Additional Years Of Follow-up Research Articles

Increased late mortality in underweight survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.

110 Background: Approximately one-in-ten adult survivors of childhood cancer are underweight. While the consequences of being overweight or obese have been well-described, outcomes among underweight childhood cancer survivors are unknown. Methods: Underweight was defined as a body mass index (BMI)< 18.5 kg/m2, calculated from self-reported height and weight on either the baseline or the first follow-up questionnaire from the Childhood Cancer Survivor Study (CCSS). National Death Index provided death data and self-reported subsequent malignant neoplasm were validated by pathology report. Chi-square test was used to examine the association between underweight status (< 8.5 kg/m2 vs ≥ 18.5 kg/m2) and baseline demographic characteristics. Marginal models with generalized estimating equations were used to evaluate the associations between BMI and outcomes. Results: Of 9454 survivors (median age 35 years old, range 17-58, with an average of 17.5 years from diagnosis), 627 (6.6%) participants were underweight at baseline and had at least two years of additional follow-up. 29 of 184 deaths were among underweight survivors. In univariate analysis, underweight status was more common among females (9.1% vs 4.5 %, p<0.01) and participants with younger age (8.2% for <5 yrs vs. 6.1% for >=5yr, p<.01), lower household income (8.9% for <$20,000 vs. 6.0% for >=$20,000, p<0.01), and a history of a grade 3 to 4 chronic condition (p = 0.05). After adjustment for these factors, in addition to race/ethnicity, prior smoking, and a history of radiation therapy, the odds of all-cause mortality within two years of BMI report was 2.82 (95% CI: 1.64-2.2; p<0.01) for underweight survivors, compared to normal weight survivors. The risk of subsequent malignant neoplasms within two years of BMI report among underweight survivors compared to normal weight survivors was not significantly increased (OR 1.31; 95% CI: 0.60-2.85; p = 0.49). Conclusions: Childhood cancer survivors who are underweight are at significant risk for late mortality that is unrelated to smoking status, chronic illness, or second malignancy. Whether targeted nutritional interventions would ameliorate this risk is unknown.

Long-Term Outcomes of Adjuvant Mitotane Therapy in Patients With Radically Resected Adrenocortical Carcinoma.

In 2007, a retrospective case-control study provided evidence that adjuvant mitotane prolongs recurrence-free survival (RFS) in patients with radically resected adrenocortical carcinoma (ACC). We aimed to confirm the prognostic role of adjuvant mitotane in the same series after 9 additional years of follow-up. One hundred sixty-two ACC patients who did not recur or die after a landmark period of 3 months were considered. Forty-seven patients were enrolled in four Italian centers where adjuvant mitotane was routinely recommended (mitotane group), 45 patients in four Italian centers where no adjuvant strategy was undertaken (control group 1), and 70 German patients left untreated after surgery (control group 2). The primary aim was RFS, the secondary was overall survival. An increased risk of recurrence was found in both control cohorts [group 1: hazard ratio (HR) = 2.98; 95% confidence interval (CI), 1.75 to 5.09; P < 0.0001; group 2: HR = 2.61; 95% CI, 1.56 to 4.36; P < 0.0001] compared with the mitotane group. The risk of death was higher in control group 1 (HR = 2.03; 95% CI, 1.17 to 3.51; P = 0.011) but not in control group 2 (HR = 1.60; 95% CI, 0.94 to 2.74; P = 0.083), which had better prognostic factors and more aggressive treatment of recurrences than control group 1. The benefit of adjuvant mitotane on RFS was observed regardless of the hormone secretory status. Adjuvant mitotane is associated with prolonged RFS, without any apparent influence by the tumor secretory status. The retrospective nature of the study is a major limitation.

Occupational Exposure to Pesticides and the Incidence of Lung Cancer in the Agricultural Health Study.

Background:Occupational pesticide use is associated with lung cancer in some, but not all, epidemiologic studies. In the Agricultural Health Study (AHS), we previously reported positive associations between several pesticides and lung cancer incidence.Objective:We evaluated use of 43 pesticides and 654 lung cancer cases after 10 years of additional follow-up in the AHS, a prospective cohort study comprising 57,310 pesticide applicators from Iowa and North Carolina.Methods:Information about lifetime pesticide use and other factors was ascertained at enrollment (1993–1997) and updated with a follow-up questionnaire (1999–2005). Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for smoking (smoking status and pack-years), sex, and lifetime days of use of any pesticides.Results:Hazard ratios were elevated in the highest exposure category of lifetime days of use for pendimethalin (1.50; 95% CI: 0.98, 2.31), dieldrin (1.93; 95% CI: 0.70, 5.30), and chlorimuron ethyl (1.74; 95% CI: 1.02, 2.96), although monotonic exposure–response gradients were not evident. The HRs for intensity-weighted lifetime days of use of these pesticides were similar. For parathion, the trend was statistically significant for intensity-weighted lifetime days (p = 0.049) and borderline for lifetime days (p = 0.073). None of the remaining pesticides evaluated was associated with lung cancer incidence.Conclusions:These analyses provide additional evidence for an association between pendimethalin, dieldrin, and parathion use and lung cancer risk. We found an association between chlorimuron ethyl, a herbicide introduced in 1986, and lung cancer that has not been previously reported. Continued follow-up is warranted.Citation:Bonner MR, Beane Freeman LE, Hoppin JA, Koutros S, Sandler DP, Lynch CF, Hines CJ, Thomas K, Blair A, Alavanja MCR. 2017. Occupational exposure to pesticides and the incidence of lung cancer in the Agricultural Health Study. Environ Health Perspect 125:544–551; http://dx.doi.org/10.1289/EHP456

An extremely indolent T-cell leukemia: an 18-year follow-up.

T-cell prolymphocytic leukemia (T-PLL) is a rare malignancy that comprises about 2% of all mature lymphoid neoplasms. Patients usually present with prominent peripheral blood lymphocytosis, splenomegaly, hepatomegaly, lymphadenopathy, B symptoms, and occasionally with skin lesions.¹ The disease follows an aggressive clinical course with rapid progression and typically has a median survival of less than 1 year. In some cases, the disease is indolent for a period of time before becoming aggressive.² In 2002, 7 years after initial diagnosis in 1995, the case discussed herein was reported as a rare, indolent form of T-PLL.³ We now present 11 additional years of follow-up of this case, during which time the patient remained asymptomatic with respect to his lymphoid neoplasm.

Brain Cancer in Workers Employed at a Laboratory Research Facility.

BackgroundAn earlier study of research facility workers found more brain cancer deaths than expected, but no workplace exposures were implicated.MethodsAdding four additional years of vital-status follow-up, we reassessed the risk of death from brain cancer in the same workforce, including 5,284 workers employed between 1963, when the facility opened, and 2007. We compared the work histories of the brain cancer decedents in relationship to when they died and their ages at death.ResultsAs in most other studies of laboratory and research workers, we found low rates of total mortality, total cancers, accidents, suicides, and chronic conditions such as heart disease and diabetes. We found no new brain cancer deaths in the four years of additional follow-up. Our best estimate of the brain cancer standardized mortality ratio (SMR) was 1.32 (95% confidence interval [95% CI] 0.66–2.37), but the SMR might have been as high as 1.69. Deaths from benign brain tumors and other non-malignant diseases of the nervous system were at or below expected levels.ConclusionWith the addition of four more years of follow-up and in the absence of any new brain cancers, the updated estimate of the risk of brain cancer death is smaller than in the original study. There was no consistent pattern among the work histories of decedents that indicated a common causative exposure.

Updated 6 Year Follow-Up Of The PRIMA Study Confirms The Benefit Of 2-Year Rituximab Maintenance In Follicular Lymphoma Patients Responding To Frontline Immunochemotherapy

Updated 6 Year Follow-Up Of The PRIMA Study Confirms The Benefit Of 2-Year Rituximab Maintenance In Follicular Lymphoma Patients Responding To Frontline Immunochemotherapy

Risk Of Solid Subsequent Malignant Neoplasms (SMNs) With Extended Follow-Up Of Childhood Hodgkin Lymphoma (HL) Survivors Is Comparable To The Risk In Known High-Risk Groups Within The General Population: Report From The Late Effects Study Group (LESG)

BackgroundWe describe the pattern and incidence of SMNs with 10 additional years of follow-up of an international cohort (Bhatia, N Engl J Med, 1996; Bhatia, J Clin Oncol, 2003) of children with HL diagnosed between 1955 and 1986 at age 16 y or younger. MethodsMedical record review was used to identify SMNs, define vital status and describe therapeutic exposures. Pathology reports served to validate SMNs. Cumulative incidence (CI) utilized competing risk methods. Standardized incidence ratio (SIR) and absolute excess risk (AER/10,000 p-y) utilized age-, gender- and year-matched rates in the general population. Cox regression techniques (using calendar time as time scale) identified predictors of SMN risk. ResultsThe cohort included 1023 patients diagnosed with HL at a median age of 11 y, and followed for a median of 26.8 y (IQR, 16.4-33.7). Eighty-nine percent had received radiation, either alone (22%), or in combination with chemotherapy (67%). Alkylating agent (AA) score was defined as follows: 1 AA for 6 m = AA score of 1; 2 AA for 6 m or 1 AA for 12 m = AA score of 2, etc. The AA score was 1-2 for 54% and 3+ for 16%; 30% did not receive AA. A total of 188 solid SMNs developed in 139 patients (breast [54], thyroid [24], lung [11], colorectal [11], bone [8], other malignancies [80]. Table summarizes SIR (95%CI), CI, and AER by attained age. The cohort was at an 11.1-fold increased risk of developing solid SMNs (excluding non-melanoma skin cancers) compared with the general population (95% CI, 9.4-13.0). CI of solid SMNs was 25.2% at 40 y from HL diagnosis (Fig 1). Among patients aged ≥40 y, 79% of total AER was attributable to breast, thyroid, colorectal and lung SMNs (Table). Thirty-seven patients developed >1 solid SMN; the cumulative incidence of the 2nd SMN was 19.6% at 10 years from diagnosis of the 1st SMN. Breast Cancer: Females (n=41) had a 20.9-fold increased risk, and males (n=3) a 45.8-fold increased risk c/w general population. Age at HL of 10-16 y vs. <10 y (RR=9.7, 95%CI, 2.3-40.6, p=0.002), and exposure to chest radiation (RR=5.9, 95%CI, 1.4-25.9) were associated with increased risk. Among females aged 10-16 y at chest radiation, cumulative incidence was 24.3% by age 45 y, as opposed to 2.6% for those <10 y, p=0.001 (Fig 2). Exposure to AA was associated with a lower risk (RR=0.4, p=0.002). Diagnosis of HL after 1975 was associated with decreased risk (RR=0.25, 95%CI 0.12-0.53), explained, in part by the increasing use of AA after 1975 (78%) vs. before 1975 (61%). By age 40 y, the risk of breast cancer among females exposed to chest radiation at age 10-16 y (18.2%) was comparable to the risk for BRCA1 mutation carriers (15%-20% by age 40 y; Chen, J Clin Oncol, 2007). Lung cancer: Ten of 11 lung cancer cases were diagnosed in males (males: SIR=24.7; females: SIR=3.2, p=0.05); all had received neck/chest radiation. The CI of lung cancer among males was 3.8% by age 50 y, comparable to the risk among male smokers (2% by age 50 y, Bilello, Clinics Chest Med, 2002). Colorectal cancer: There was a 11.5-fold increased risk c/w general population. The CI among those with abdominal/pelvic radiation was 4.1% by age 50 y ; this risk is higher than that observed in individuals with ≥2 first degree relatives affected with colorectal cancer (1.2% by age 50 y, Butterworth, Eur J Cancer, 2006). Thyroid cancer: Survivors had a 22.2-fold increased risk; all developed within radiation field. Females (RR=4.3, 95%CI 1.8-10.4) were at increased risk. ConclusionIn this cohort of HL survivors with 20,344 p-y of follow-up, the greatest excess risk of SMNs among those > 40 y was attributable to breast, thyroid, colorectal and lung SMNs. Observed risks for the most common SMNs were comparable to or greater than known high-risk groups within the general population. [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.Breast (n=44)Thyroid (n=24)Colorectal (n=11)Lung (n=11)Median age at diagnosis in yrs (range)37 (24-49)36 (17-53)36 (29-53)41 (22-46)Median latency from HL in yrs (range)25 ( 10-40)28 (8-45)25 (16-45)28 (12-34)SIR (95% CI)Overall21.7 (15.9-28.7)22.2 (14.4-32.2)11.5 (6.0-19.6)15.2 (7.9-26.1)Males45.8 (11.4-1118)31.4 (16.3-53.8)13.5 (6.2-25.1)24.7 (12.4-43.2)Females20.9 (15.1-27.9)17.7 (9.8-29.2)8.2 (2.0-21.2)3.2 (0.2-13.9)Cumulative Incidence in yrs form HL diagnosis20 y4.7% (F); 0% (M)1.0%0.3%0.2%30 y12.% (F); 0.2% (M)2.2%1.1%0.9%40 y20.5% (F); 1.1% (M)4.8%2.0%2.3%AER/ 10,000 p-y by attained age in y<20 y00.20020-39y2.51.20.50.4≥40 y7.43.62.02.5

Adjuvant treatment of premenopausal women with endocrine-responsive early breast cancer: Design of the TEXT and SOFT trials

ObjectivesIn 2003 the International Breast Cancer Study Group (IBCSG) initiated the TEXT and SOFT randomized phase III trials to answer two questions concerning adjuvant treatment for premenopausal women with endocrine-responsive early breast cancer: 1-What is the role of aromatase inhibitors (AI) for women treated with ovarian function suppression (OFS)? 2-What is the role of OFS for women who remain premenopausal and are treated with tamoxifen? MethodsTEXT randomized patients to receive exemestane or tamoxifen with OFS. SOFT randomized patients to receive exemestane with OFS, tamoxifen with OFS, or tamoxifen alone. Treatment was for 5 years from randomization. ResultsTEXT and SOFT successfully met their enrollment goals in 2011. The 5738 enrolled women had lower-risk disease and lower observed disease-free survival (DFS) event rates than anticipated. Consequently, 7 and 13 additional years of follow-up for TEXT and SOFT, respectively, were required to reach the targeted DFS events (median follow-up about 10.5 and 15 years). To provide timely answers, protocol amendments in 2011 specified analyses based on chronological time and median follow-up. To assess the AI question, exemestane + OFS versus tamoxifen + OFS, a combined analysis of TEXT and SOFT became the primary analysis (n = 4717). The OFS question became the primary analysis from SOFT, assessing the unique comparison of tamoxifen + OFS versus tamoxifen alone (n = 2045). The first reports are anticipated in mid- and late-2014. ConclusionsWe present the original designs of TEXT and SOFT and adaptations to ensure timely answers to two questions concerning optimal adjuvant endocrine treatment for premenopausal women with endocrine-responsive breast cancer.Trial RegistrationTEXT: Clinicaltrials.govNCT00066703SOFT: Clinicaltrials.govNCT00066690

Effects of Prior Intensive Versus Conventional Therapy and History of Glycemia on Cardiac Function in Type 1 Diabetes in the DCCT/EDIC

Intensive diabetes therapy reduces the prevalence of coronary calcification and progression of atherosclerosis and the risk of cardiovascular disease (CVD) events in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study. The effects of intensive therapy on measures of cardiac function and structure and their association with glycemia have not been explored in type 1 diabetes (T1DM). We assess whether intensive treatment compared with conventional treatment during the DCCT led to differences in these parameters during EDIC. After 6.5 years of intensive versus conventional therapy in the DCCT, and 15 years of additional follow-up in EDIC, left ventricular (LV) indices were measured by cardiac magnetic resonance (CMR) imaging in 1,017 of the 1,371 members of the DCCT cohort. There were no differences between the DCCT intensive versus conventional treatment in end diastolic volume (EDV), end systolic volume, stroke volume (SV), cardiac output (CO), LV mass, ejection fraction, LV mass/EDV, or aortic distensibility (AD). Mean DCCT/EDIC HbA1c over time was associated with EDV, SV, CO, LV mass, LV mass/EDV, and AD. These associations persisted after adjustment for CVD risk factors. Cardiac function and remodeling in T1DM assessed by CMR in the EDIC cohort was associated with prior glycemic exposure, but there was no effect of intensive versus conventional treatment during the DCCT on cardiac parameters.

Use of glucosamine and chondroitin supplements and risk of colorectal cancer

Glucosamine and chondroitin are non-vitamin, non-mineral supplements which have anti-inflammatory properties. These supplements are typically used for joint pain and osteoarthritis and are commonly taken as either glucosamine alone or glucosamine plus chondroitin. An exploratory analysis conducted within the VITamins And Lifestyle (VITAL) study observed any use of glucosamine and chondroitin to be associated with reduced risk of colorectal cancer (CRC) after 5 years of follow-up. With two additional years of follow-up, we have studied these associations in greater depth, including associations by frequency/duration of use and by formulation, and have evaluated whether observed associations are modified by factors associated with inflammation. Participants include 75,137 western Washington residents aged 50-76 who completed the mailed VITAL questionnaire between 2000 and 2002. Use of glucosamine and chondroitin was ascertained by questions about supplement use during the 10-year period prior to baseline, and participants were followed for CRC through 2008 (n = 557). Cox regression was used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs). Persons reporting use of glucosamine + chondroitin on 4+ days/week for 3+ years had a non-statistically significant 45 % lower CRC risk than non-users (HR: 0.55; 95 % CI 0.30-1.01; p-trend: 0.16). This association varied by body mass index (p-interaction: 0.006), with inverse association observed among the overweight/obese (p-trend: 0.02), but not among the underweight/normal weight. Use of glucosamine alone was not significantly associated with CRC risk. There is great need to identify safe and effective cancer preventive strategies, suggesting that glucosamine and chondroitin may merit further attention as a potential chemopreventive agent.

Periconceptional Folic Acid and Risk of Autism Spectrum Disorders

Periconceptional Folic Acid and Risk of Autism Spectrum Disorders

Studies of Mortality of Atomic Bomb Survivors. Report 13: Solid Cancer and Noncancer Disease Mortality: 1950–1997

This continues the series of general reports on mortality in the cohort of atomic bomb survivors followed up by the Radiation Effects Research Foundation. This cohort includes 86,572 people with individual dose estimates, 60% of whom have doses of at least 5 mSv. We consider mortality for solid cancer and for noncancer diseases with 7 additional years of follow-up. There have been 9,335 deaths from solid cancer and 31,881 deaths from noncancer diseases during the 47-year follow-up. Of these, 19% of the solid cancer and 15% of the noncancer deaths occurred during the latest 7 years. We estimate that about 440 (5%) of the solid cancer deaths and 250 (0.8%) of the noncancer deaths were associated with the radiation exposure. The excess solid cancer risks appear to be linear in dose even for doses in the 0 to 150-mSv range. While excess rates for radiation-related cancers increase throughout the study period, a new finding is that relative risks decline with increasing attained age, as well as being highest for those exposed as children as noted previously. A useful representative value is that for those exposed at age 30 the solid cancer risk is elevated by 47% per sievert at age 70. There is no significant city difference in either the relative or absolute excess solid cancer risk. Site-specific analyses highlight the difficulties, and need for caution, in distinguishing between site-specific relative risks. These analyses also provide insight into the difficulties in interpretation and generalization of LSS estimates of age-at-exposure effects. The evidence for radiation effects on noncancer mortality remains strong, with risks elevated by about 14% per sievert during the last 30 years of follow-up. Statistically significant increases are seen for heart disease, stroke, digestive diseases, and respiratory diseases. The noncancer data are consistent with some non-linearity in the dose response owing to the substantial uncertainties in the data. There is no direct evidence of radiation effects for doses less than about 0.5 Sv. While there are no statistically significant variations in noncancer relative risks with age, age at exposure, or sex, the estimated effects are comparable to those seen for cancer. Lifetime risk summaries are used to examine uncertainties of the LSS noncancer disease findings.

Ischemic Heart Disease in Nuclear Workers First Employed at the Mayak PA in 1948–1972

Following an earlier study of incidence and mortality of ischemic heart disease (IHD) published in 2010, a second analysis has been conducted based on an extended cohort and five additional years of follow-up. The cohort includes 18,763 workers, of whom 25% were females, first employed at the Mayak PA in 1948-1972 and followed up to the end of 2005. Some of these workers were exposed to external gamma rays only, and others were exposed to a mixture of external gamma-rays and internal alpha-particle radiation. A total of 6,134 cases and 2,629 deaths from IHD were identified in the study cohort. A statistically significant increasing trend was found with total external gamma-ray dose in IHD incidence (ERR/Gy 0.099; 95% CI: 0.045-0.153) after adjusting for non-radiation factors. This value reduced slightly when adjusting for internal liver dose. There was no statistically significant increase trend for internal liver dose in IHD incidence. These findings were consistent with an earlier study. New findings in IHD incidence revealed a statistically significant decrease in IHD incidence among workers exposed to external gamma-rays doses of 0.2-0.5 Gy in relation to the external doses below 0.2 Gy. This decreased risk is heavily influenced by female workers. This finding has never been reported in other studies, and the results should be treated with caution. The findings for IHD mortality are similar to those results in the earlier analysis; there was no statistically significant trend with external gamma-ray dose or for internal liver dose after adjustment for external dose. The risk estimates obtained from these analyses of IHD incidence and mortality in relation to external gamma-rays in the cohort of Mayak workers are generally compatible with those from other large occupational radiation worker studies and the Japanese atomic bomb survivors.

Chronic Exposure to Fine Particles and Mortality: An Extended Follow-up of the Harvard Six Cities Study from 1974 to 2009

Background: Epidemiologic studies have reported associations between fine particles (aerodynamic diameter ≤ 2.5 µm; PM2.5) and mortality. However, concerns have been raised regarding the sensitivity of the results to model specifications, lower exposures, and averaging time.Objective: We addressed these issues using 11 additional years of follow-up of the Harvard Six Cities study, incorporating recent lower exposures.Methods: We replicated the previously applied Cox regression, and examined different time lags, the shape of the concentration–response relationship using penalized splines, and changes in the slope of the relation over time. We then conducted Poisson survival analysis with time-varying effects for smoking, sex, and education.Results: Since 2001, average PM2.5 levels, for all six cities, were < 18 µg/m3. Each increase in PM2.5 (10 µg/m3) was associated with an adjusted increased risk of all-cause mortality (PM2.5 average on previous year) of 14% [95% confidence interval (CI): 7, 22], and with 26% (95% CI: 14, 40) and 37% (95% CI: 7, 75) increases in cardiovascular and lung-cancer mortality (PM2.5 average of three previous years), respectively. The concentration–response relationship was linear down to PM2.5 concentrations of 8 µg/m3. Mortality rate ratios for PM2.5 fluctuated over time, but without clear trends despite a substantial drop in the sulfate fraction. Poisson models produced similar results.Conclusions: These results suggest that further public policy efforts that reduce fine particulate matter air pollution are likely to have continuing public health benefits.

Prostate-Cancer Mortality at 11 Years of Follow-up

BackgroundSeveral trials evaluating the effect of prostate-specific antigen (PSA) testing on prostate-cancer mortality have shown conflicting results. We updated prostate-cancer mortality in the European Randomized Study of Screening for Prostate Cancer with 2 additional years of follow-up.MethodsThe study involved 182,160 men between the ages of 50 and 74 years at entry, with a predefined core age group of 162,388 men 55 to 69 years of age. The trial was conducted in eight European countries. Men who were randomly assigned to the screening group were offered PSA-based screening, whereas those in the control group were not offered such screening. The primary outcome was mortality from prostate cancer.ResultsAfter a median follow-up of 11 years in the core age group, the relative reduction in the risk of death from prostate cancer in the screening group was 21% (rate ratio, 0.79; 95% confidence interval [CI], 0.68 to 0.91; P=0.001), and 29% after adjustment for noncompliance. The absolute reduction in mortality in the screening group was 0.10 deaths per 1000 person-years or 1.07 deaths per 1000 men who underwent randomization. The rate ratio for death from prostate cancer during follow-up years 10 and 11 was 0.62 (95% CI, 0.45 to 0.85; P=0.003). To prevent one death from prostate cancer at 11 years of follow-up, 1055 men would need to be invited for screening and 37 cancers would need to be detected. There was no significant between-group difference in all-cause mortality.ConclusionsAnalyses after 2 additional years of follow-up consolidated our previous finding that PSA-based screening significantly reduced mortality from prostate cancer but did not affect all-cause mortality. (Current Controlled Trials number, ISRCTN49127736.)

Body Mass Index, Playing Position, Race, and the Cardiovascular Mortality of Retired Professional Football Players

Concern exists about cardiovascular disease (CVD) in professional football players. We examined whether playing position and size influence CVD mortality in 3,439 National Football League players with ≥ 5 pension-credited playing seasons from 1959 to 1988. Standardized mortality ratios (SMRs) compared player mortality through 2007 to the United States population of men stratified by age, race, and calendar year. Cox proportional hazards models evaluated associations of playing-time body mass index (BMI), race, and position with CVD mortality. Overall player mortality was significantly decreased (SMR 0.53, 95% confidence interval [CI] 0.48 to 0.59) as was mortality from cancer (SMR 0.58, 95% CI 0.46 to 0.72), and CVD (SMR 0.68, 95% CI 0.56 to 0.81). CVD mortality was increased for defensive linemen (SMR 1.42, 95% CI 1.02 to 1.92) but not for offensive linemen (SMR 0.70, 95% CI 0.45 to 1.05). Defensive linemen's cardiomyopathy mortality was also increased (SMR 5.34, 95% CI 2.30 to 10.5). Internal analyses found that CVD mortality was increased for players of nonwhite race (hazard ratio 1.69, 95% CI 1.13 to 2.51). After adjusting for age, race, and calendar year, CVD mortality was increased for those with a playing-time BMI ≥ 30 kg/m2 (hazard ratio 2.02, 95% CI 1.06 to 3.85) and for defensive linemen compared to offensive linemen (hazard ratio 2.07, 95% CI 1.24 to 3.46). In conclusion, National Football League players from the 1959 through 1988 seasons had decreased overall mortality but those with a playing-time BMI ≥ 30 kg/m2 had 2 times the risk of CVD mortality compared to other players and African-American players and defensive linemen had higher CVD mortality compared to other players even after adjusting for playing-time BMI.

Studies of the Mortality of Atomic Bomb Survivors, Report 14, 1950–2003: An Overview of Cancer and Noncancer Diseases

This is the 14th report in a series of periodic general reports on mortality in the Life Span Study (LSS) cohort of atomic bomb survivors followed by the Radiation Effects Research Foundation to investigate the late health effects of the radiation from the atomic bombs. During the period 1950-2003, 58% of the 86,611 LSS cohort members with DS02 dose estimates have died. The 6 years of additional follow-up since the previous report provide substantially more information at longer periods after radiation exposure (17% more cancer deaths), especially among those under age 10 at exposure (58% more deaths). Poisson regression methods were used to investigate the magnitude of the radiation-associated risks, the shape of the dose response, and effect modification by gender, age at exposure, and attained age. The risk of all causes of death was positively associated with radiation dose. Importantly, for solid cancers the additive radiation risk (i.e., excess cancer cases per 10(4) person-years per Gy) continues to increase throughout life with a linear dose-response relationship. The sex-averaged excess relative risk per Gy was 0.42 [95% confidence interval (CI): 0.32, 0.53] for all solid cancer at age 70 years after exposure at age 30 based on a linear model. The risk increased by about 29% per decade decrease in age at exposure (95% CI: 17%, 41%). The estimated lowest dose range with a significant ERR for all solid cancer was 0 to 0.20 Gy, and a formal dose-threshold analysis indicated no threshold; i.e., zero dose was the best estimate of the threshold. The risk of cancer mortality increased significantly for most major sites, including stomach, lung, liver, colon, breast, gallbladder, esophagus, bladder and ovary, whereas rectum, pancreas, uterus, prostate and kidney parenchyma did not have significantly increased risks. An increased risk of non-neoplastic diseases including the circulatory, respiratory and digestive systems was observed, but whether these are causal relationships requires further investigation. There was no evidence of a radiation effect for infectious or external causes of death.

Prostate-specific antigen testing in Tyrol, Austria: prostate cancer mortality reduction was supported by an update with mortality data up to 2008

Prostate-specific antigen testing in Tyrol, Austria: prostate cancer mortality reduction was supported by an update with mortality data up to 2008

Abstract A63: Genetic and environmental factors in cancer incidence: An updated analysis from the Nordic Twin Registry of Cancer

Abstract Background: Quantifying the relative contributions of genetic and environmental factors in cancer incidence informs etiology and opportunities for prevention. Studies based on large twin cohorts afford a unique opportunity to directly estimate the relative contribution of these factors. We are updating an analysis within the Nordic Twin Registry of Cancer (NorTwinCan), with the expansion of the original cohort, addition of a national twin registry for Norway, and on average 10 additional years of follow-up for cancer incidence. Methods: NorTwinCan includes 105,306 monozygotic (MZ) and dizygotic (DZ) twin pairs (N=210,612 total) from population-based registries in Denmark, Finland, Norway and Sweden. The twins were followed prospectively for cancer incidence and mortality by linkage with national cancer registries through 2008, with up to six decades of follow-up. We calculated zygosity- and sex-specific proband concordance rates for 20 unique cancer sites, and estimated the relative risk (RR) of a cancer in an individual given his/her co-twin had cancer compared to individuals where the co-twin did not have cancer. Results: During follow-up, 29,599 cancers were diagnosed. The co-twin of a twin with cancer had an increased risk of having the same cancer for most malignancies. For prostate cancer, the proband concordance rates were 0.298 among MZ twins and 0.138 among DZ twins. These estimates translate to a 29.8 percent probability that the MZ genetically identical twin of a man with prostate cancer will also be diagnosed with prostate cancer, and a 13.8 percent probability for DZ twins who are genetically alike as siblings. For MZ twins, the relative risk of prostate cancer was 19.8 if the co-twin had cancer, four-fold greater than the relative risk estimate for DZ pairs. For breast cancer among women, proband concordance rates were 0.173 for MZ and 0.110 for DZ twins. The relative risk of breast cancer if the co-twin had breast cancer was higher in MZ (RR=7.3) than DZ (RR=3.3) twins. The relative risk estimates were similarly higher in MZ compared to DZ twin pairs for cancers of the lung (e.g. RRMZ=23.5 versus RRDZ=8.2 for women), stomach (RRMZ=24.8 versus RRDZ=9.1 for women), testes (RRMZ=33.8 versus RRDZ=16.0), bladder (RRMZ=11.3 versus RRDZ=4.2 for men), corpus uteri (RRMZ=10.1 versus RRDZ=3.1), and ovary (RRMZ=10.3 versus RRDZ=2.6). Quantitative genetic modeling to estimate heritability of each cancer site is ongoing, and will account for censoring and competing causes of death. Discussion: These preliminary analyses indicate a strong genetic component in the etiology of most malignancies, based on the greater relative risk and concordances in MZ versus DZ twin pairs. NorTwinCan is the largest twin study of cancer, and quantitative genetic modeling will quantify the relative contributions of genetic and environmental factors to variation in cancer incidence with greater precision than previously estimated, including for the more rare cancers. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A63.

Atrazine and cancer incidence among pesticide applicators in the Agricultural Health Study (1994–2007)

ObjectivesAtrazine is a triazine herbicide with endocrine-disrupting properties and is used widely in the United States. Atrazine causes mammary tumours in rats, but the mechanism does not appear to operate...