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
Since the early 1970's the incidence of testicular germ cell tumors (TGCT) in the U.S. has been increasing, however, potential environmental exposures accounting for this rise have not been identified. A prior study reported a significant association among frequent and long-term current users of marijuana and TGCT risk. We aimed to evaluate the relationship of marijuana use and TGCT in a hospital-based case-control study conducted at The University of Texas M. D. Anderson Cancer Center.
TGCT cases diagnosed between January 1990 and October 1996 (n=187) and male friend controls (n=148) were enrolled in the study. All participants were between the ages of 18 and 50 at the time of cases' diagnosis and resided in Texas, Louisiana, Arkansas, or Oklahoma. Associations of marijuana use and TGCT were estimated using unconditional logistic regression, adjusting for age, race, prior cryptorchidism, cigarette smoking and alcohol intake.
Overall, TGCT cases were more likely to be frequent marijuana users (daily or greater) than were controls [OR: 2.2, 95% CI: 1.0, 5.1]. In the histologic-specific analyses nonseminoma cases were significantly more likely than controls to be frequent users [OR: 3.1, 95% CI: 1.2, 8.2] and long-term users (10+ years) [OR: 2.4, 95% CI: 1.0, 6.1].
Our finding of an association between frequent marijuana use and TGCT, particularly among men with nonseminoma, is consistent with the findings of a previous report. Additional studies of marijuana use and TGCT are warranted, especially studies evaluating the role of endocannabinoid signaling and cannabinoid receptors in TGCT.
marijuana use; seminomas; nonseminomas; testicular germ cell tumors; hospital-based case-control
Prior studies of cancer risk among diabetic men have reported inconsistent findings. The aim of the current investigation was to assess the risk of cancer among a large cohort (n=4,501,578) of black and white U.S. veterans admitted to Veterans Affairs hospitals. The cancer risk among men with diabetes (n=594,815) was compared to the risk among men without diabetes (n=3,906,763). Poisson regression was used to estimate adjusted relative risks (RRs) and 95% confidence intervals (CIs). Overall, men with diabetes had a significantly lower risk of cancer (RR=0.93, 95%CI=0.93-0.94). Men with diabetes, however, had increased risks of cancers of the liver (RR=1.95, 95%CI=1.82-20.9), pancreas (RR=1.50, 95%CI=1.42-1.59), biliary tract (RR=1.41, 95%CI=1.22-1.62), colon (RR=1.20, 95%CI=1.16-1.25), rectum (RR=1.12, 95%CI=1.07-1.18), and kidney (RR=1.09, 95%CI=1.03-1.16), as well as leukemia (RR=1.14, 95%CI=1.08-1.21) and melanoma (RR=1.13, 95%CI=1.03-1.24). In contrast, men with diabetes had decreased risks of cancers of the prostate (RR=0.89, 95%CI=0.87-0.91), brain (RR=0.91, 95%CI=0.81-0.99), buccal cavity (RR=0.85, 95%CI=0.82-0.89), lung (RR=0.79, 95%CI=0.77-0.80), esophagus (RR=0.77, 95%CI=.072-0.82), and larynx (RR=0.76, 95%CI=0.71-0.80). These findings indicate that black and white men with diabetes are at significantly lower risk of total cancer and of two of the most common cancers among U.S. males; lung and prostate cancers. These decreased risks were offset, however, by increased risks of cancer at several sites. Hyperinsulinemia may explain the increased risks of the digestive cancers, while lower testosterone levels, in the case of prostate cancer, and higher BMI, in the case of lung cancer, may explain the decreased risks of those tumors.
Background We undertook a systematic review and meta-analysis of perinatal variables in relation to testicular cancer risk, with a specific focus upon characteristics of the son.
Methods Literature databases Scopus, EMBASE, PubMed and Web of Science were searched using highly sensitive search strategies. Of 5865 references retrieved, 67 articles met the inclusion criteria, each of which was included in at least one perinatal analysis.
Results Random effects meta-analysis produced the following results for association with testicular cancer risk: birth weight [per kilogram, odds ratio (OR) = 0.94, 95% confidence interval (CI) 0.88–1.01, I2 = 12%], low birth weight (OR = 1.34, 95% CI 1.08–1.67, I2 = 51%), high birth weight (OR = 1.05, 95% CI 0.96–1.14, I2 = 0%), gestational age (per week, OR = 0.95, 95% CI 0.92–0.98, I2 = 38%; low vs not, OR = 1.31, 95% CI 1.07–1.59, I2 = 49%), cryptorchidism (OR = 4.30, 95% CI 3.62–5.11, I2 = 44%), inguinal hernia (OR = 1.63, 95% CI 1.37–1.94, I2 = 38%) and twinning (OR = 1.22, 95% CI 1.03–1.44, I2 = 22%). Meta-analyses of the variables birth length, breastfeeding and neonatal jaundice did not provide evidence for an association with testicular cancer risk. When low birth weight was stratified by data ascertainment (record/registry vs self-report), only the category of self-report was indicative of an association. Meta-regression of data ascertainment (record/registry vs self-report) inferred that record-/registry-based studies were less supportive of an association with gestational age (per week = 0.97, 95% CI 0.94–1.00, I2 = 29%; low vs not = 1.08, 95% CI 0.91–1.28, I2 = 32%).
Conclusion In conclusion, this systematic review and meta-analysis finds evidence that cryptorchidism, inguinal hernia and twinning, and tentative evidence that birth weight and gestational age, are associated with risk of testicular cancer.
Epidemiology; meta-analysis; pregnancy; review; systematic; testicular neoplasms
Several plausible mechanisms, including fat, iron, heterocyclic amines, and N-nitroso compounds, link meat intake with chronic liver disease (CLD) and hepatocellular carcinoma (HCC). Few studies have investigated these associations.
We prospectively examined the relationship between meat and associated exposures with CLD mortality (n = 551; not including HCC) and HCC incidence (n = 338) in 495 006 men and women of the National Institutes of Health–AARP Diet and Health Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the fifth (Q5) vs the first (Q1) quintile were estimated from multivariable adjusted Cox proportional hazards regression models. All tests of statistical significance were two-sided.
We found inverse associations between white meat and risk of CLD (HR = 0.52, 95% CI = 0.39 to 0.70, 7.5 vs 18.2 cases per 100 000 person-years) and HCC (HR = 0.52, 95% CI = 0.36 to 0.77, 5.8 vs 14.3 cases per 100 000 person-years). Red meat was associated with higher risk of CLD (HR = 2.59, 95% CI = 1.86 to 3.61, 22.3 vs 6.2 cases per 100 000 person-years) and HCC (HR = 1.74, 95% CI = 1.16 to 2.61, 14.9 vs 5.7 cases per 100 000 person-years). Among fat types, results were strongest for saturated fat (for CLD, HR = 3.50, 95% CI = 2.48 to 4.96, 23.0 vs 6.5 cases per 100 000 person-years; for HCC, HR = 1.87, 95% CI = 1.23 to 2.85, 14.5 vs 6.3 cases per 100 000 person-years). After mutual adjustment, risk estimates persisted for saturated fat, red meat, and white meat. Heme iron, processed meat, nitrate, and nitrite were positively associated with CLD but not with HCC. Individual heterocyclic amines, 2-amino-3,4,8-trimethylimidazo[4,5,-f]quinoxaline (DiMeIQx), 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), and 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP), were not associated with either outcome.
Our results suggest that red meat and saturated fat may be associated with increased CLD and HCC risk, whereas white meat may be associated with reduced risk.
It has been hypothesized that the increased prevalence of testicular germ cell tumors (TGCT) may be attributable to endocrine disrupting chemicals, such as persistent organic pollutants (POPs); these may be modulated by hormone-metabolizing enzymes. Using data from 568 cases and 698 controls enrolled in the U.S. Servicemen’s Testicular Tumor Environmental and Endocrine Determinants Study, we examined associations between TGCT and POPs, including p,p′-DDE, chlordane-related compounds, and polychlorinated biphenyls (PCBs), modified by polymorphisms in 5 hormone-metabolizing genes (CYP17A1, CYP1A1, HSD17B1, HSD17B4, and AR). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models that stratified associations of POP exposure and TGCT risk by genotype. Two polymorphisms in CYP1A1, rs1456432 and rs7495708, modified the association between trans-nonachlor and total chlordanes and TGCT risk. Among men with a minor allele for rs1456432, those with the highest quartiles had an increased risk of TGCT (OR=1.90, 95% CI, 1.01–3.56) compare to those with the lowest; there were no increased risk among men with the homozygous major allele genotype (p-interaction=0.024). Similar results were seen for rs7495708. HSD17B4 rs384346 modified the associations between TGCT risk and PCB-118 and PCB-138 concentrations: the 45–55% reductions in TGCT risk for men with the highest quartiles compared to the lowest quartiles were only present in those who had a major homozygous allele genotype (p-interactions<0.04). Thus, there are suggestions that certain CYP1A1 and HSD17B4 polymorphisms may modify the associations between POPs and TGCT risk. With false discovery rate values >0.2, however, caution is advisable when interpreting the findings of this study.
polychlorinated biphenyls; persistent organochlorine pesticides; testicular germ cell tumors; hormone-metabolizing genes
While testicular cancer incidence rates have been widely reported in populations of Northern European ancestry, rates in other population have been less frequently examined. In a prior report, global testicular cancer incidence rates and trends for the years 1973–1997 were summarized. The current report extends these analyses with an additional 5 years of data from Cancer Incidence in Five Continents.
Age-standardized incidence rates over successive 5-year time periods were obtained for populations in the Americas, Asia, Europe, and Oceania.
In general, testicular cancer incidence remained highest in Northern European populations (8.0–9.0 per 100,000) and lowest in Asian and African populations (<1 per 100,000). One notable exception to this pattern, however, was the very high rate reported by the Valdivia, Chile registry (8.8 per 100,000). In many populations, incidence rates rose between 1973 and 2002, although the increases were strongest and most consistent among populations of European ancestry. In some European populations, such as those of Denmark and of Geneva, Switzerland, some plateauing of rates was evident in recent years. There was little evidence of increase and possible evidence of modest decline in rates in east Asian populations. In general, the trends by histology (seminoma, nonseminoma) were similar to one another.
Risk of testicular cancer remains high in Northern European populations and low in Asian and African populations. Reasons for increasing rates among Northern Europeans and more stable or declining rates among East Asians are unexplained, supporting the need for future etiologic studies.
testicular cancer; trends; seminoma; nonseminoma
To compare oral contraceptive (OC) use during a 12-month period among women aged 18–39 years in the U.S. military and the general U.S. population using data from the Military Health System Management Analysis and Reporting Tool (M2) and the National Health and Nutrition Examination Survey (NHANES), respectively.
OC use was age adjusted to the 2000 U.S. Census population. Comparisons between the military (n = 83,181) and the general population (unweighted n = 360), as well as between the military branches, were conducted overall and stratified by age, race/ethnicity, and marital status.
OC use was higher in the military (34%) than in the general population (29%, p < 0.05). This difference increased with age and was most pronounced among Hispanics (military, 32.2%; general population, 19.8%). Within the military, OC use was highest in the Air Force (39%) and lowest in the Army (30%, p < 0.05).
These findings suggest that OC use differs between the military and the general population and within the military by service branch. Further studies that assess whether OC use is related to variations in health outcomes between these two populations and within the military are warranted.
Though incidence of colorectal cancer (CRC) in the US, has declined in recent years, rates remain higher in men than women and the male-to-female incidence rate ratio (MF IRR) increases progressively across the colon from the cecum to the rectum. Rates among races/ethnicities other than Whites or Blacks have not been frequently reported. To examine CRC rates by sex across anatomic subsite, age, and racial/ethnic groups, we used the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program for cases diagnosed among residents of 13 registries during 1992–2006. Incidence rates were expressed per 100,000 person-years and age-adjusted to the 2000 US Standard Population; MF IRR and 95% confidence intervals were also calculated. Among each racial/ethnic group, the MF IRR increased fairly monotonically from close to unity for cecal cancers to 1.81 (Hispanics) for rectal cancers. MF IRRs increased with age most rapidly for distal colon cancers from <1.0 at ages <50 years to 1.4–1.9 at older ages. The MF IRR for rectal cancers also rose with age from about 1.0 to 2.0. For proximal cancer, the MF IRR was consistently <1.5; among American Indian/Alaska Natives it was <1.0 across all ages. The MF IRRs for CRC vary markedly according to subsite and age but less by racial/ethnic group. These findings may partially reflect differences in screening experiences and access to medical care but also suggest that etiologic factors may be playing a role.
colorectal cancer; sex ratio; incidence; SEER program; epidemiology; neoplasms