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
Background & Aims
Cigarette smoking has been implicated in the etiology of esophageal adenocarcinoma, but it is not clear if smoking is a risk factor for Barrett’s esophagus (BE). We investigated whether tobacco smoking and other factors increase risk for BE.
We analyzed data from 5 case-control studies included in the international Barrett’s and Esophageal Adenocarcinoma Consortium. We compared data from subjects with BE (n=1059) with those from subjects with gastroesophageal reflux disease (GERD controls, n=1332) and population-based controls (n=1143), using multivariable logistic regression models to test associations with cigarette smoking. We also tested whether cigarette smoking has synergistic effects with other exposures, which might further increase risk for BE.
Subjects with BE were significantly more likely to have ever-smoked cigarettes than the population-based controls (odds ratio [OR]=1.67; 95% confidence interval [CI], 1.04–2.67) or GERD controls (OR=1.61; 95% CI, 1.33–1.96). Increasing pack-years of smoking increased the risk for BE. There was evidence for a synergy between ever-smoking and heartburn or regurgitation; the attributable proportion of disease among individuals who ever smoked and had heartburn or regurgitation was estimated to be 0.39 (0.25–0.52).
Cigarette smoking is a risk factor for BE. The association strengthened with increased exposure to smoking until ~ 20 pack-years, when it began to plateau. Smoking has synergistic effects with heartburn or regurgitation, indicating that there are various pathways by which tobacco smoking might contribute to the development of BE.
BEACON; esophageal cancer; population study; tobacco
Background & Aims
Regular use of aspirin and other non-steroidal anti-inflammatory drugs (NSAID) has been reported to reduce risks for esophageal adenocarcinoma (EAC) and esophagogastric junctional adenocarcinoma (EGJA). However, individual studies have been too small to accurately assess the effects of medication type, frequency, or duration of use. We performed a pooled analysis to investigate these associations.
We performed a pooled analysis of 6 population-based studies within the Barrett's and Esophageal Adenocarcinoma Consortium to evaluate the association between NSAID use and the risk of EAC and EGJA, using uniform exposure definitions. We collected information from 6 studies (5 case-control and 1 cohort), with a total of 1226 EAC and 1140 EGJA cases, on aspirin and/or NSAID use. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariate adjusted logistic regression models and then pooled using a random effects meta-analysis model.
Compared to non-users, individuals who have used NSAIDs had a statistically significant, reduced risk of EAC (OR=0.68; 95% CI, 0.56–0.82); they also appeared to have a reduced risk of EGJA (OR=0.84; 95% CI, 0.68–1.03). Similar reductions in risk were observed among individuals who took aspirin or non-aspirin NSAIDs. The highest levels of frequency (≥daily) and duration (≥10 years) of NSAID use were associated with an approximately 40% reduction in risk for EAC: OR=0.56 (95% CI, 0.43–0.73; P-trend, <.001) and OR=0.63 (95% CI, 0.45–0.90; P-trend, 0.04), respectively.
Although reverse causation could, in part, explain the inverse association observed between NSAID use and EAC risk, pooled analysis indicates a role for NSAIDs in prevention of adenocarcinomas of the esophagus and esophagogastric junction.
BEACON; Esophageal Neoplasm; Stomach Cancer; Anti-Inflammatory Agent
Background Previous studies suggest an association between obesity and oesophageal (OA) and oesophagogastric junction adenocarcinomas (OGJA). However, these studies have been limited in their ability to assess whether the effects of obesity vary by gender or by the presence of gastro-oesophageal reflux (GERD) symptoms.
Methods Individual participant data from 12 epidemiological studies (8 North American, 3 European and 1 Australian) comprising 1997 OA cases, 1900 OGJA cases and 11 159 control subjects were pooled. Logistic regression was used to estimate study-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between body mass index (BMI, kg/m2) and the risk of OA and OGJA. Random-effects meta-analysis was used to combine these ORs. We also investigated effect modification and synergistic interaction of BMI with GERD symptoms and gender.
Results The association of OA and OGJA increased directly with increasing BMI (P for trend <0.001). Compared with individuals with a BMI <25, BMI ≥40 was associated with both OA (OR 4.76, 95% CI 2.96–7.66) and OGJA (OR 3.07, 95% CI 1.89–4.99). These associations were similar when stratified by gender and GERD symptoms. There was evidence for synergistic interaction between BMI and GERD symptoms in relation to OA/OGJA risk.
Conclusions These data indicate that BMI is directly associated with OA and OGJA risk in both men and women and in those with and without GERD symptoms. Disentangling the relationship between BMI and GERD will be important for understanding preventive efforts for OA and OGJA.
Oesophageal neoplasms; aetiology; risk factors; gastro-oesophageal reflux; obesity; oesophagogastric junction
Cigarette smoking is associated with esophageal adenocarcinoma (EAC), esophagogastric junctional adenocarcinoma (EGJA) and esophageal squamous cell carcinoma (ESCC), and alcohol consumption with ESCC. However, no analyses have examined how delivery rate modifies the strength of odds ratio (OR) trends with total exposure, i.e., the impact on the OR for a fixed total exposure of high exposure rate for short duration compared with low exposure rate for long duration.
The authors pooled data from 12 case-control studies from the Barrett’s Esophagus and Esophageal Adenocarcinoma Consortium (BEACON), including 1,242 (EAC), 1,263 (EGJA) and 954 (ESCC) cases and 7,053 controls, modeled joint ORs for cumulative exposure and exposure rate for cigarette smoking and alcohol consumption, and evaluated effect modification by sex, body mass index (BMI), age and self-reported acid reflux.
For smoking, all sites exhibited inverse delivery rate effects, whereby ORs with pack-years increased, but trends weakened with increasing cigarettes/day. None of the examined factors modified associations, except for ESCC where younger ages at diagnosis enhanced smoking effects (P<0.01). For EAC and EGJA, ORs with drink-years exhibited inverse associations in <5 drinks/day consumers and no association in heavier consumers. For ESCC, ORs with drink-years increased, with trends strengthening with greater drinks/day. There was no significant effect modification, except for EAC and EGJA where acid reflux mitigated the inverse associations (P=0.02). For ESCC, younger ages at diagnosis enhanced drinking-related ORs (P<0.01).
Patterns of ORs by pack-years and drink-years, delivery rate effects and effect modifiers revealed common as well as distinct etiologic elements for these diseases.
alcohol drinking; risk model; smoking
Background and aims
Alcohol intake is a strong and well-established risk factor for esophageal squamous cell carcinoma (ESCC), but the association with esophageal adenocarcinoma (EA) or adjacent tumors of the esophagogastric junction (EGJA), remains unclear. Therefore, we determined the association of alcohol intake with ESCC, EA, and EGJA in nine case-control studies and two cohort studies of the Barrett’s Esophagus and Esophageal Adenocarcinoma Consortium (BEACON).
Materials and methods
We collected information on alcohol intake, age, sex, education, body mass index, gastroesophageal reflux, and tobacco smoking from each study. Along with 10,854 controls, 1,821 EA, and 1,837 EGJA, seven studies also collected ESCC cases (n=1,016). Study-specific odds ratios (OR) and 95% confidence intervals (CI) were calculated from multivariate-adjusted logistic regression models for alcohol intake in categories compared to non-drinkers. Summary risk estimates were obtained by random effects models.
We observed no increase in risk of EA or EGJA for increasing levels of any of the alcohol intake measures examined. ORs for the highest frequency category (≥7 drinks per day) were 0.97 (95% CI = 0.68-1.36) for EA and 0.77 (95% CI = 0.54-1.10) for EGJA. Suggestive findings linked moderate intake (e.g. 0.5 to <1 drinks per day) to decreased risk of EA (OR = 0.63 95% CI = 0.41-0.99) and EGJA (OR = 0.78; 95% CI = 0.62-0.99). In contrast, alcohol intake was strongly associated with increased risk of ESCC (OR for ≥7 drinks per day= 9.62, 95%CI=4.26-21.71).
In contrast to ESCC, higher alcohol consumption was not associated with increased risk of either EA or EGJA. The apparent inverse association observed with moderate alcohol intake should be evaluated in future prospective studies.
Alcohol Drinking; Esophageal Neoplasms; Stomach Neoplasms; 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
In Western countries, the epidemiology of esophageal cancer has changed markedly over the past several decades with squamous cell carcinoma undergoing a rapid decline and adenocarcinoma progressively increasing. Although the prevalence of gastroesophageal reflux is increasing in Asia, the prevalence of Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) have so far remained low in most Asian countries for which data are available. This provides a unique opportunity for research into the initiating factors of BE and EAC. The Asian Barrett’s Consortium recently conducted a review of published studies on BE from Asia to assess the current status of BE research in Asia, and to recommend potential areas for future BE research in the region. Differences in study design, enrolled population, and endoscopic biopsy protocols used have led to substantial variability in the reported BE prevalence (0.06% to 19.9%) across Asia. As has been observed in Western countries, increased age, male sex, tobacco smoking, reflux symptoms, and erosive esophagitis have been found to be risk factors for BE in several case-control studies from Asia. The Prague C and M criteria, developed to provide better interobserver reliability in diagnosis and grading of BE, are currently under extensive evaluation of their applicability in the Asian population. The Asian Barrett’s Consortium believes that only after adequate reliability in endoscopic and histological diagnosis has been demonstrated will Asian clinicians initiate collaborative projects to identify etiologic determinants of BE and its ensuing malignant transformation. At present, data regarding the management and long-term outcome of BE are extremely limited in Asia. More studies of BE in this geographic area are warranted.
Barrett’s esophagus; prevalence; risk factor; gastroesophageal reflux disease; esophageal adenocarcinoma
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
Previous studies that showed an association between smoking and adenocarcinomas of the esophagus and esophagogastric junction were limited in their ability to assess differences by tumor site, sex, dose–response, and duration of cigarette smoking cessation.
We used primary data from 10 population-based case–control studies and two cohort studies from the Barrett’s Esophagus and Esophageal Adenocarcinoma Consortium. Analyses were restricted to white non-Hispanic men and women. Patients were classified as having esophageal adenocarcinoma (n = 1540), esophagogastric junctional adenocarcinoma (n = 1450), or a combination of both (all adenocarcinoma; n = 2990). Control subjects (n = 9453) were population based. Associations between pack-years of cigarette smoking and risks of adenocarcinomas were assessed, as well as their potential modification by sex and duration of smoking cessation. Study-specific odds ratios (ORs) estimated using multivariable logistic regression models, adjusted for age, sex, body mass index, education, and gastroesophageal reflux, were pooled using a meta-analytic methodology to generate summary odds ratios. All statistical tests were two-sided.
The summary odds ratios demonstrated strong associations between cigarette smoking and esophageal adenocarcinoma (OR = 1.96, 95% confidence interval [CI] = 1.64 to 2.34), esophagogastric junctional adenocarcinoma (OR = 2.18, 95% CI = 1.84 to 2.58), and all adenocarcinoma (OR = 2.08, 95% CI = 1.83 to 2.37). In addition, there was a strong dose–response association between pack-years of cigarette smoking and each outcome (P < .001). Compared with current smokers, longer smoking cessation was associated with a decreased risk of all adenocarcinoma after adjusting for pack-years (<10 years of smoking cessation: OR = 0.82, 95% CI = 0.60 to 1.13; and ≥10 years of smoking cessation: OR = 0.71, 95% CI = 0.56 to 0.89). Sex-specific summary odds ratios were similar.
Cigarette smoking is associated with increased risks of adenocarcinomas of the esophagus and esophagogastric junction in white men and women; compared with current smoking, smoking cessation was associated with reduced risks.
Helicobacter pylori (H. pylori) can induce gastric atrophy in humans, which in turn increases gastric cancer risk. Whether H. pylori and gastric atrophy also affect the risk of esophageal squamous cell carcinoma (ESCC), however, remains unresolved.
We performed a nested case-control study within the prospective ATBC Study to assess these relationships. The ATBC Study is composed of 29,133 Finnish male smokers, aged 50–69, who were recruited during 1985–1988. Using baseline sera, we assessed H. pylori status (via IgG antibodies against whole-cell and CagA antigens) and gastric atrophy status (via the biomarkers pepsinogen I (PGI) and II (PGII)) in 79 ESCC cases and 94 controls. Logistic regression with adjustment for age, date of blood draw, education, cigarette smoking, alcohol, body mass index, and fruit and vegetable intake was used to estimate odds ratios (OR) and 95% confidence intervals (95%CI).
Gastric atrophy (PGI:PGII <4) was associated with ESCC (OR=4.58, 95%CI:2.00–10.48). There was no evidence for an association between H. pylori and ESCC (OR=0.94, 95%CI:0.40–2.24).
These results could be explained by misclassification of H. pylori status due to serologic amnesia, ESCC risk being dependent upon the functional consequences or interactions of H. pylori, rather than the infection per se, gastric atrophy having a different histogenesis in ESCC without being primarily dependent upon H. pylori acquisition, or a lack of statistical power to detect an effect.
Validation of these results may warrant mechanistic studies to determine the route of association between gastric atrophy and ESCC.
Atrophy; Esophageal Neoplasms; Helicobacter pylori; Nested Case-Control Studies; Pepsinogens; Prospective Studies
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
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
Globally, testicular cancer incidence is highest among men of northern European ancestry and lowest among men of Asian and African descent. Incidence rates have been increasing around the world for at least 50 years, but mortality rates, at least in developed countries, have been declining. While reasons for the decreases in mortality are related to improvements in therapeutic regimes introduced in the late 1970s, reasons for the increase in incidence are less well understood. An accumulating body of evidence suggests, however, that testicular cancer arises in fetal life. Perinatal factors, including exposure to endocrine disrupting chemicals, have been suggested to be related to risk.
testicular germ cell tumor; seminoma; nonseminoma; perinatal etiology
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.
Methods EMBASE, PubMed, Scopus and Web of Science databases were searched using sensitive search strategies. Meta-analysis was undertaken using STATA 10.
Results A total of 5865 references were retrieved, of which 67 met the inclusion criteria and contributed data to at least one perinatal analysis. Random effects meta-analysis found maternal bleeding during pregnancy [odds ratio (OR) 1.33, 95% confidence interval (CI) 1.02–1.73], birth order (primiparous vs not, 1.08, 95% CI 1.01–1.16; second vs first, OR 0.94, 95% CI 0.88–0.99; third vs first, OR 0.91, 95% CI 0.83–1.01; fourth vs first, OR 0.80, 95% CI 0.69–0.94) and sibship size (2 vs 1, OR 0.93, 95% CI 0.75–1.15; 3 vs 1, OR 0.89, 95% CI 0.74–1.07; 4 vs 1, OR 0.75, 95% CI 0.62–0.90) to be associated with testicular cancer risk. Meta-analyses that produced summary estimates which indicated no association included maternal age, maternal nausea, maternal hypertension, pre-eclampsia, breech delivery and caesarean section. Meta-regression provided evidence that continent of study is important in the relationship between caesarean section and testicular cancer (P = 0.035), and a meta-analysis restricted to the three studies from the USA was suggestive of association (OR 1.67, 95% CI 1.07–2.56).
Conclusions This systematic review and meta-analysis has found evidence for associations of maternal bleeding, birth order, sibship size and possibly caesarean section with risk of testicular cancer.
Epidemiology; meta-analysis; pregnancy; review, systematic; testicular neoplasms
Testicular germ cell tumors (TGCT) are comprised of two histologic groups, seminomas and nonseminomas. We postulated that the possible divergent pathogeneses of these histologies may be partially explained by variable levels of net endogenous DNA damage. To test our hypothesis, we conducted a case-case analysis of 51 seminoma and 61 nonseminoma patients using data and specimens from the Familial Testicular Cancer study and the U.S. Radiologic Technologists cohort. A lymphoblastoid cell line was cultured for each patient and the alkaline comet assay was used to determine four parameters: tail DNA, tail length, comet distributed moment (CDM) and Olive tail moment (OTM). Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated using logistic regression. Values for tail length, tail DNA, CDM and OTM were modeled as categorical variables using the 50th and 75th percentiles of the seminoma group. Tail DNA was significantly associated with nonseminoma compared to seminoma (OR50th percentile=3.31, 95%CI: 1.00, 10.98; OR75th percentile=3.71, 95%CI: 1.04, 13.20; p for trend=0.039). OTM exhibited similar, albeit statistically non-significant, risk estimates (OR50th percentile=2.27, 95%CI: 0.75, 6.87; OR75th percentile=2.40, 95%CI: 0.75, 7.71; p for trend=0.12) whereas tail length and CDM showed no association. In conclusion, the results for tail DNA and OTM indicate that net endogenous levels are higher in patients who develop nonseminoma compared with seminoma. This may partly explain the more aggressive biology and younger age-of-onset of this histologic subgroup compared with the relatively less aggressive, later-onset seminoma.
comet assay; nonseminoma; DNA damage; seminoma; testicular neoplasms
Cancer epidemiology manuscripts often point out that cancer rates tend to be higher among males than females, yet rarely is this theme the subject of investigation.
We used the Surveillance, Epidemiology, and End Results (SEER) program data to compute age-adjusted (2000 US standard population) sex-specific incidence rates and male-to-female incidence rate ratios (IRR) for specific cancer sites and histologies for the period 1975-2004.
The ten cancers with the largest male-to-female IRR were Kaposi sarcoma (28.73), lip (7.16), larynx (5.17), mesothelioma (4.88), hypopharynx (4.13), urinary bladder (3.92), esophagus (3.49), tonsil (3.07), oropharynx (3.06) and other urinary organs (2.92). Only five cancers had a higher incidence in females compared to males: breast (0.01), peritoneum, omentum and mesentery (0.18), thyroid (0.39), gallbladder (0.57), and anus, anal canal and anorectum (0.81). Between 1975 and 2004, the largest consistent increases in male-to-female IRR were for cancers of the tonsil, oropharynx, skin excluding basal and squamous, and esophagus, while the largest consistent decreases in IRR were for cancers of the lip and lung and bronchus. Male-to-female IRRs varied considerably by age, the largest increases of which were for ages 40-59 years for tonsil cancer and hepatocellular carcinoma. The largest decreases in male-to-female IRR by age, meanwhile, were for ages 30-49 years for thyroid cancer, ages ≥70 years for esophageal squamous cell carcinoma, and ages ≥30 years for lung and bronchus cancer.
These observations emphasize the importance of sex in cancer etiopathogenesis and may suggest novel avenues of investigation.
Sex; Male; Female; SEER program; Neoplasms; Incidence; Epidemiology
Assessment of cancer incidence trends within the U.S. have mostly relied upon Surveillance, Epidemiology, and End Results (SEER) data, with implicit inference that such is representative of the general population. However, many cancer policy decisions are based at a more granular level. To help inform such, analyses of regional cancer incidence data are needed. Leveraging the unique resource of National Program of Cancer Registries (NPCR)-SEER, we assessed whether regional rates and trends of esophageal cancer significantly deviated from national estimates.
From NPCR-SEER, we extracted cancer case counts and populations for whites aged 45–84 years by calendar year, histology, sex, and census region for the period 1999–2008. We calculated age-standardized incidence rates (ASRs), annual percent changes (APCs), and male-to-female incidence rate ratios (IRRs).
This analysis included 65,823 esophageal adenocarcinomas and 27,094 esophageal squamous cell carcinomas diagnosed during 778 million person-years. We observed significant geographic variability in incidence rates and trends, especially for esophageal adenocarcinomas in males: ASRs were highest in the Northeast (17.7 per 100,000) and Midwest (18.1). Both were significantly higher than the national estimate (16.0). In addition, the Northeast APC was 62% higher than the national estimate (3.19% vs. 1.97%). Lastly, IRRs remained fairly constant across calendar time, despite changes in incidence rates.
Significant regional variations in esophageal cancer incidence trends exist in the U.S. Stable IRRs may indicate the predominant factors affecting incidence rates are similar in men and women.