Causal inference multiple imputation investigation of the impact of cannabinoids and other substances on ethnic differentials in US testicular cancer incidence.

BACKGROUND: Ethnic differences in testicular cancer rates (TCRs) are recognized internationally. Cannabis is a known risk factor for testicular cancer (TC) in multiple studies with dose-response effects demonstrated, however the interaction between ancestral and environmental mutagenic effects has not been characterized. We examined the effects of this presumed gene-environment interaction across US states. METHODS: State based TCR was downloaded from the Surveillance Epidemiology and End Results (SEER) website via SEERStat. Drug use data for cigarettes, alcohol use disorder, analgesics, cannabis and cocaine was taken from the National Survey of Drug Use and Health a nationally representative study conducted annually by the Substance Abuse and Mental Health Services Administration (SAMHSA) with a 74.1% response rate. Cannabinoid concentrations derived from Drug Enforcement Agency publications. Median household income and ethnicity data (Caucasian-American, African-American, Hispanic-American, Asian-American, American-Indian-Alaska-Native-American, Native-Hawaiian-Pacific-Islander-American) was from the US Census Bureau. Data were processed in R using instrumental regression, causal inference and multiple imputation. RESULTS: 1975-2017 TCR rose 41% in African-Americans and 78.1% in Caucasian-Americans; 2003-2017 TCR rose 36.1% in Hispanic-Americans and 102.9% in Asian-Pacific-Islander-Americans. Ethnicity-based scatterplot-time and boxplots for cannabis use and TCR closely mirrored each other. At inverse probability-weighted interactive robust regression including drugs, income and ethnicity, ethnic THC exposure was the most significant factor and was independently significant (ß-estimate = 4.72 (2.04, 7.41), P = 0.0018). In a similar model THC, and cannabigerol were also significant (both ß-estimate = 13.87 (6.33, 21.41), P = 0.0017). In additive instrumental models the interaction of ethnic THC exposure with Asian-American, Hispanic-American, and Native-Hawaiian-Pacific-Islander-American ethnicities was significant (ß-estimate = - 0.63 (- 0.74, - 0.52), P = 3.6 × 10- 29, ß-estimate = - 0.25 (- 0.32, - 0.18), P = 4.2 × 10- 13, ß-estimate = - 0.19 (- 0.25, - 0.13), P = 3.4 × 10- 9). After multiple imputation, ethnic THC exposure became more significant (ß-estimate = 0.68 (0.62, 0.74), P = 1.80 × 10- 92). 25/33 e-Values > 1.25 ranging up to 1.07 × 105. Liberalization of cannabis laws was linked with higher TCR's in Caucasian-Americans (ß-estimate = 0.09 (0.06, 0.12), P = 6.5 × 10- 10) and African-Americans (ß-estimate = 0.22 (0.12, 0.32), P = 4.4 × 10- 5) and when dichotomized to illegal v. others (t = 6.195, P = 1.18 × 10- 9 and t = 4.50, P = 3.33 × 10- 5). CONCLUSION: Cannabis is shown to be a TC risk factor for all ethnicities including Caucasian-American and African-American ancestries, albeit at different rates. For both ancestries cannabis legalization elevated TCR. Dose-response and causal relationships are demonstrated.

Assessment of Prognostic Factors of Racial Disparities in Testicular Germ Cell Tumor Survival in the United States (1992-2015).

OBJECTIVE: Testicular germ cell tumors (TGCT) are the most common cancer among men aged 15 to 39 years. Previous studies have considered factors related to TGCT survival rate and race/ethnicity, but histological type of the diagnosed cancer has not yet been thoroughly assessed. METHODS: The data came from 42,854 eligible patients from 1992 to 2015 in the Surveillance Epidemiology and End Results 18. Frequencies and column percent by seminoma and nonseminoma subtypes were determined for each covariates. We used Cox proportional hazard regression to assess the impact of multiple factors on post-diagnostic mortality of TGCT. RESULTS: Black males were diagnosed at a later stage, more commonly with local or distant metastases. The incidence of TGCT in black non-seminoma tumors increased most significantly. The difference in survival rates between different ethnic and histological subtypes, overall survival (OS) in patients with non-seminoma was significantly worse than in patients with seminoma. The most important quantitative predictor of death was the stage at the time of diagnosis, and older diagnostic age is also important factor affecting mortality. CONCLUSION: Histological type of testicular germ cell tumor is an important factor in determining the prognosis of testicular cancer in males of different ethnic groups.

Development and validation of prognostic nomogram for germ cell testicular cancer patients.

The purpose of our study was to establish a reliable and practical nomogram based on significant clinical factors to predict the overall survival (OS) and cancer-specific survival (CSS) of patients with germ cell testicular cancer (GCTC). Patients diagnosed with GCTC between 2004 and 2015 were obtained from the SEER database. Nomograms were constructed using the R software to predict the OS and CSS probabilities and the constructed nomograms were validated and calibrated. A total of 22,165 GCTC patients were enrolled in the study, including the training cohort (15,515 patients) and the validation cohort (6,650 patients). In the training cohort, multivariate Cox regression showed that age, race, AJCC stage, SEER stage and surgery were independent prognostic factors for OS, while age, race, AJCC stage, TM stage, SEER stage and radiotherapy were independent prognostic factors for CSS. Based on the above Cox regression results, we constructed prognostic nomograms of OS and CSS in GCTC patients and found that the OS nomograms had higher C-index and AUC compared to TNM stage in the training and validation cohorts. In addition, in the training and external validation cohorts, the calibration curves showed a good consistency between the predicted and actual 3-, 5- and 10-year OS and CSS rates of the nomogram. The current prognostic nomogram can provide a personalized risk assessment for the survival of GCTC patients.

Testicular cancer in Hispanics: incidence of subtypes over time according to neighborhood sociodemographic factors in California.

PURPOSE: Hispanic men in the USA experience the second-highest incidence rate of testicular germ cell tumors (TGCTs), behind non-Hispanic (NH) White men, and have experienced steep increases in TGCT in recent decades. It is unknown whether increases in incidence differ according to neighborhood sociodemographic factors. METHODS: We conducted a population-based study of n = 3759 Hispanic and n = 8469 NH White men (n = 12,228 total) diagnosed with TGCT in California during the three most recent pericensal periods. We calculated incidence rates according to neighborhood socioeconomic status (nSES) and among Hispanics, according to ethnic enclave. We calculated incidence rate ratios to compare rates across nSES and ethnic enclave and to examine changes in rates over pericensal time periods according to these neighborhood factors for major histologic types (i.e., seminoma and nonseminoma). RESULTS: Hispanic men residing in high SES, compared to low SES, neighborhoods had greater incidence of seminoma and nonseminoma testicular cancer across pericensal periods, as did Hispanic men in low enclave (less ethnic), compared to high enclave, neighborhoods. Between the periods 1998-2002 and 2008-2012, Hispanic men residing in low SES neighborhoods experienced a 39% increased incidence of seminoma, while those residing in low and middle SES neighborhoods experienced 87% and 48% increased incidence of nonseminoma, respectively. CONCLUSION: While TGCT incidence has increased among all Hispanic men, incidence increases appear to be driven disproportionately by those residing in lower SES and lower enclave neighborhoods, particularly for nonseminoma.

Testicular Cancer Incidence and Mortality in New Mexico.

Objective: To examine incidence and survival of testicular cancer in New Mexico, overall and separately for border and non-border counties. Methods: Incidence and 5-year survival rates for testicular cancer were obtained from the SEER18 database using the SEER*Stat program following established NCI protocols. Incidence data were compared using Student's t-test. Age-adjusted 5-year survival and Kaplan-Meier method were used to estimate survival. Log-rank tests were used to compare survival for New Mexico to the remaining17 geographical areas of the SEER 18 and for the New Mexico border counties to the New Mexico non-border counties. Odds ratios were used to compare testicular stage at diagnosis. Cox proportional hazards regression was performed to account for race/ethnicity, and border status. Results: From 2000-2015, New Mexico had a testicular cancer incidence rate of 6.3 per 100,000 people, significantly higher than SEER18 (P<.001). The 5-year survival rate in New Mexico did not differ significantly from the SEER18 (P=.3). Border Hispanics had a lower survival rate than border non-Hispanic populations (P=.03). From 2000-2018, New Mexico had a significantly higher proportion of distant cancers than the SEER18 (OR: 1.29, 95% CI: 1.08 to 1.53, P=.005). Conclusions: The higher incidence of testicular cancer in New Mexico does not appear to have a clear explanation based on the current understanding of risk factors; however, the increased incidence in New Mexico does not appear to be associated with increased mortality. The higher proportion of advanced testicular cancers in New Mexico may represent a delay in diagnosis. The increased mortality rate seen in Hispanic border populations may be due in part to barriers to care.

Association between KITLG Gene Polymorphisms and Testicular Germ Cell Tumors: A Systematic Review and Meta-analysis.

It has been reported that c-KIT ligand (KITLG) gene polymorphisms may be associated with testicular germ cell tumors (TGCT). Owing to mixed and inconclusive results, we conducted a systematic review and meta-analysis to summarize and clarify this association. A systematic search of studies on the association between KITLG gene polymorphisms and TGCT susceptibility was conducted in databases. Odds ratios and 95% confidence intervals were used to pool the effect size. Six articles were included in our systematic review and meta-analysis. Compared with adenine (A), KITLG rs995030 guanine (G) might be associated with increased risk of TGCT. There are insufficient data to fully confirm the association between KITLG rs4474514 and TGCT susceptibility. Well-designed studies with larger sample size and more subgroups are required to validate the risk identified in the current meta-analysis.

Variable Features of Juvenile Polyposis Syndrome With Gastric Involvement Among Patients With a Large Genomic Deletion of BMPR1A.

OBJECTIVES: Loss-of-function mutations of BMPR1A cause juvenile polyposis syndrome (JPS), but large genomic deletions in BMPR1A are rare, reported in few families only, and data regarding the associated phenotype are limited. METHODS: We investigated clinical features and genomic data of 7 extended seemingly unrelated families with a genomic deletion of the entire coding region of BMPR1A. We defined mutation size, mutation prevalence, and tumor pathogenesis using whole-genome sequencing, targeted genotyping, and haplotype analysis. RESULTS: Patients with JPS from 7 families of Bukharin Jewish ancestry carried a deletion of 429 kb, encompassing the BMPR1A coding sequence and 8 downstream genes. Haplotype analysis and testing controls identified this as a common founder mutation occurring in 1/124 individuals of Bukharin origin. Tumor testing did not demonstrate loss of heterozygosity. Among carriers, JPS was almost fully penetrant, but clinical features varied widely, ranging from mild to very severe, including pan-enteric polyps, gastritis, and colorectal, esophageal, and testicular cancer, and carriers with phenotypes, which would not have raised suspicion of JPS. DISCUSSION: The phenotype in this large cohort was extremely variable, although all carriers shared the same variant and the same genetic background. New observations include a preponderance of adenomatous rather than juvenile polyps, possible association with testicular cancer, and unexpected upper gastrointestinal involvement.

The puzzling incidence of testicular cancer in New Zealand: what can we learn?

BACKGROUND: Testicular germ cell tumour is the most common cancer to be diagnosed among young men. In New Zealand, we have observed some puzzling trends in the epidemiology of this disease. METHODS: We have conducted a narrative review of available evidence regarding the puzzling epidemiology of testicular germ cell tumour in New Zealand and discussed the possible drivers of these trends. RESULTS AND DISCUSSION: Whereas testicular cancer is most commonly a disease of White men, in New Zealand it is the indigenous Maori population that suffer by far the greatest rate of disease (age-adjusted relative risk: 1.80, 95% CI 1.58-2.05). Even more curiously, the rate of testicular germ cell tumour among Maori men aged 15-44 (28/100,000) is substantially greater than for Pacific Island men (9/100,000), a rare example of divergence between these two populations in terms of the incidence of any disease (cancer or otherwise). Our observations beg the following questions: first, why are rates of testicular germ cell tumour so much higher among Maori New Zealanders compared to the already high rates observed among European/Other New Zealanders? Second, why are rates of testicular germ cell tumour so completely divergent between Maori and Pacific New Zealanders, when these two groups typically move in parallel with respect to the incidence of given diseases? Finally, what might we learn about the factors that cause testicular germ cell tumour in general by answering these questions? CONCLUSION: This review examines the possible drivers of our observed disparity, discusses their feasibility, and highlights new work that is underway to further understand these drivers.

Cancer Knowledge Among Mexican Immigrant Farmworkers in North Carolina.

Latino farmworkers are exposed to a number of carcinogens in the workplace. Cancer survival rates for Latinos are below average. This paper describes Mexican immigrant farmworkers' knowledge of colorectal, breast, and testicular cancer, and compares farmworkers' cancer knowledge to that of other Mexican immigrants. Survey interviews for this study were conducted with 100 farmworkers and 100 non-farmworkers in 2015 in North Carolina as part of an ongoing community-based participatory research project. We found low to moderate levels of knowledge about colorectal, breast, and testicular cancer among farmworkers. Compared to non-farmworkers, farmworkers had similar levels of knowledge about breast and testicular cancer, but slightly lower knowledge about colorectal cancer (p = 0.0087). Few studies have used quantitative methods to assess farmworkers' knowledge of specific types of cancer. Our results demonstrate a need for increased dissemination of existing cancer education programs and further research to develop additional educational tools.

Testicular Cancer in New Zealand (TCNZ) study: protocol for a national case-control study.

Testicular cancer (TC) is by far the most common cancer to affect young men; however, the exposures that cause this disease are still poorly understood. Our own research has shown that Maori men have the highest rates of this disease in New Zealand-a puzzling observation, since internationally TC is most commonly a disease of men of European ancestry. These trends provide us with a unique opportunity: to learn more about the currently unknown exposures that cause TC, and to explain why Maori have the highest rates of this disease in New Zealand. Using epidemiology and genetics, our experienced research team will conduct a nationwide study which aims to answer these internationally important questions. AIM OF STUDY: The overall aim of the current national case-control study is to identify the key exposures in the development of TC in New Zealand, and explore which factors might explain the difference in the incidence of TC between Maori and non-Maori. METHODS AND ANALYSIS: Outside of our own investigations into cryptorchidism, we still do not know which exposures are driving the significant incidence disparity between ethnic groups in NZ. The aim of the proposed research is to use a population-based case-control study to identify the key exposures in the development of TC in New Zealand. We will recruit 410 TC cases and 410 controls, and collect (1) environmental exposure data, via interview and (2) genetic information, via genome-wide genotyping. ETHICS AND DISSEMINATION: Ethical approval for this study was sought and received from the New Zealand Ministry of Health's Health and Disability Ethics Committee (reference # 17/NTA/248). Following a careful data interpretation process, we will disseminate the findings of this study to a wide and varied audience ranging from general academia, community groups and clinical settings, as well as to the participants themselves.

Update on epidemiologic considerations and treatment trends in testicular cancer.

PURPOSE OF REVIEW: We aim to give an overview of the epidemiology and treatment trends of testicular germ cell tumors (TGCTs), with an emphasis on recent trends. RECENT FINDINGS: The incidence of TGCT appears to be increasing, particularly in developed countries, although the reasons are not well understood. There is evidence of racial differences in predisposition to TGCT, with white men having highest risk and men of African or Asian descent having lower risk. In the United States, the incidence of TGCT among Hispanics appears to be rising most quickly. A recent genomic analysis indicates there is no highly penetrant major TGCT susceptibility gene. Incorporation of multidisciplinary care has led to excellent long-term cure rates; however, access to care and insurance remains barriers in young men. Recent treatment trends have centered on maximizing oncologic outcomes while minimizing long-term morbidity. SUMMARY: Emerging population-level data provide critical insight into the evolving demographics of TGCT, which may allow for elucidation of biologic and environmental determinants of TGCT. Further, identification of socioeconomic barriers to excellent clinical outcomes will allow for targeted interventions to patients with unique demographic and socioeconomic considerations. Treatment trend analyses suggest that the field is moving toward minimizing treatment-related morbidity.

Disparities in Access and Regionalization of Care in Testicular Cancer.

INTRODUCTION: Timely mobilization of specialized resources are needed to achieve optimal outcomes in testicular cancer. We used the National Cancer Database to investigate the hospital and demographic features driving disparity. PATIENTS AND METHODS: We identified adult men with testicular tumors diagnosed from 2004 to 2013. We a priori examined the association among race/ethnicity, socioeconomic status (SES), travel burden, hospital characteristics, and indicators of delays in testicular cancer care. The outcomes included large primary tumor, stage III at diagnosis, orchiectomy delay, and mortality. The analyses included multivariable Cox proportional hazards regression for time-dependent outcomes and logistic regression for categorical outcomes. RESULTS: Of 31,964 men, 29% had a large primary tumor, 17% presented with stage III disease, 10% experienced an orchiectomy delay, and 6% died. Black race or Hispanic ethnicity, low SES, and underinsurance were associated with poorer outcomes (P < .001 for all). Higher hospital volume, cancer center status, and lower travel burden were associated with improved outcomes (P < .001 for all). CONCLUSION: Nonwhite race/ethnicity, low SES, and underinsurance were associated with diminished access to testicular cancer care. Insurance status, a marker of SES, had the most consistent association with poor outcomes. This finding highlights the oncologic imperative to improve access to adequate health insurance. Regionalization of subspecialty care might, paradoxically, improve outcomes but also create additional barriers in the form of an added travel burden.

Small Numbers, Big Challenges: Adolescent and Young Adult Cancer Incidence and Survival in New Zealand.

PURPOSE: This study was undertaken to determine cancer survival and describe the unique spectrum of cancers diagnosed among New Zealand's adolescents and young adult (AYA) population. METHODS: Registrations for 1606 15-24 year olds diagnosed with a new primary malignant tumor between 2000 and 2009 were obtained from the New Zealand Cancer Registry and classified according to AYA diagnostic group and subgroup, age, sex, and prioritized ethnicity. Age-standardized incidence rates (IRs) per million person years and 5-year relative survival ratios were calculated. RESULTS: Cancer incidence was 228.6 per million for adolescents aged 15-19 years and 325.7 per million for young adults aged 20-24 years. Overall IRs were consistent across all ethnic groups but there were unique ethnic differences by tumor group including a higher incidence of bone tumors, carcinoma of the gastrointestinal tract, and gonadal germ cell tumors among Maori, a higher incidence of leukemia among Pacific peoples, and a higher incidence of melanoma among non-Maori/non-Pacific peoples. Five-year relative survival for adolescents (75.1%) and AYA overall (80.6%) appeared poorer than had been achieved in other high-income countries. Maori (69.5%) and Pacific (71.3%) AYA had lower 5-year survival compared to non-Maori/non-Pacific peoples (84.2%). CONCLUSION: The survival disparities observed require further investigation to identify and address the causes of these inferior outcomes. The newly established AYA Cancer Network Aotearoa has been tasked with improving cancer survival and care and ensuring equality of access for New Zealand AYAs with cancer.

Germ Cell Testicular Cancer Incidence, Latitude and Sunlight Associations in the United States and Australia.

International patterns suggest germ cell testicular cancer (GCTC) incidence may be lower in lower latitudes. To investigate this possibility, we examined GCTC incidence by latitude (population centroid in 2000) for men ≥15 years within two reasonably homogeneous countries, the United States and Australia. In the United States, we examined age-adjusted incidence/latitude trends using data from states (2001-2010) and local-area registries (1980-2011). In Australia, we evaluated incidence/latitude trends in 61 Statistical Divisions (2000-2009). In U.S. White men (68 566 cases), state incidences increased by latitude, rising 5.74% (4.45-7.05%) per 5°North latitude increment. Similar trends were found for seminoma and nonseminoma subtypes (P < 0.001). In U.S. Black men (2256 cases), the association was also seen (4.9%; 0.2-9.7%). In local U.S. data, similar increases in incidence with latitude were present in each of the last three decades. In Australia (6042 cases), the incidence increased by 4.43% (95% CI: 1.54-7.39%) per 5°South, and trends for subtypes were similar. Thus, we found that incidence of GCTC in both White and Black men increased significantly with distance from the equator, approximately 1% per degree within the range of latitudes studied.

Disparities in Adolescent and Young Adult Survival After Testicular Cancer Vary by Histologic Subtype: A Population-Based Study in California 1988-2010.

PURPOSE: Testicular cancer is the most common cancer among adolescent and young adult (AYA) men 15-39 years of age. This study aims to determine whether race/ethnicity and/or neighborhood socioeconomic status (SES) contribute independently to survival of AYAs with testicular cancer. METHODS: Data on 14,249 eligible AYAs with testicular cancer diagnosed in California between 1988 and 2010 were obtained from the population-based California Cancer Registry. Multivariable Cox proportional hazards regression was used to examine overall and testicular cancer-specific survival and survival for the seminoma and nonseminoma histologic subtypes according to race/ethnicity, census-tract level neighborhood SES, and other patient and clinical characteristics. RESULTS: Compared with White AYAs, Hispanic AYAs had worse overall and testicular cancer-specific survival (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.07-1.37) and Black AYAs had worse overall survival (HR, 1.41; 95% CI, 1.01-1.97), independent of neighborhood SES and other demographic and clinical factors. Racial/ethnic disparities in survival were more pronounced for nonseminoma than for seminoma. AYAs residing in middle and low SES neighborhoods experienced worse survival across both histologic subtypes independent of race/ethnicity and other factors, while improvements in survival over time were more pronounced for seminoma. Longer time to treatment was also associated with worse survival, particularly for AYAs with nonseminoma. CONCLUSION: Among AYAs, race/ethnicity, and neighborhood SES are independently associated with survival after testicular cancer. Variation in disparities by histologic type according to demographic factors, year of diagnosis, and time to treatment may reflect differences in prognosis and extent of treatment for the two histologies.

Treatment Trends for Stage I Testicular Seminoma in an Equal-Access Medical System.

BACKGROUND: The practice patterns for adjuvant therapies for stage I seminoma are rapidly evolving, and surveillance is currently preferred. How these recommendations have affected contemporary practice in an equal-access US population is unknown. MATERIALS AND METHODS: A total of 436 men diagnosed with clinical stage IA-IB seminoma from 2001 to 2011 were identified in the Automated Central Tumor Registry (ACTUR). The ACTUR is the cancer registry system for the Department of Defense. Logistic regression models analyzed the association between patient characteristics and adjuvant therapy. Overall and recurrence-free survival were determined from Kaplan-Meier analysis. RESULTS: The use of adjuvant radiotherapy in this population decreased significantly from 2001 to 2011. In 2001, 83.9% of patients received radiotherapy compared with only 24.0% in 2011. During that period, a concomitant increase occurred in the use of chemotherapy from 0% to 38.0%. A later year of diagnosis was significantly associated with a greater rate of receiving chemotherapy relative to radiotherapy (P < .001 for 2006-2011 vs. 2001-2005; relative rate ratio, 19.3; 95% confidence interval [CI], 8.04-46.13). A later year of diagnosis was not significantly associated with the receipt of surveillance (P = .412 for 2006-2011 vs. 2001-2005; odds ratio, 0.83; 95% CI, 0.54-1.29). Black race or age was not significantly associated with adjuvant therapy. With a median follow-up period of 4.7 years, the 5-year overall and recurrence-free survival rates were 98.0% and 77.0%, respectively. CONCLUSION: The use of adjuvant radiotherapy has been replaced by chemotherapy for clinical stage I testicular seminoma in an equal-access system. The lack of an increase in active surveillance in our cohort might represent overtreatment of the population.

Incidence of testicular germ cell tumors among US men by census region.

BACKGROUND: The incidence of testicular germ cell tumors (TGCTs) in the United States is notably higher among white men versus other men. Previously, however, it was reported that rates were rising among Hispanics in certain areas. To determine whether this finding was evident in a wider area of the United States, data from 39 US cancer registries were examined. METHODS: Racial/ethnic-specific incidence rates per 100,000 man-years were calculated overall and by census region for the period of 1998-2011. Annual percentage changes (APCs) were estimated, and joinpoint models were fit. Differences in incidence by region were examined with the Wald test. RESULTS: From 1998 to 2011, 88,993 TGCTs were recorded. The TGCT incidence was highest among non-Hispanic whites (6.57 per 100,000), who were followed by Hispanics (3.88), American Indians/Alaska Natives (2.88), Asians/Pacific Islanders (A/PIs; 1.60), and non-Hispanic blacks (1.20). The incidence significantly increased among Hispanics (APC, 2.31; P < .0001), with rates rising in all regions except the South. Rates rose slightly among non-Hispanic whites (APC, 0.51; P = .0076). Significant differences in rates by region were seen for Hispanics (P = .0001), non-Hispanic whites (P < .0001), and A/PIs (P < .0001), with the highest rates among Hispanics in the West and with the highest rates among non-Hispanic whites and A/PIs in the Northeast. CONCLUSIONS: Although the incidence of TGCTs remained highest among non-Hispanic whites between 1998 and 2011, the greatest increase was experienced by Hispanics. Rising rates of TGCTs among Hispanics in the United States suggest that future attention is warranted. Reasons for the increase may include variability in birthplace, changing exposures, genetic susceptibility, and the length of US residence.

Recent trends in the incidence of testicular germ cell tumors in the United States.

Testicular germ cell tumors (TGCT), which comprise 98% of all testicular malignancies, are the most commonly occurring cancers among men between the ages of 15 and 44 years in the United States (US). A prior report from our group found that while TGCT incidence among all US men increased between 1973 and 2003, the rate of increase among black men was more pronounced starting in 1989-1993 than was the rate of increase among other men. In addition, TGCT incidence increased among Hispanic white men between 1992 and 2003. To determine whether these patterns have continued, in the current study, we examined temporal trends in incidence through 2011. Between 1992 and 2011, 21 271 TGCTs (12 419 seminomas; 8715 non-seminomas; 137 spermatocytic seminomas) were diagnosed among residents of the Surveillance, Epidemiology, and End Results 13 registry areas. The incidence of TGCT was highest among non-Hispanic white men (6.97 per 100 000 man-years) followed by American Indian/Alaska Native (AI/AN; 4.66), Hispanic white (4.11), Asian/Pacific Islander (A/PI; 1.95), and black (1.20) men. Non-Hispanic white men were more likely to present with smaller tumors (3.5 cm) and localized disease (72.6%) than were men of other races/ethnicities. Between 1992 and 2011, TGCT incidence increased significantly among Hispanic white [annual percent change (APC) = 2.94, p < 0.0001], black (APC = 1.67, p = 0.03), non-Hispanic white (APC = 1.23, p < 0.0001), and A/PI (APC = 1.04, p = 0.05) men. Incidence rates also increased, although not significantly, among AI/AN men (APC = 2.96, p = 0.06). The increases were greater for non-seminoma than seminoma. In summary, while non-Hispanic white men in the US continue to have the highest incidence of TGCT, they present at more favorable stages of disease and with smaller tumors than do other men. The increasing rates among non-white men, in conjunction with the larger proportion of non-localized stage disease, suggest an area where future research is warranted.

International patterns and trends in testicular cancer incidence, overall and by histologic subtype, 1973-2007.

Incidence rates of testicular cancer in Northern European and North American countries have been widely reported, whereas rates in other populations, such as Eastern Europe, Central/South America, Asia, and Africa, have been less frequently evaluated. We examined testicular cancer incidence rates overall and by histologic type by calendar time and birth cohort for selected global populations 1973-2007. Age-standardized incidence rates over succeeding 5-year periods were calculated from volumes 4-9 of Cancer Incidence in Five Continents electronic database (CI5plus) and the newly released CI5X (volume 10) database. Annual percent change over the 35-year period was calculated using weighted least squares regression. Age-period-cohort analyses were performed and observed rates and fitted rate ratios presented by birth cohort. Incidence rates of testicular cancer increased between 1973-1977 and 2003-2007 in most populations evaluated worldwide. Of note, incidence rates in Eastern European countries rose rapidly and approached rates in Northern European countries. Rates in Central and South America also increased and are now intermediate to the high rates among men of European ancestry and low rates among men of Asian or African descent. Some heterogeneity in the trends in seminoma and nonseminoma were observed in Denmark, the United Kingdom, and among US whites, particularly in recent generations, with rapid and uniform increases in the incidence of both histologic types in Slovakia. Reasons for the rising incidence rates among European and American populations remain unexplained; however, changing distributions in the prevalence of risk factors for testicular cancer cannot be ruled out.

Increasing incidence of testicular cancer in the United States and Europe between 1992 and 2009.

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