRACT FROM AUTHOR]

Although established risk factors such as immunodeficiency and viral infections may be responsible for a portion of cases of non-Hodgkin lymphoma (NHL), the vast majority of cases of NHL remain unexplained. The role of dietary nitrate and nitrite in NHL risk is of interest since they are precursors of N-nitroso compounds, and nitrosoureas have been shown to induce B- and T-cell lymphomas in animal studies. However, few studies have evaluated the potential association between consumption of nitrate and nitrite and NHL by subtype or chromosomal translocation status, and the results of these studies have been inconsistent. We estimated the dietary intake of nitrate and nitrite using a food frequency questionnaire in a population-based, case-control study of 348 cases and 470 controls conducted in Nebraska in 1999-2002. A non-significant excess risk of NHL was found among women who reported an intake of nitrite in the highest quartile compared to the lowest quartile (odds ratio [OR] = 1.6; 95% confidence interval [CI]: 0.8-2.9), particularly nitrite from animal sources (OR = 1.9; 95% CI: 1.0-3.4). No significant associations were observed for nitrate or nitrite by NHL subtype. Although there were some increases in risk that support the N-nitroso hypothesis, they were not significant and do not confer strong evidence of an association. [ABSTRACT FROM AUTHOR]

Nitrate and nitrite are precursors in the endogenous formation of N-nitroso compounds and nitrate can disrupt thyroid homeostasis by inhibiting iodide uptake. We evaluated nitrate and nitrite intake and risk of thyroid cancer in the Shanghai Women's Health Study that included 73,317 women, aged 40-70 years enrolled in 1996-2000. Dietary intake was assessed at baseline using a food frequency questionnaire. During approximately 11 years of follow-up, 164 incident thyroid cancer cases with complete dietary information were identified. We used Cox proportional hazards regression to estimate relative risks (RRs). We determined the nitrate and nitrite contents of foods using values from the published literature and focusing on regional values for Chinese foods. Nitrate intake was not associated with thyroid cancer risk [RRQ4 = 0.93; 95% confidence interval (CI): 0.42-2.07; p for trend = 0.40]. Compared to the lowest quartile, women with the highest dietary nitrite intake had about a twofold risk of thyroid cancer (RRQ4 = 2.05; 95%CI: 1.20-3.51), but there was not a monotonic trend with increasing intake ( p for trend = 0.36). The trend with increasing nitrite intake from animal sources was significant ( p for trend = 0.02) and was stronger for nitrite from processed meats (RRQ4 = 1.96; 95%CI: 1.28-2.99; p for trend < 0.01). Although we did not observe an association for nitrate as hypothesized, our results suggest that women consuming higher levels of nitrite from animal sources, particularly from processed meat, may have an increased risk of thyroid cancer. [ABSTRACT FROM AUTHOR]

Greater consumption of red meat, processed meat and dairy products has been associated with an increased risk of non-Hodgkin lymphoma (NHL) in several previous reports. Phytanic acid, a saturated fatty acid obtained primarily through the consumption of ruminant meat and dairy products, may offer a potential underlying mechanism for these associations. In a population-based case–control study of 336 cases and 460 controls conducted in Nebraska during 1999–2002, we examined whether phytanic acid-containing foods or total phytanic acid intake, estimated from a food frequency questionnaire and the published phytanic acid values of 151 food items, were associated with increased NHL risk. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals for overall NHL and the common NHL histologic subtypes. In multivariable models, higher intakes of density-adjusted beef [ORT3 vs. T1 = 1.5 (1.1–2.2); Ptrend = 0.02], total dairy products [OR = 1.5 (1.1–2.2); Ptrend = 0.02) and milk [OR = 1.6 (1.1–2.3); Ptrend = 0.01] were associated with an increased risk of NHL. Intake of total phytanic acid was positively associated with NHL risk [OR = 1.5 (1.0–2.1); Ptrend = 0.04]. In analyses stratified by NHL subtype, greater consumption of beef was associated with an increased risk of diffuse large B-cell lymphoma, and greater consumption of milk was associated with an increased risk of follicular lymphoma (FL). Total phytanic acid intake was associated with an increased risk of FL and small lymphocytic lymphoma/chronic lymphocytic leukemia. Our results provide support that total phytanic acid and phytanic acid-containing foods may increase NHL risk. [ABSTRACT FROM PUBLISHER]

Relationships are unclear between polymorphisms in genes involved in metabolism and detoxification of various chemicals and papillary thyroid cancer (PTC) risk as well as their potential modification by alcohol or tobacco intake. We evaluated associations between 1647 tagging single nucleotide polymorphisms (SNPs) in 132 candidate genes/regions involved in metabolism of exogenous and endogenous compounds (Phase I/II, oxidative stress, and metal binding pathways) and PTC risk in 344 PTC cases and 452 controls. For 15 selected regions and their respective SNPs, we also assessed interaction with alcohol and tobacco use. Logistic regression models were used to evaluate the main effect of SNPs (Ptrend) and interaction with alcohol/tobacco intake. Gene- and pathway-level associations and interactions (Pgene interaction) were evaluated by combining Ptrend values using the adaptive rank-truncated product method. While we found associations between PTC risk and nine SNPs (Ptrend≤0.01) and seven genes/regions (Pregion0.05), none remained significant after correction for the false discovery rate. We found a significant interaction between UGT2B7 and NAT1 genes and alcohol intake (Pgene interaction=0.01 and 0.02 respectively) and between the CYP26B1 gene and tobacco intake (Pgene interaction=0.02). Our results are suggestive of interaction between the genetic polymorphisms in several detoxification genes and alcohol or tobacco intake on risk of PTC. Larger studies with improved exposure assessment should address potential modification of PTC risk by alcohol and tobacco intake to confirm or refute our findings. [ABSTRACT FROM AUTHOR]

Nitrate and nitrite are precursors in the formation of N-nitroso compounds. We recently found a 40% increased risk of NHL with higher dietary nitrite intake and significant increases in risk for follicular and T-cell lymphoma. It is possible that these compounds also affect NHL prognosis by enhancing cancer progression in addition to development by further impairing immune system function. To test the hypothesis that nitrate and nitrite intake affects NHL survival, we evaluated the association in study participants that have been followed post-disease diagnosis in a population-based case-control study among women in Connecticut. We did not observe a significant increasing trend of mortality for NHL overall or by subtype for nitrate or nitrite intake for deaths from NHL or death from any cause, although a borderline significant protective trend was observed for follicular lymphoma with increasing nitrate intake. We did not identify a difference in overall survival for nitrate (P = 0.39) or for nitrite (P = 0.66) or for NHL specific survival for nitrate (P = 0.96) or nitrite (P = 0.17). Thus, our null findings do not confer support for the possibility that dietary nitrate and nitrite intake impacts NHL survival by promoting immune unresponsiveness. [ABSTRACT FROM AUTHOR]

Introduction: Cytokines play a critical role in regulating the immune system. In the tumor microenvironment, they influence survival, proliferation, differentiation, and movement of both tumor and stromal cells, and regulate tumor interactions with the extracellular matrix. Given these biologic properties, there is reason to hypothesize that cytokine activity influences the pathogenesis of non-Hodgkin lymphoma (NHL). Methods: We investigated the effect of genetic variation in cytokine genes on NHL prognosis and survival by evaluating genetic variation in individual SNPs as well as the combined effect of multiple deleterious genotypes. Survival information from 496 female incident NHL cases diagnosed during 1996-2000 in Connecticut were abstracted from Connecticut Tumor Registry in 2008. Survival analyses were conducted by comparing Kaplan-Meier curves and hazard ratios (HR) were computed using Cox proportional hazard models adjusting for demographic and tumor characteristics for genes that were suggested by previous studies to be associated with NHL survival. Results: We found that the variant IL6 genotype is significantly associated (HR = 0.42; 95%CI: 0.23-0.77) with a decreased risk of death, as well as relapse and secondary cancer occurrence, among those with NHL. We also found that risk of death, relapse, and secondary cancers varied by specific SNPs for the follicular, DLBCL, and CLL/SLL histologic types. We identified combinations of polymorphisms whose combined deleterious effect significantly alter overall NHL survival and disease-free survival. Conclusion: Our study provides evidence that the identification of genetic polymorphisms in cytokine genes may help improve the prediction of NHL survival and prognosis. [ABSTRACT FROM AUTHOR]

The availability of tobacco and alcohol products in community pharmacies contradicts the pharmacists' Code of Ethics and presents challenges for a profession that is overwhelmingly not in favor of the sale of these products in its practice settings. The primary aim of this study was to estimate the proportion of pharmacies that sell tobacco products and/or alcoholic beverages and to characterize promotion of these products. The proportion of pharmacies that sell non-prescription nicotine replacement therapy (NRT) products as aids to smoking cessation also was estimated. Among 250 randomly-selected community pharmacies in Los Angeles, 32.8% sold cigarettes, and 26.0% sold alcohol products. Cigarettes were more likely to be available in traditional chain pharmacies and grocery stores than in independently-owned pharmacies (100% versus 10.8%; P < 0.001), and traditional chain drug stores and grocery stores were more likely to sell alcoholic beverages than were independently-owned pharmacies (87.5% vs. 5.4%; P < 0.001). Thirty-four (41.5%) of the 82 pharmacies that sold cigarettes and 47 (72.3%) of the 65 pharmacies that sold alcohol also displayed promotional materials for these products. NRT products were merchandised by 58% of pharmacies. Results of this study suggest that when given a choice, pharmacists choose not to sell tobacco or alcohol products. [ABSTRACT FROM AUTHOR]

Background: Nitrate is a widespread contaminant of drinking water supplies, especially in agricultural areas. Nitrate intake from drinking water and dietary sources can interfere with the uptake of iodide by the thyroid, thus potentially impacting thyroid function. Methods: We assessed the relation of estimated nitrate levels in well water supplies with thyroid health in a cohort of 2,543 Old Order Amish residing in Lancaster, Chester, and Lebanon counties in Pennsylvania for whom thyroid stimulating hormone (TSH) levels were measured during 1995-2008. Nitrate measurement data (1976-2006) for 3,613 wells in the study area were obtained from the U.S. Geological Survey and we used these data to estimate concentrations at study participants' residences using a standard linear mixed effects model that included hydrogeological covariates and kriging of the wells' residuals. Nitrate levels estimated by the model ranged from 0.35 mg/L to 16.4 mg/L N-NO3 -, with a median value of 6.5 mg/L, which was used as the cutpoint to define high and low nitrate exposure. In a validation analysis of the model, we calculated that the sensitivity of the model was 67% and the specificity was 93%. TSH levels were used to define the following outcomes: clinical hyperthyroidism (n = 10), clinical hypothyroidism (n = 56), subclinical hyperthyroidism (n = 25), and subclinical hypothyroidism (n = 228). Results: In women, high nitrate exposure was significantly associated with subclinical hypothyroidism (OR = 1.60; 95% CI: 1.11-2.32). Nitrate was not associated with subclinical thyroid disease in men or with clinical thyroid disease in men or women. Conclusions: Although these data do not provide strong support for an association between nitrate in drinking water and thyroid health, our results do suggest that further exploration of this hypothesis is warranted using studies that incorporate individual measures of both dietary and drinking water nitrate intake. [ABSTRACT FROM AUTHOR]

Introduction: Evidence from previous studies has suggested there may be physical and mental changes in health among testicular cancer survivors. No studies have been conducted in the United States, however. Methods: Study participants were initially enrolled in the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) study between 2002 and 2005. A total of 246 TGCT (testicular germ cell tumor) cases and 236 non-testicular cancer controls participated in the current study, and completed a self-administered questionnaire. Mean time since diagnosis for cases was 14 years, and no less than five for all cases. Component scores determined from responses to questions about physical and mental health on SF36 were tabulated to yield two summary measures, physical component scores (PCS), and mental component scores (MCS). Component and summary scores were normalized to a score of 50 with a standard deviation of 10 by a linear T-score transformation. Results: Overall, cases may not suffer greatly in different quality of life than controls. When all cases and controls are compared, TGCT cases had lower PCS (mean: 51.9 95% CI: 50.6-53.2, P value: 0.037) than controls (mean: 53.6 95% CI: 52.7-54.6). MCS were not significantly different ( P value: 0.091). In multivariate analyses, several physical health components were worse for TGCT cases such as role-physical (OR 1.19, 95% CI: 1.01-1.39) and general health (OR 1.26, 95% CI: 1.07-1.49) compared to controls. However, TGCT cases treated with chemotherapy had lower PCS (cases: 50.2, 95% CI: 47.6-52.8; controls: 53.6, 95% CI: 52.7-54.6, P value: 0.0032) and MCS (cases: 49.3, 95% CI: 46.5-52.1; controls: 52.0, 95% CI: 50.9-53.2, P value: 0.039). TGCT cases who received treatments other than chemotherapy did not differ from controls in either PCS or MCS. Discussion: Physical and general health limitations may affect testicular cancer survivors. Men treated with chemotherapy, however, may be most likely to suffer adverse health outcomes due to a combination of body-wide effects on physical and mental factors which affect various aspects of physical health, mental health, and overall quality of life. And in particular, physical functioning, role-physical, and general health are strongly affected. [ABSTRACT FROM AUTHOR]