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Background: Military and general populations differ in factors related to cancer occurrence and diagnosis. This study compared incidence of colorectal, lung, prostate, testicular, breast, and cervical cancers between the US military and general US populations. Methods: Data from the US Department of Defense's Automated Central Tumor Registry (ACTUR) and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program were analyzed. Persons in ACTUR were active‐duty members 20–59 years old during 1990–013. The same criteria applied to persons in SEER. Age‐adjusted incidence rates, incidence rate ratios, and 95% confidence intervals were calculated by sex, race, age, and cancer stage. Temporal trends were analyzed. Results: ACTUR had higher rates of prostate and breast cancers, particularly in 40‐ to 59‐year‐olds. Further analyses by tumor stage showed this was primarily confined to localized stage. Incidence rates of colorectal, lung, testicular, and cervical cancers were significantly lower in ACTUR than in SEER, primarily for regional and distant tumors in men. Temporal incidence trends were generally similar overall and by stage between the populations, although distant colorectal cancer incidence tended to decrease starting in 2006 in ACTUR whereas it increased during the same period in SEER. Conclusion: Higher rates of breast and prostate cancers in servicemembers 40–59 years of age than in the general population may result from greater cancer screening utilization or cumulative military exposures. Lower incidence of other cancers in servicemembers may be associated with better health status. Incidence rates of local staged prostate and breast cancers were higher in the military than the general population among 40‐ to 59‐year‐olds. Incidence rates of colorectal, lung, and testicular cancers among men were lower in the military than the general population, particularly among 20‐ to 39‐year‐olds. [ABSTRACT FROM AUTHOR]

Background: In the last decades, an increasing incidence of testicular cancer has been observed in several countries worldwide. Although mortality rates have been variable in many countries, little information is available from Latin America and the Caribbean (LAC). Therefore, we examined mortality trends of testicular cancer in the last two decades. Methods: Age-standardized mortality rates (ASMR) of testicular cancer per 100,000 men-years were estimated using the World Health Organization mortality database from 1997 to 2019. We examined the mortality trends and computed annual percent change (APC) for all ages and the following age groups, 15–29, 30–44, 15–44, and ≥ 45 years. Results: Ten countries had mortality rates greater than 0.43 per 100,000 men, with the highest rates for Chile, Mexico, and Argentina. Significant increases in mortality rates were observed in Argentina, Brazil Colombia, and Mexico in all ages, and < 45 years, while Colombia, Ecuador, Mexico, and Peru reported significant downward trends in males aged ≥ 45 years. Only Chile showed significant decreases for all ages and age groups studied. Conclusion: Mortality by testicular cancer increased among LAC countries in males of all ages and across age groups. A reduction in mortality rates was observed only in Chilean males of all ages and in men ≥ 45 years in several countries. Strengthening of early detection among symptomatic males may decrease the mortality by this neoplasm. [ABSTRACT FROM AUTHOR]

With 74 500 new cases worldwide in 2020, testicular cancer ranks as the 20th leading cancer type, but is the most common cancer in young men of European ancestry. While testicular cancer incidence has been rising in many populations, mortality trends, at least those in high‐income settings, have been in decline since the 1970s following the introduction of platinum‐based chemotherapy. To examine current incidence and mortality patterns, we extracted the new cases of, and deaths from cancers of the testis from the GLOBOCAN 2020 database. In 2020, testicular cancer was the most common cancer in men aged 15 to 44 in 62 countries worldwide. Incidence rates were highest in West‐, North‐ and South‐Europe and Oceania (age‐standardised rate, ASR ≥7/100 000), followed by North America (5.6/100 000 and lowest (<2/100 000) in Asia and Africa. The mortality rates were highest in Central and South America (0.84 and 0.54 per 100 000, respectively), followed by Eastern and Southern Europe, and Western and Southern Africa. The lowest mortality rates were in Northern Europe, Northern Africa and Eastern Asia (0.16, 0.14, 0.9 per 100 000, respectively). At the country level, incidence rates varied over 100‐fold, from 10/100 000 in Norway, Slovenia, Denmark and Germany to ≤0.10/100 000 in Gambia, Guinea, Liberia, Lesotho. Mortality rates were highest in Fiji, Argentina and Mexico. Our results indicate a higher mortality burden in countries undergoing economic transitions and reinforce the need for more equitable access to testicular cancer diagnosis and treatment globally. [ABSTRACT FROM AUTHOR]

Testicular cancer is the most common cancer among young men of European ancestry, with about one‐third of all cases occurring in Europe. With the historically increasing trends in some high‐incidence populations reported to have stabilised in recent years, we aimed to assess recent trends and predict the future testicular cancer incidence burden across Europe. We extracted testicular cancer (ICD‐10 C62) incidence data from Cancer Incidence in Five Continents Volumes VII–XI and complemented this with data published by registries from 28 European countries. We predicted cancer incidence rates and the number of incident cases in Europe in the year 2035 using the NORDPRED age‐period‐cohort model. Testicular cancer incidence rates will increase in 21 out of 28 countries over the period 2010–2035, with trends attenuating in the high‐incidence populations of Denmark, Norway, Switzerland and Austria. Although population ageing would be expected to reduce the number of cases, this demographic effect is outweighed by increasing risk, leading to an overall increase in the number of cases by 2035 in Europe, and by region (21, 13 and 32% in Northern, Western and Eastern Europe, respectively). Declines are however predicted in Italy and Spain, amounting to 12% less cases in 2035 in Southern Europe overall. In conclusion, the burden of testicular cancer incidence in Europe will continue to increase, particularly in historically lower‐risk countries. The largest increase in the number of testicular cancer patients is predicted in Eastern Europe, where survival is lower, reinforcing the need to ensure the provision of effective treatment across Europe. What's new? Testicular cancer (TC) is the most common cancer among young men of European ancestry. As the population ages, will rates of TC decrease? In this study, the authors found that, on the contrary, TC risk is predicted to rise in many European countries through the year 2035. The largest increase in the number of TC patients (32%) is predicted in Eastern Europe, where survival is also lower. These results reinforce the need to ensure that effective treatment is provided throughout Europe. [ABSTRACT FROM AUTHOR]

Study Question: Can subphenotype analysis of genome-wide association study (GWAS) data from subjects with testicular germ cell tumor (TGCT) provide insight into cryptorchidism (undescended testis, UDT) susceptibility?Summary Answer: Suggestive intragenic GWAS signals common to UDT, TGCT case-case and TGCT case-control analyses occur in genes encoding RBFOX RNA-binding proteins (RBPs) and their neurodevelopmental targets.What Is Known Already: UDT is a strong risk factor for TGCT, but while genetic risk factors for TGCT are well-known, genetic susceptibility to UDT is poorly understood and appears to be more complex.Study Design, Size, Duration: We performed a secondary subphenotype analysis of existing GWAS data from the Testicular Cancer Consortium (TECAC) and compared these results with our previously published UDT GWAS data, and with data previously acquired from studies of the fetal rat gubernaculum.Participants/materials, Setting, Methods: Studies from the National Cancer Institute (NCI), United Kingdom (UK) and University of Pennsylvania (Penn) that enrolled white subjects were the source of the TGCT GWAS data. We completed UDT subphenotype case-case (TGCT/UDT vs TGCT/non-UDT) and case-control (TGCT/UDT vs control), collectively referred to as 'TECAC' analyses, followed by a meta-analysis comprising 129 TGCT/UDT cases, 1771 TGCT/non-UDT cases, and 3967 unaffected controls. We reanalyzed our UDT GWAS results comprising 844 cases and 2718 controls by mapping suggestive UDT and TECAC signals (defined as P < 0.001) to genes using Ingenuity Pathway Analysis (IPA®). We compared associated pathways and enriched gene categories common to all analyses after Benjamini-Hochberg multiple testing correction, and analyzed transcript levels and protein expression using qRT-PCR and rat fetal gubernaculum confocal imaging, respectively.Main Results and the Role Of Chance: We found suggestive signals within 19 genes common to all three analyses, including RBFOX1 and RBFOX3, neurodevelopmental paralogs that encode RBPs targeting (U)GCATG-containing transcripts. Ten of the 19 genes participate in neurodevelopment and/or contribute to risk of neurodevelopmental disorders. Experimentally predicted RBFOX gene targets were strongly overrepresented among suggestive intragenic signals for the UDT (117 of 628 (19%), P = 3.5 × 10-24), TECAC case-case (129 of 711 (18%), P = 2.5 × 10-27) and TECAC case-control (117 of 679 (17%), P = 2 × 10-21) analyses, and a majority of the genes common to all three analyses (12 of 19 (63%), P = 3 × 10-9) are predicted RBFOX targets. Rbfox1, Rbfox2 and their encoded proteins are expressed in the rat fetal gubernaculum. Predicted RBFOX targets are also enriched among transcripts differentially regulated in the fetal gubernaculum during normal development (P = 3 × 10-31), in response to in vitro hormonal stimulation (P = 5 × 10-45) and in the cryptorchid LE/orl rat (P = 2 × 10-42).Large Scale Data: GWAS data included in this study are available in the database of Genotypes and Phenotypes (dbGaP accession numbers phs000986.v1.p1 and phs001349.v1p1).Limitations, Reasons For Caution: These GWAS data did not reach genome-wide significance for any individual analysis. UDT appears to have a complex etiology that also includes environmental factors, and such complexity may require much larger sample sizes than are currently available. The current methodology may also introduce bias that favors false discovery of larger genes.Wider Implications Of the Findings: Common suggestive intragenic GWAS signals suggest that RBFOX paralogs and other neurodevelopmental genes are potential UDT risk candidates, and potential TGCT susceptibility modifiers. Enrichment of predicted RBFOX targets among differentially expressed transcripts in the fetal gubernaculum additionally suggests a role for this RBP family in regulation of testicular descent. As RBFOX proteins regulate alternative splicing of Calca to generate calcitonin gene-related peptide, a protein linked to development and function of the gubernaculum, additional studies that address the role of these proteins in UDT are warranted.Study Funding/competing Interest(s): The Eunice Kennedy Shriver National Institute for Child Health and Human Development (R01HD060769); National Center for Research Resources (P20RR20173), National Institute of General Medical Sciences (P20GM103464), Nemours Biomedical Research, the Testicular Cancer Consortium (U01CA164947), the Intramural Research Program of the NCI, a support services contract HHSN26120130003C with IMS, Inc., the Abramson Cancer Center at Penn, National Cancer Institute (CA114478), the Institute of Cancer Research, UK and the Wellcome Trust Case-Control Consortium (WTCCC) 2. None of the authors reports a conflict of interest. [ABSTRACT FROM AUTHOR]

Background: Testicular germ cell tumors (TGCTs) are rare tumors in the general population but are the most commonly occurring malignancy among males between ages 15 and 44 years in the United States (US). Although non-Hispanic whites (NHWs) have the highest incidence in the US, rates among Hispanics have increased the most in recent years. To forecast what these incidence rates may be in the future, an analysis of TGCT incidence in the Surveillance, Epidemiology, and End Results program and the National Program of Cancer Registries was conducted.Methods: TGCT incidence data among males ages 15 to 59 years for the years 1999 to 2012 were obtained from 39 US cancer registries. Incidence rates through 2026 were forecast using age-period-cohort models stratified by race/ethnicity, histology (seminoma, nonseminoma), and age.Results: Between 1999 and 2012, TGCT incidence rates, both overall and by histology, were highest among NHWs, followed by Hispanics, Asian/Pacific Islanders, and non-Hispanic blacks. Between 2013 and 2026, rates among Hispanics were forecast to increase annually by 3.96% (95% confidence interval, 3.88%-4.03%), resulting in the highest rate of increase of any racial/ethnic group. By 2026, the highest TGCT rates in the US will be among Hispanics because of increases in both seminomas and nonseminomas. Rates among NHWs will slightly increase, whereas rates among other groups will slightly decrease.Conclusions: By 2026, Hispanics will have the highest rate of TGCT of any racial/ethnic group in the US because of the rising incidence among recent birth cohorts. Reasons for the increase in younger Hispanics merit further exploration. Cancer 2017;123:2320-2328. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Germline inactivating mutations of isoform 4 of phosphodiesterase (PDE) 11A (coded by the PDE11A gene) have been associated with familial adrenocortical tumors and familial testicular cancer. Testicular tissue is unique in expressing all four isoforms of PDE11A. In a prior candidate gene study of 94 familial testicular germ cell tumor (TGCT) subjects, we identified a significant association between the presence of functionally abnormal variants in PDE11A and familial TGCT risk. To validate this novel observation, we sequenced the PDE11A coding region in 259 additional TGCT patients (both familial and sporadic) and 363 controls. We identified 55 PDE11A variants: 20 missense, four splice-site, two nonsense, seven synonymous, and 22 intronic. Ten missense variants were novel; nine occurred in transcript variant 4 and one in transcript variant 3. Five rare mutations (p.F258Y, p.G291R, p.V820M, p.R545X, and p.K568R) were present only in cases and were significantly more common in cases vs controls (PZ0.0037). The latter two novel variants were functionally characterized and shown to be functionally inactivating, resulting in reduced PDE activity and increased cAMP levels. In further analysis of this cohort, we focused on white participants only to minimize confounding due to population stratification. This study builds upon our prior reports implicating PDE11A variants in familial TGCT, provides the first independent validation of those findings, extends that work to sporadic testicular cancer, demonstrates that these variants are uncommonly but reproducibly associated with TGCT, and refines our understanding regarding which specific inactivating PDE11A variants are most likely to be associated with TGCT risk. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Objective: 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. Methods: 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. Results: 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. Conclusion: 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. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

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 mother. [ABSTRACT FROM PUBLISHER]

The incidence of testicular germ cell tumours (TGCT) has increased in white and black men in the United States. Little is known, however, about trends among men of other racial/ethnic groups. The current study sought to examine TGCT patterns among men of Asian/Pacific Islander/American Indian/ Alaska Native (API/AIAN) and Hispanic ancestries and to determine whether tumours in these groups are diagnosed at comparable stages and sizes to tumours in white and black men. TGCT incidence data and tumour characteristics were drawn from the Surveillance, Epidemiology and End Results registries for two time periods: 1973–2003 and 1992–2003. In 1973–2003, TGCT rates were significantly lower among black (rate ratio = 0.18, p < 0.001) and API/AIAN (rate ratio = 0.37, p < 0.001) men than among white men. Among white and API/AIAN men, rates increased over 60%, mainly prior to 1989–1993. Among black men, rates increased almost 40%, mainly after 1989–1993. Among white and API/AIAN men, increasing proportions of localized disease were diagnosed over time, while the opposite trend was seen among black men. In 1992–2003, TGCT incidence among Hispanic white men (3.46/100 000) was significantly lower than it was among non-Hispanic white men, but rates of both seminoma and non-seminoma increased. While the incidence of TGCT increased among all men, different patterns in the increase were evident. These data suggest that rates are increasing among Hispanic white men and black men, but are stabilizing among white men and API/AIAN men. The peak of the TGCT epidemic may have been reached in these latter groups. [ABSTRACT FROM AUTHOR]

Background Although modern treatments for testicular cancer are associated with increased survival, the long-term health effects of these treatments are unclear. We conducted a population-based study to quantify the long-term risks of mortality from noncancer causes among men with testicular cancer. Methods We identified 38907 one-year survivors of testicular cancer within 14 population-based cancer registries in North America and Europe (from 1943 through 2002). We used data from these registries to calculate standardized mortality ratios (SMRs) for noncancer deaths and to evaluate associations between histology, age at testicular cancer diagnosis, calendar year of diagnosis, and initial treatment and the risk of noncancer mortality. All statistical tests were two-sided. Results A total of 2942 deaths from all noncancer causes were reported after a median follow-up of 10 years, exceeding the expected number of deaths from all noncancer causes in the general population by 6% (SMR = 1.06, 95% confidence interval [CI] = 1.02 to 1.10); the noncancer standardized mortality ratios did not differ statistically significantly between patients diagnosed before and after 1975, when cisplatin-based chemotherapy came into widespread use. Compared with the general population, testicular cancer survivors had higher mortality from infections (SMR = 1.28, 95% CI = 1.12 to 1.47) and from digestive diseases (SMR = 1.44, 95% CI = 1.26 to 1.64). Mortality from all circulatory diseases was statistically significantly elevated in men diagnosed with testicular cancer before age 35 years (1.23, 95% CI = 1.09 to 1.39) but not in men diagnosed at older ages (SMR = 0.94; 95% CI = 0.89 to 1.00). Men treated with chemotherapy (with or without radiotherapy) in 1975 or later had higher mortality from all noncancer causes (SMR = 1.34, 95% CI = 1.15 to 1.55), all circulatory diseases (SMR = 1.58, 95% CI = 1.25 to 2.01), all infections (SMR = 2.48, 95% CI = 1.70 to 3.50), and all respiratory diseases (SMR = 2.53, 95% CI = 1.26 to 4.53). Testicular cancer patients who were younger than 35 years at diagnosis and were treated with radiotherapy alone in 1975 or later had higher mortality from all circulatory diseases (SMR = 1.70, 95% CI = 1.21 to 2.31) compared with the general population. Conclusion Men who have survived for at least 1 year after being diagnosed with testicular cancer have a slightly higher risk of dying from noncancer causes, including infections, digestive diseases, and circulatory diseases, than the general population. Men treated with chemotherapy in 1975 or later may be at particularly high risk. [ABSTRACT FROM AUTHOR]

Background: Although risk estimates for synchronous and metachronous contralateral testicular cancers vary widely, many clinicians recommend routine biopsy of the contralateral testis for patients diagnosed with unilateral testicular cancer. We evaluated the risk of contralateral testicular cancer and survival in a large population-based cohort of men diagnosed with testicular cancer before age 55 years. Methods: For 29515 testicular cancer cases reported to the National Cancer Institute's Surveillance, Epidemiology and End Results Program from 1973 through 2001, we estimated the prevalence of synchronous contralateral testicular cancer, the observed-to-expected ratio (O/E) and 15-year cumulative risk of metachronous contralateral testicular cancer, and the 10-year overall survival rate of both synchronous and metachronous contralateral testicular cancer, using the Kaplan- Meier method for the two latter assessments. Age-adjusted multivariable analyses were used to examine risk according to histologic type of the original cancer. Results: A total of 175 men presented with synchronous contralateral testicular cancer; 287 men developed metachronous contralateral testicular cancer (O/E = 12.4 195% confidence interval {CI} = 11.0 to 13.91; 15-year cumulative risk = 1.9% [95% CI = 1.7% to 2.1%]). In the multivariable analysis, only nonseminomatous histology of the first testicular cancer was associated with a statistically significantly decreased risk of metachronous contralateral testicular cancer (hazard ratio [HR] =0.60,95% confidence interval [CI] = 0.46 to 0.79; P < .001). Increasing age at first testicular cancer diagnosis was associated with decreasing risk of nonseminomatous metachronous contralateral testicular cancer (odds ratio = 0.90, 95% CI = 0.86 to 0.94). The 10-year overall survival rate after metachronous contralateral testicular cancer diagnosis was 93% (95% CI = 88% to 96%), and that after synchronous contralateral testicular cancer was 85% (95% CI = 78% to 90%). Conclusions: The low cumulative risk of metachronous contralateral testicular cancer and favorable overall survival of patients diagnosed with metachronous contralateral testicular cancer is in accordance with the current U.S. approach of not performing a biopsy on the contralateral testis. [ABSTRACT FROM AUTHOR]

Discusses the increase in testicular cancer in young men in the United States. Age group that is more likely to develop the disease; Populations that show the highest rate of testicular cancer; Role of germ cell tumors (GCT); Factors that are related to the risk of developing GCT; Importance of studying specific ethnicities and immigrants having GCT; Challenges in testicular cancer epidemiology.

Incidence rates of testicular cancer (TC) have been increasing in many countries since, at least, the mid-20th century without clear explanation. Examining the varying trends across countries and time provides clues to understanding the causes of TC. We have presented incidence data from 41 countries and evaluated incidence trends for the 35-yr period from 1978 to 2012. Cancer registry data from Cancer Incidence in Five Continents (CI5) volumes V–XI, CI5plus, and the NORDCAN database were analysed. Age-standardised rates of TC overall and by histological type were calculated. A joinpoint regression model of the natural log-transformed rates was used to calculate the average annual percent change (AAPC) in incidence. Age-period-cohort modelling was used to examine the effect of birth cohort on rates. While the highest incidence of TC remains in Northern Europe, the gap is closing between higher- and lower-incidence regions. Age-period-cohort modelling found flattening of risk among recent cohorts in Denmark and the UK, a steady increase in risk in the USA (particularly for seminomas), and an increase in risk among more recent cohorts in Costa Rica, Croatia, and Slovakia. The gap between low- and high-incidence countries is closing due to increases in the former and stabilisation in the latter. Understanding the causes of these and other differences in incidence rates between, and within, countries may help further our understanding of the aetiology of this cancer. We examined the rates of testicular cancer in different countries over time. These rates have been increasing, although the rates in high-incidence countries seem to be slowing down, while rates in low-incidence countries are catching up. These trends might help us understand what is causing testicular cancer in general. Rates of testicular cancer are stabilising in high-incidence countries, but rapidly increasing in low-incidence countries. Understanding why this gap is closing, and why differences in rates exist between and within countries, could further our understanding of what causes this cancer. [ABSTRACT FROM AUTHOR]

Background The etiology of testicular germ cell tumors (TGCT) is poorly understood, however, exposure to endocrine disrupting chemicals (EDCs) may be related to increased risk. Personal care products, some of which contain EDCs, are widely used on a daily basis and are known to cross the placenta, be present in breastmilk, and are capable of inducing reproductive tract abnormalities. To determine the association between personal care product use during pregnancy and breastfeeding and TGCT risk, an analysis among mothers of TGCT cases and controls was conducted. Methods The US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) study enrolled TGCT cases and controls and their mothers between 2002 and 2005. The current analysis examined personal care product use during pregnancy among 527 mothers of TGCT cases and 562 mothers of controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression adjusting for identified covariates. Results Maternal use of face lotion more than one time per week was associated with a significantly increased risk of TGCT (OR: 1.42, 95% CI: 1.08–1.86, p-trend: 0.01). None of the other products examined (perfume, hairspray, nail polish, hair dye, permanent wave, body lotion, deodorant, sunscreen) were associated with TGCT risk. Conclusions Frequent exposure to face lotion during pregnancy and while breastfeeding may be associated with increased TGCT risk. Further investigation into the endocrine disrupting effects of personal care products is warranted. [ABSTRACT FROM AUTHOR]

Abstract: Background: Research on early life exposures and testicular germ cell tumors (TGCT) risk has focused on a possible perinatal etiology with a well-known hypothesis suggesting that hormonal involvement during fetal life is associated with risk. Second-to-fourth digit ratio (2D:4D) and left-hand dominance have been proposed as markers of prenatal hormone exposure. Aim: To evaluate associations between 2D:4D digit ratio, right minus left 2D:4D (ΔR−L), and left-hand dominance and TGCT in the U.S. Servicemen's Testicular Tumor Environmental and Endocrine Determinants Study. Methods: A total of 246 TGCT cases and 236 non-testicular cancer controls participated in the current study, and completed a self-administered questionnaire. Associations between digit ratio, hand dominance and TGCT were estimated using unconditional logistic regression adjusting for identified covariates. Results: Right 2D:4D was not associated with TGCT [odds ratio (OR) for a one-standard deviation (SD) increase in right-hand 2D:4D: 1.12, 95% confidence interval (CI): 0.93–1.34]. The results were consistent when evaluating the association based on the left hand. The difference between right and left-hand 2D:4D was also not associated with TGCT risk [OR for a one-SD increase in ΔR−L: 1.03, 95% CI: 0.87–1.23]. Compared to men who reported right-hand dominance, ambidexterity [OR (95% CI)=0.65 (0.30–1.41)] and left-hand dominance [OR (95% CI)=0.79 (0.44–1.44)] were not associated with risk. Conclusions: These results do not support the hypothesis that prenatal hormonal imbalance is associated with TGCT risk. Given the limited sample size, further evaluation of the relationship between TGCT and prenatal hormonal factors using digit ratio, ΔR−L, or left-hand dominance and larger sample size are warranted. [Copyright &y& Elsevier]

Background: The incidence of testicular germ cell tumors (TGCT) is increasing steadily in the United States, particularly among Latinos. TGCT is thought to be initiated in utero and exposure to endocrine-disrupting chemicals, suspected contributors to TGCT pathogenesis, during this critical developmental period may contribute to the rise.Objectives: To assess the relationship between fetal exposure to agricultural endocrine-disrupting pesticides (EDPs) and TGCT risk among adolescents in a diverse population in California.Methods: We conducted a registry-based case-control study of TGCT. Cases, diagnosed between 1997 and 2011, were 15-19 years of age (n = 381). Controls were matched on birth year and race/ethnicity (n = 762). Quantities (kilograms) of 33 pesticides applied within 3 km and 1 km radii of each individual's address before birth were estimated using the Pesticide Use Reporting database. Odds ratios (OR), 95% confidence intervals (CI), and population attributable risk (PAR) were calculated for each EDP (using log-2 transformed values). Risk models considered race/ethnicity, birth year, and neighborhood socioeconomic status.Results: A doubling of nearby acephate applications (3 km and 1 km radii) and malathion applications (1 km radius) was associated with increased risks of TGCT among Latinos only (OR = 1.09; 95% CI:1.01-1.17; 1.30; 95% CI:1.08-1.57, and 1.19; 95% CI:1.01-1.39, respectively), whereas application of carbaryl within a 3 km radius increased TGCT risk in non-Latinos only (OR = 1.14, 95% CI:1.01-1.28). We estimate that acephate was associated with approximately 10% of the TGCT PAR, malathion with 3% and carbaryl with 1%.Conclusions: TGCT among adolescents in California was associated with prenatal residential proximity to acephate and malathion among Latinos, and with carbaryl among non-Latinos. These results suggest that the rise in TGCT risk among Latinos may be associated with exposure to these pesticides. [ABSTRACT FROM AUTHOR]

Purpose: It was hypothesized that the risk for testicular germ cell tumors (TGCTs) is associated with maternal hormone levels. To examine the hypothesis, some studies 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. Methods: Maternal estradiol, estriol, and testosterone levels in first- and third-trimester serum samples were correlated with perinatal factors in 300 mothers representative of populations at high (white Americans) or low (black Americans) risk for TGCT. Results: For white participants, testosterone levels were associated negatively with maternal height (p < 0.01) and age (p = 0.02) and positively with maternal weight (p = 0.02) and body mass index (BMI; p < 0.01), whereas estradiol levels were associated negatively with height (p = 0.03) and positively with son''s birth weight (p = 0.04). For black participants, estriol levels were associated negatively with maternal weight (p = 0.01), BMI (p = 0.02), and gestational age p < 0.01) and positively with son''s birth weight (p < 0.01), length (p = 0.04), and head circumference (p = 0.03). Conclusions: These findings indicate that use of perinatal characteristics as surrogates for hormone levels should be limited to a specific ethnic group. For white men, previously reported associations of TGCT with maternal weight and age may be caused by lower maternal testosterone levels. [Copyright &y& Elsevier]