Approaches to the diagnosis and management of hepatocellular carcinoma (HCC) are improving survival. In the Surveillance, Epidemiology and End Results-13 registries, HCC stage, histological confirmation and first course surgery were examined. Among 21,390 HCC cases diagnosed during examined during 1998-2008 there were 4,727 (22%) with reported first course invasive liver surgery, local tumor destruction, or both. The proportion with reported liver surgery or ablation was 39% among localized stage cases and only 4% among distant/unstaged cases. While 70% of cases had histologically confirmed diagnoses, the proportion with confirmed diagnoses was higher among cases with reported invasive surgery (99%) compared to cases receiving ablation (81%) or no reported therapy (65%). Incidence rates of histologically unconfirmed HCC increased faster than those of confirmed HCC from 1992 to 2008 (8% versus 3% per year). Two encouraging findings were that incidence rates of localized stage HCC increased faster than rates of regional and distant stage HCC combined (8% versus 4% per year) and that incidence rates of reported first course surgery or tumor destruction increased faster than incidence rates of HCC without such therapy (11% versus 7%). Between 1975-1977 and 1998-2007, 5-year cause-specific HCC survival increased from just 3% to 18%. Survival was 84% among transplant recipients, 53% among cases receiving radiofrequency ablation at early stage, 47% among cases undergoing resection, and 35% among cases receiving local tumor destruction. Asian or Pacific Islander cases had significantly better 5-year survival (23%) than white (18%), Hispanic (15%), or black cases (12%).
HCC survival is improving as more cases are diagnosed and treated at early stages. Additional progress may be possible with continued use of clinical surveillance to follow individuals at risk for HCC, enabling early intervention.
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce chronic inflammation and risk of many cancers, but their effect on risk of hepatocellular carcinoma (HCC) and death due to chronic liver disease (CLD) has not been investigated.
We analyzed prospective data on 300504 men and women aged 50 to 71 years in the National Institutes of Health–AARP Diet and Health Study cohort and linked self-reported aspirin and nonaspirin NSAID use with registry-confirmed diagnoses of HCC (n=250) and death due to CLD (n=428, excluding HCC). We calculated hazard rate ratios (RRs) and their two-sided 95% confidence intervals (CIs) using Cox proportional hazard regression models with adjustment for age, sex, race/ethnicity, cigarette smoking, alcohol consumption, diabetes, and body mass index. All tests of statistical significance were two-sided.
Aspirin users had statistically significant reduced risks of incidence of HCC (RR = 0.59; 95% CI = 0.45 to 0.77) and mortality due to CLD (RR = 0.55; 95% CI = 0.45 to 0.67) compared to those who did not use aspirin. In contrast, users of nonaspirin NSAIDs had a reduced risk of mortality due to CLD (RR = 0.74; 95% CI= 0.61 to 0.90) but did not have lower risk of incidence of HCC (RR = 1.08; 95% CI = 0.84 to 1.39) compared to those who did not use nonaspirin NSAIDs. The risk estimates did not vary in statistical significance by frequency (monthly, weekly, daily) of aspirin use, but the reduced risk of mortality due to CLD was statistically significant only among monthly users of nonaspirin NSAIDs compared to non-users.
Aspirin use was associated with reduced risk of developing HCC and of death due to CLD whereas nonaspirin NSAID use was only associated with reduced risk of death due to CLD.
We conducted a meta-analysis to identify new loci for testicular germ cell tumor (TGCT) susceptibility. In the discovery phase, 931 affected individuals and 1,975 controls from three genome wide association studies (GWAS) were analyzed. Replication was conducted in six independent sample sets totaling 3,211 affected individuals and 7,591 controls. In the combined analysis, TGCT risk was significantly associated with markers at four novel loci: 4q22.2 in HPGDS (per allele odds ratio (OR) 1.19, 95%CI 1.12–1.26, P = 1.11×10−8); 7p22.3 in MAD1L1 (OR 1.21, 95%CI 1.14–1.29, P = 5.59×10−9); 16q22.3 in RFWD3 (OR 1.26, 95%CI 1.18–1.34, P = 5.15×10−12); and 17q22 (rs9905704; OR 1.27, 95%CI 1.18–1.33; P = 4.32×10−13, and rs7221274; OR 1.20, 95%CI 1.12–1.28 P = 4.04×10−9), a locus which includes TEX14, RAD51C and PPM1E. The new TGCT susceptibility loci contain biologically plausible genes encoding proteins important for male germ cell development, chromosomal segregation and DNA damage response.
To evaluate the association of body size – captured via whole body dual-energy x-ray absorptiometry (DXA) and physical measurement – with serum sex steroid hormones and sex hormone binding globulin (SHBG) we utilized cross-sectional data and serum samples from the National Health and Nutrition Examination Survey (NHANES; 1999-2004).
Testosterone, androstanediol glucuronide (3-alpha-diol-G), estradiol and SHBG were measured via immunoassay in serum samples from a total of 898 adult men (ages 20-90) participating in the morning examination. As part of the NHANES data collection DXA scans and measurements of weight, height and waist circumference were performed by trained staff. Linear regression was used to estimate associations between body size and hormone levels adjusted for potential confounders and NHANES sampling procedures.
Total bone area (cm2) was inversely associated with total testosterone (ng/mL) [beta=-0.12; p-value<0.01], while bone mineral density (g/cm2) was inversely associated with SHBG (nmol/L) [beta=-17.16; p-value=0.01]. Increased percent body fat was associated with lower concentrations of total testosterone [beta=-0.16; p-value<0.01] and SHBG [beta=-1.11; p-value<0.01] and higher concentrations of free estradiol (fg/mL) [beta=12.52; p-value<0.01].
Clinical measures of body fat (measured via DXA scan) and anthropometric measures of body fat (BMI and waist circumference) provided similar inferences regarding the association between increased body fat and hormone levels in men. Increased body fat was associated with lower circulating levels of testosterone (total and free) and SHBG and higher circulating levels of free estradiol in men, while decreased bone mineral density was associated with higher circulating levels of SHBG.
dual-energy X-ray absorptiometry; DXA; estradiol; testosterone; androstanediol glucuronide; sex hormone binding globulin; National Health and Nutrition Examination Survey; NHANES; men
Surveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is recommended but may not be performed. The extent and determinants of HCC surveillance are unknown.
We conducted a population-based US cohort study of those over 65 years of age to examine utilization and determinants of pre-diagnosis surveillance in patients with HCC who were previously diagnosed with cirrhosis. Patients diagnosed with HCC during 1994-2002 were identified from the linked Surveillance, Epidemiology, and End-Results registry-Medicare databases. We identified alpha-fetoprotein and ultrasound tests performed for HCC surveillance, and examined factors associated with surveillance.
We identified 1,873 HCC patients with a prior diagnosis of cirrhosis. In the 3 years before HCC, 17% received regular surveillance and 38% received inconsistent surveillance. In a subset of 541 patients in whom cirrhosis was recorded for 3 or more years prior to HCC, only 29% received routine surveillance and 33% inconsistent surveillance. Among all patients who received regular surveillance, approximately 52% received both alpha-fetoprotein and ultrasound, 46% received alpha-fetoprotein only, and 2% received ultrasound only. Patients receiving regular surveillance were more likely to have lived in urban areas and had higher incomes than those who did not receive surveillance. Before diagnosis, approximately 48% of patients were seen by a gastroenterologist/hepatologist or by a physician with an academic affiliation; they were approximately 4.5-fold and 2.8-fold, respectively, more likely to receive regular surveillance than those seen by a primary care physician only. Geographic variation in surveillance was observed and explained by patient and physician factors.
Less than 20% of patients with cirrhosis who developed HCC received regular surveillance. Gastroenterologists/hepatologists or physicians with an academic affiliation are more likely to perform surveillance.
Hepatocellular carcinoma; cirrhosis; AFP; ultrasound; surveillance
We conducted a population-based study to describe the utilization, determinants, and survival effects of adjuvant therapies following surgery among older patients with pancreatic cancer.
Using SEER-Medicare data, we identified patients >65 years who received surgical resection for pancreatic cancer during 1992–2002. We constructed multiple logistic regression models to examine patient, clinical, and hospital factors associated with receiving adjuvant therapy. Cox proportional hazards models were used to examine the effect of therapy on survival.
Approximately 49% of patients received adjuvant therapy following surgery. Patient factors associated with increased receipt of adjuvant therapy included more recent diagnosis, younger age, stage II disease, higher income, and geographic location. Hospital factors associated with increased receipt of adjuvant therapy included cooperative group membership and larger size. Adjuvant treatments associated with a significant reduction in 2-year mortality (relative to surgery alone) were chemoradiation or radiation alone, but not chemotherapy alone.
Our findings suggest that adjuvant chemoradiation and to a lesser degree radiation only, are associated with a reduction in the risk of mortality among older patients who undergo surgery for pancreatic cancer. However, receipt of adjuvant therapy varied by time period and geography as well as certain patient and hospital factors.
Pancreatic cancer; adjuvant therapy; SEER-Medicare
To evaluate the utilization and determinants of receiving palliative treatment for HCC, and its effect on survival.
Palliative treatment for hepatocellular carcinoma (HCC), including transarterial chemoembolization (TACE) and systemic chemotherapy, is available for patients who do not receive potentially curative therapy. The utilization and outcomes of these therapies in clinical practice are unknown.
We conducted a population-based cohort study using Surveillance, Epidemiology, and End-Results registry data linked to Medicare claims of HCC patients >65 years diagnosed during 2000–2005 who did not receive liver transplant, resection, or ablation. The proportions of patients who received TACE or systemic chemotherapy were calculated by tumor stage, liver disease status, and non-HCC co-morbidity. Determinants of receiving palliative therapy were examined in logistic regression models and propensity scores were calculated. Cox proportional hazards models were used to evaluate mortality risk.
We identified 3,163 HCC patients (median age: 75 yrs, 67% men) who did not receive potentially curative treatment. Approximately 12.5% received TACE and 11.0% chemotherapy. In patients with early or intermediate stage HCC, no liver decompensation, and little or no co-morbidity, only 22.8% received TACE and 13.8% chemotherapy. Median survival was significantly higher among patients who received TACE (14.0 months) compared to chemotherapy (5.0 months) or no therapy (2.0 months). A significant reduction in overall mortality was observed for TACE (54%) and chemotherapy (33%).
Utilization of palliative treatment for HCC is low, which could not be explained by clinical features. However, misclassification could have occurred due to the data source. Receipt of TACE or systemic chemotherapy was associated with a reduction in mortality.
Hepatocellular carcinoma; palliative treatment; chemotherapy
Excess alcohol consumption adversely affects one-carbon metabolism and increases the risk of liver disease and liver cancer. Conversely, higher folate levels have been inversely associated with liver damage. The current study investigated the effects of alcohol and one-carbon metabolite intake on liver cancer incidence and liver disease mortality within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study.
Cox proportional hazards modeling was used to calculate hazard ratios and 95% confidence intervals (CIs) in a population of 27,086 Finnish males with 194 incident liver cancers and 213 liver disease deaths. In a nested case-control subset (95 liver cancers, 103 controls), logistic regression was used to calculate odds ratios and 95% CIs for serum one-carbon metabolites in relation to liver cancer risk.
Daily alcohol consumption of more than 20.44 g was associated with an increased risk of both liver cancer incidence (Hazard Ratio (HR) 1.52, 95%CI 1.06–2.18) and liver disease mortality (HR 6.68, 95%CI 4.16–10.71). These risks were unaffected by one-carbon metabolite intake. Similarly, in the case-control study, none of the serum one-carbon metabolites were associated with liver cancer.
The current study provided no convincing evidence for a protective association of one-carbon metabolite intake or serum level on the risk of liver cancer or liver disease mortality.
The current working model of type II testicular germ cell tumor (TGCT) pathogenesis states that carcinoma in situ (CIS): arises during embryogenesis; is a necessary precursor; and always progresses to cancer. An implicit condition of this model is that only in utero exposures affect development of TGCT in later life. In an age-period-cohort analysis, this working model contends an absence of calendar period deviations. We tested this contention using data from the SEER registries of the United States.
We assessed age-period-cohort models of TGCTs, seminomas, and nonseminomas for the period 1973–2008. Analyses were restricted to whites diagnosed at ages 15 to 74 years. We tested whether calendar period deviations were significant in TGCT incidence trends adjusted for age deviations and cohort effects.
This analysis included 32,250 TGCTs (18,475 seminomas, 13,775 nonseminomas). Seminoma incidence trends have increased with an average annual percentage change in log-linear rates (net drift) of 1.25%, relative to just 0.14% for nonseminoma. In more recent time periods, TGCT incidence trends have plateaued and then undergone a slight decrease. Calendar period deviations were highly statistically significant in models of TGCT (p=1.24−9) and seminoma (p=3.99−14), after adjustment for age deviations and cohort effects; results for nonseminoma (p=0.02) indicated that the effects of calendar period were much more muted.
Calendar period deviations play a significant role in incidence trends of TGCT which indicates that postnatal exposures are etiologically relevant.
testicular cancer; age-period-cohort; carcinoma in-situ; calendar period deviations
Beta-adrenergic signaling is involved in many processes that may contribute to cancer progression. In this issue of the journal (beginning on page XX), Nkontchou and colleagues report their retrospective observational finding that the beta-blocker propranolol was associated with a highly statistically significant reduction in the incidence of hepatocellular carcinoma in patients with advanced cirrhosis and related esophageal varices. This surprising finding requires confirmation, but the result is biologically plausible. Epidemiologic studies have linked beta-blockade with reduced rates of metastasis of other cancers and reduced cancer mortality. Laboratory studies suggest biological mechanisms for anti-cancer effects of beta-blockers.
Hepatocellular carcinoma (HCC) has a poor prognosis and, unlike most cancers, HCC incidence and mortality rates are increasing in the United States. While risk is known to vary among different racial and ethnic groups, less is known about the variability of risk within these groups by neighborhood socioeconomic status (SES).
HCC cases diagnosed in the Surveillance, Epidemiology and End Results (SEER) 11 cancer registries between 1996 and 2007, and the population of the SEER 11 catchment areas was studied. Analyses were conducted to compare census tract area family poverty, educational attainment, and unemployment by race and ethnicity. A multiple linear regression model, weighted by the number of cases and the number of individuals in each census tract, with adjustment for registry, was used to calculate mean differences in area-level attributes between HCC cases and the population.
HCC cases in most racial/ethnic groups had lower mean neighborhood-level measures of SES than their referent population. An exception was seen among Hispanics. Comparing white cases with cases of other racial groups and to Hispanics, white cases lived in neighborhoods with less family poverty, fewer high-school dropouts, and lower unemployment. Compared with white cases, Asian and Pacific Islander and Hispanic cases lived in neighborhoods with a higher percentage of foreign-born population.
Low neighborhood-level SES and immigrant status may be associated with greater risk of HCC within specific racial and ethnic groups.
These findings could help to focus control resources for HCC toward the most affected communities.
Sexual function among testicular cancer survivors is a concern because affected men are of reproductive age when diagnosed. We conducted a case-control study among United States military men to examine whether testicular cancer survivors experienced impaired sexual function.
A total of 246 testicular cancer cases and 236 ethnicity and age matched controls were enrolled in the study in 2008-2009. The Brief Male Sexual Function Inventory (BMSFI) was used to assess sexual function.
Compared to controls, cases scored significantly lower on sex drive (5.77 vs. 5.18), erection (9.40 vs. 8.63), ejaculation (10.83 vs. 9.90), and problem assessment (10.55 vs. 9.54). Cases were significantly more likely to have impaired erection (OR 1.72; 95% CI 1.11-2.64), ejaculation (OR 2.27; 95% CI 1.32-3.91), and problem assessment (OR 2.36; 95% CI 1.43-3.90). In histology and treatment analysis, nonseminoma, chemotherapy and radiation treated cases risk of erectile dysfunction, delayed ejaculation, and/or problem assessment were greater when compared to controls.
This study provides evidence that testicular cancer survivors are more likely to have impaired sexual functioning compared to demographically matched controls. The observed impaired sexual functioning appeared to vary by treatment regimen and histologic subtype.
Testicular cancer; sexual function; military men
Despite a potential preventive effect of physical activity on hepatobiliary cancer, little information is available on the relation between the two. We studied the association between frequency of vigorous physical activity and hepatobiliary cancer among 507,897 participants of the NIH-AARP Diet and Health Study, aged 50 to 71 years at baseline in 1995/1996. During ten years of follow-up, 628 incident cases of liver cancer and 317 cases of extrahepatic biliary tract cancer were registered. Physical activity levels were assigned according to the frequency of engagement in 20 minutes or more of vigorous physical activity per week: never/rarely (lowest level), less than once per week, 1 to 2 times per week, 3 to 4 times per week, 5 or more times per week (highest level). Using Cox regression, multivariate-adjusted relative risks (RR) comparing the highest with the lowest level of physical activity revealed a statistically significant decreased risk for liver cancer (RR=0.64, 95% confidence interval (CI)=0.49–0.84, p-trend<0.001), particularly hepatocellular carcinoma (RR=0.56, 95% CI=0.41–0.78, p-trend<0.001), independent of body mass index. By comparison, multivariate analyses indicated that physical activity was not statistically significantly associated with extrahepatic bile duct cancer (RR=0.86, 95% CI=0.45–1.65), ampulla of Vater cancer (RR=0.66, 95% CI=0.29–1.48), or gallbladder cancer (RR=0.63, 95% CI=0.33–1.21). These results suggest a potential preventive effect of physical activity on liver cancer but not extrahepatic biliary tract cancer, independent of body mass index.
Physical activity; liver cancer; biliary cancer; gallbladder cancer; cohort study
It has been hypothesized that the risk of testicular germ cell tumors (TGCT) is associated with maternal hormone levels. To examine the hypothesis, some studies have used perinatal factors as surrogates for hormone levels. To determine the validity of this assumption, hormone-perinatal factor relationships were examined in the Collaborative Perinatal Project.
Maternal estradiol, estriol and testosterone levels in first and third trimester serum samples were correlated with perinatal factors among 300 mothers representative of populations at high (white Americans) or low (black Americans) risk of TGCT.
Among white participants, testosterone levels, were negatively associated with maternal height (p<0.01) and age (p=0.02), and positively associated with maternal weight (p=0.02) and BMI (p<0.01), while estradiol levels were negatively associated with height (p=0.03) and positively associated with son’s birthweight (p=0.04). Among black participants, estriol levels were negatively associated with maternal weight (p=0.01), BMI (p=0.02) and gestational age p<0.01), and positively associated with son’s birthweight (p<0.01), length (p=0.04) and head circumference (p=0.03).
These findings indicate that the use of perinatal characteristics as surrogates for hormone levels should be limited to a specific ethnic group. Among white men, previously reported associations of TGCT with maternal weight and age may be due to lower maternal testosterone levels.
testicular cancer; maternal hormones; perinatal factors
Androgen levels during critical periods of testicular development may be involved in the etiology of testicular germ cell tumors (TGCT). We evaluated the roles of adolescent and early adult life correlates of androgen exposure and TGCT in a hospital-based case control study. TGCT cases (n=187) and controls (n=148), matched on age, race and state of residence, participated in the study. Unconditional logistic regression was used to estimate associations between TGCT and male pattern baldness, severe acne, markers of puberty onset and body size. Cases were significantly less likely to report hair loss than controls (OR, 0.6; 95% CI, 0.4, 1.0). Amount of hair loss, increasing age at onset and increasing rate of loss were all inversely associated with TGCT (rate of hair loss: p-trend=0.03; age at onset: p-trend=0.03; amount of hair loss: p-trend=0.01). History of severe acne was inversely associated with TGCT (OR, 0.5; 95% CI, 0.3, 0.9) and height was positively associated with TGCT (p-trend=0.02). Increased endogenous androgen levels during puberty and early adulthood may be associated with decreased risk of TGCT. Additional studies of endogenous hormone levels during puberty and early adult life are warranted, especially studies evaluating the role of androgen synthesis, metabolism and uptake.
Testicular germ cell tumors; baldness; acne; hospital-based; case-control
Fumonisin B1 (FB1), a mycotoxin that contaminates corn in certain climates, has been demonstrated to cause hepatocellular cancer (HCC) in animal models. Whether a relationship between FB1 and HCC exists in humans is not known. To examine the hypothesis, we conducted case-control studies nested within two large cohorts in China; the Haimen City Cohort and the General Population Study of the Nutritional Intervention Trials cohort in Linxian. In the Haimen City Cohort, nail FB1 levels were determined in 271 HCC cases and 280 controls. In the General Population Nutritional Intervention Trial, nail FB1 levels were determined in 72 HCC cases and 147 controls. In each population, odds ratios and 95% confidence intervals (95%CI) from logistic regression models estimated the association between measurable FB1 and HCC, adjusting for hepatitis B virus infection and other factors. A meta-analysis that included both populations was also conducted. The analysis revealed no statistically significant association between FB1 and HCC in either Haimen City (OR=1.10, 95%CI=0.64–1.89) or in Linxian (OR=1.47, 95%CI=0.70–3.07). Similarly, the pooled meta-analysis showed no statistically significant association between FB1 exposure and HCC (OR=1.22, 95%CI=0.79–1.89). These findings, although somewhat preliminary, do not support an associated between FB1 and HCC.
fumonisin; hepatocellular carcinoma; cohort study; China; epidemiology
Tumor stage at diagnosis often varies by racial/ethnic group, possibly due to inequitable healthcare access. Within the Department of Defense (DoD) Military Health System, beneficiaries have equal healthcare access. This study aimed to determine if tumor stage differed between whites and blacks for breast, cervical, colorectal and prostate cancers, which have effective screening regimens, based on data from the DoD’s Automated Cancer Tumor Registry from 1990–2003.
Distributions of tumor stage (localized vs. non-localized) between whites and blacks in the military were compared stratified by sex, active duty status, and age at diagnosis. Logistic regression was used to further adjust for age, marital status, year of diagnosis, geographic region, military service branch and tumor grade. Distributions of tumor stage were then compared between the military and general populations.
Racial differences in the distribution of stage were significant only among non-active duty beneficiaries. After adjusting for covariates, earlier stages of breast cancer after age 49 and prostate cancer after age 64 were significantly more common among white than black non-active duty beneficiaries (p<0.05), although the absolute difference for prostate cancer was minimal. Racial differences in stage for cervical and colorectal cancers were not significant after adjustment. Compared to the general population, the racial differences in the military were similar or slightly attenuated.
Racial disparities in stage at diagnosis were apparent in the DoD’s equal access healthcare system among older non-active duty beneficiaries. Socioeconomic status, supplemental insurance, cultural beliefs and biological factors may be related to these results.
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.
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.
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.
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.
Health status; Quality of life; Testicular cancer
Increases in thyroid papillary carcinoma incidence rates have largely been attributed to heightened medical surveillance and improved diagnostics. We examined papillary carcinoma incidence in an equal-access healthcare system by demographics, which are related to incidence.
Incidence rates during 1990-2004 among white and black individuals aged 20-49 years in the military and the general U.S. population were compared using data from the Department of Defense’s Automated Central Tumor Registry and the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER-9) program.
Incidence was significantly higher in the military than in the general population among white women [incidence rate ratio (IRR)=1.42, 95% 95% confidence interval (CI)=1.25-1.61], black women (IRR=2.31, 95% CI=1.70-2.99), and black men (IRR=1.69, 95% CI=1.10-2.50). Among whites, differences between the two populations were confined to rates of localized tumors (women: IRR=1.73, 95% CI=1.47-2.00; men: IRR=1.51, 95% CI=1.30-1.75), which may partially be due to variation in staging classification. Among white women, rates were significantly higher in the military regardless of tumor size, and rates rose significantly over time both for tumors ≤2 cm (military: IRR=1.64, 95% CI=1.18-2.28; general population: IRR=1.55, 95% CI=1.45-1.66) and >2 cm (military: IRR=1.74, 95% CI=1.07-2.81; general population: IRR=1.48, 95% CI=1.27-1.72). Among white men, rates increased significantly only in the general population. Incidence also varied by military service branch.
Heightened medical surveillance does not appear to fully explain the differences between the two populations or the temporal increases in either population.
These findings suggest the importance of future research into thyroid cancer etiology.
Thyroid Neoplasms; Incidence; SEER Program; Military Personnel; United States/epidemiology
Seminomas and nonseminomas (embryonal carcinomas, yolk sac tumors, teratomas, choriocarcinomas, mixed germ cell tumors) are the major histologic types of testicular germ cell tumors (TGCT). TGCTs composed of both seminomatous and nonseminomatous elements have been coded as their nonseminoma component in the World Health Organization (WHO) classification. In the late 1980's, a provisional International Classification of Diseases for Oncology (ICD-O) morphology code for mixed germ cell tumors was introduced. Using data from the Surveillance, Epidemiology and End Results (SEER) Program and two population-based German cancer registries, we examined the impact of MGCT classification on TGCT trends. Cases were identified using ICD-O topography (ICD-9: 186; ICD-10: C62) and morphology codes (seminoma = 9060-9062, 9064; embryonal carcinoma = 9070; yolk sack tumor = 9071; teratoma = 9080-9084, 9102; choriocarcinoma = 9100, 9101; MGCT = 9085; all nonseminoma = 9065-9102). As MGCTs and teratoma are often grouped as a single histologic group, we analyzed teratoma both including and excluding MGCTs. Between 1988 and 2007, incidence rates of MGCT in the U.S. increased 407%. Rates of teratoma including MGCT increased 80% while rates of teratoma excluding MGCT decreased 71%. Rates of embryonal carcinoma [-40%] and choriocarcinoma [-22%] also declined, suggesting that the code for MGCT is now being used for any mixed histology. Similar declines in incidence were observed in the German comparison populations. The declines in incidence of teratoma (excluding MGCT), embryonal carcinoma and choriocarcinoma in the US data since 1988 are likely due, in part, to increases in classifying any TGCT with mixed histology as MGCT. These results suggest that analysis of trends in specific histologic types of nonseminoma should be interpreted cautiously.
testicular germ cell tumors; mixed germ cell tumors; histology; incident trends
Cryptorchidism, hypospadias, subfertility, and testicular germ-cell tumor have been suggested to comprise a testicular dysgenesis syndrome (TDS) based on the premise that each may derive from perturbations of embryonal programming and gonadal development during fetal life. Endocrine-disrupting chemicals have been hypothesized to be associated with these disorders given the importance of sex steroid hormones in urogenital development and homeostasis. Organochlorines are one such set of compounds which are defined as containing between one and ten covalently bonded chlorine atoms. These compounds are persistent pollutants with long half-lives, accumulate in adipose tissue when ingested, bioaccumulate and biomagnify, and have complex and variable toxicological profiles. Examples of organochlorines include dichlorodiphenyltrichloroethane (DDT) and its metabolites, polychlorinated biphenyls (PCBs) and chlordane. In this comprehensive review of human epidemiologic studies which have tested for associations between organochlorines and facets of TDS, we find evidence for associations between the exposures p,p′-DDE, cis-nonachlor, and trans-nonachlor with TGCT. The sum of the evidence from human epidemiologic studies does not indicate any association between specific organochlorines studied and cryptorchidism, hypospadias, or fertility. Many other endocrine-disrupting chemicals, including additional organochlorines, have yet to be assessed in relation to disorders associated with TDS, yet study of such chemicals has strong scientific merit given the relevance of such hypotheses to urogenital development.
Cryptorchidism; Hydrocarbons, Chlorinated; Hypospadias; Infertility; Review; Testicular Neoplasms
Previous research has noted higher cancer mortality rates and lower survival among males than females. However, systematic comparisons of these two metrics by sex has been limited.
We extracted U.S. vital rates and survival data from the Surveillance, Epidemiology and End Results Database for 36 cancers by sex and age for the period 1977–2006. We compared sex-specific mortality rates and male-to-female mortality rate ratios (MRRs). We also extracted case data which included age and date of diagnosis, sex, primary cancer site, tumor stage and grade, survival time, vital status, and cause of death. Relative cancer-specific hazard ratios (HRs) for death in the 5-year period following diagnosis were estimated with Cox proportional hazards models, adjusted for covariates.
For the vast majority of cancers, age-adjusted mortality rates were higher among males than females with the highest male-to-female MRR for lip (5.51), larynx (5.37), hypopharynx (4.47), esophagus (4.08) and urinary bladder (3.36). Cancer-specific survival was, for most cancers, worse for males than females, but such disparities were drastically less than corresponding MRRs; e.g., lip (HR = 0.93), larynx (1.09), hypopharynx (0.98), esophagus (1.05), and urinary bladder (0.83).
Male-to-female MRRs differed markedly while cancer survival disparities were much less pronounced. This suggests that sex-related cancer disparities are more strongly related to etiology than prognosis.
Future analytical studies should attempt to understand causes of observed sex disparities in cancer.
Sex; Male; Female; SEER program; Neoplasms; Mortality; Epidemiology
Background Previously, we have shown that increasing adult height is associated with increased risk of testicular germ-cell tumor (TGCT). Recently, a number of single nucleotide polymorphisms (SNPs) have been found to be related to height. We examined whether these SNPs were associated with TGCT and whether they explained the relationship between height and TGCT.
Methods We genotyped 15 height-related SNPs in the US Servicemen’s Testicular Tumor Environmental and Endocrine Determinants (STEED) case–control study. DNA was extracted from buccal cell samples and Taqman assays were used to type the selected SNPs. We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs).
Results There were 561 cases and 676 controls for analysis. Two SNPs were found to be associated with risk of TGCT, rs6060373 (CC vs TT, OR = 1.51, 95% CI: 1.06–2.15) and rs143384 (CC vs TT, OR = 1.53, 95% CI: 1.09–2.15). rs6060373 is an intronic polymorphism of ubiquinol-cytochrome c reductase complex chaperone (UQCC), and rs143384 is a 5′UTR polymorphism of growth differentiation factor 5 (GDF5). No individual SNP attenuated the association between height and TGCT. Adjustment for all SNPs previously associated with adult height reduced the associations between adult height and TGCT by ~8.5%, although the P-value indicated only weak evidence that this difference was important (P = 0.26).
Conclusions This novel analysis provides tentative evidence that SNPs which are associated with adult height may also share an association with risk of TGCT.
Body height; case–control studies; epidemiology; polymorphism; single nucleotide; testicular neoplasms
Background: The etiologies of the male urogenital anomalies—cryptorchidism and hypospadias—are poorly understood. Given positive associations between chlordane isomers and testicular germ cell tumors, it is reasonable to assume that chlordanes might also be associated with other testicular dysgenesis syndrome disorders, namely cryptorchidism and hypospadias.
Objective: To examine whether exposure to in utero chlordane is related to cryptorchidism and hypospadias, we evaluated levels of chlordane derivatives, trans-nonachlor and oxychlordane, among pregnant women enrolled in the Collaborative Perinatal Project (CPP).
Methods: From 1959 to 1965, the CPP enrolled pregnant women at 12 U.S. medical centers. We analyzed serum trans-nonachlor and oxychlordane levels measured in third-trimester serum from the mothers of 217 sons with cryptorchidism, 197 sons with hypospadias, and 557 sons with neither condition. Adjusted odds ratios (ORs) and 95% confidence intervals were calculated using conditional logistic regression.
Results: The quartile-specific ORs for cryptorchidism or hypospadias show no notable associations with trans-nonachlor or oxychlordane. Further, there were no significant trends with increasing quartile of maternal trans-nonachlor or oxychlordane level in either cryptorchidism or hypospadias (p-trend all > 0.45).
Conclusions: The results do not support an association between chlordane levels and cryptorchidism or hypospadias. It is unlikely that current chlordane exposure is related to the development of either anomaly, given that serum chlordane levels at the time of sample collection, the early 1960s, were considerably higher than levels at present.
chlordanes; cryptorchidism; hypospadias; oxychlordane; pregnant women; prospective cohort; trans-nonachlor