Subtypes Of Men Research Articles

Diabetes and the risk of bladder cancer subtypes in men and women: results from the Netherlands Cohort Study

Meta-analyses have shown modest positive associations between diabetes mellitus (DM) and bladder cancer risk, but results are heterogeneous. This might be due to lack of distinction between bladder cancer subtypes, between sexes, and possibly between Type 2 and Type 1 DM (T2DM and T1DM). The relationship of T2DM (and secondarily T1DM) characteristics with risk of bladder cancer subtypes (invasive versus noninvasive) was investigated in the Netherlands Cohort Study. In 1986, 120,852 men and women aged 55–69 years provided information on DM and lifestyle data. After 20.3 years of follow-up, multivariable case-cohort analyses were based on 1020 invasive and 1088 noninvasive bladder cancer cases, and 4267 subcohort members with complete data on DM and confounders. While T2DM was not associated with noninvasive bladder cancer, it was statistically significantly associated with invasive bladder cancer risk: the multivariable-adjusted was HR = 1.57 (95% CI 1.04–2.37), comparing participants with T2DM versus without DM. The association was only significant in women, and women showed a stronger association [HR = 2.19 (95% CI 1.10–4.34)] between T2DM and invasive bladder cancer than men [HR = 1.42 (95% CI 0.88–2.30)]; interaction by sex was nonsignificant. Associations were stronger positive in those whose age at diagnosis of T2DM was 55+ years, and in those diagnosed with T2DM less than five years before baseline. T2DM participants using antidiabetic medication had higher invasive bladder cancer risk than those without DM. Exploratory age-sex-adjusted analyses suggested a positive association between T1DM and invasive bladder cancer, but this was based on few cases. These findings suggest that T2DM and possibly T1DM are positively associated with invasive bladder cancer risk.

Prevalence of urinary incontinence in middle-aged and elderly adults in 10 areas in China

Objective: To describe the population and area distribution differences in the prevalence of urinary incontinence in middle-aged and elderly adults in 10 areas in China. Methods: A total of 24 913 participants aged 45-95 years who completed the third resurvey of China Kadoorie Biobank during 2020-2021 were included. The prevalence of urinary incontinence was assessed by an interviewer-administered questionnaire, and urinary incontinence was classified as only stress urinary incontinence, only urgency urinary incontinence and mixed urinary incontinence. The prevalence of urinary incontinence and its subtypes were reported by sex, age and area, and the severity of urinary incontinence and treatment were described. Results: The average age of the participants was (65.4±9.1) years. According to the seventh national census data in 2020, the age-standardized prevalence rates of urinary incontinence was 25.4% in women and 7.0% in men. The age-standardized prevalence rates of only stress, only urgency and mixed incontinence were 1.7%, 4.2% and 1.2% in men and 13.5%, 5.8% and 6.1% in women, respectively. The prevalence rates of urinary incontinence and all subtypes in men and the prevalence of urinary incontinence and all subtypes except only stress urinary incontinence in women all increased with age (P<0.001). After adjusting for age, the prevalence of urinary incontinence in both men and women were higher in rural area than in urban area (P<0.001). The treatment rates in men and women with urinary incontinence were 15.4% and 8.5%, respectively. Conclusions: The prevalence of urinary incontinence was high in middle-aged and elderly adults in China, and the prevalence rate was higher in women than in men, but the treatment rate of urinary incontinence was low.

Abstract PS7-79: Clinicopathological characteristics of male breast cancer in Japan from the national clinical database

Abstract Background: Male breast cancer is a rare cancer. According to the Japanese Breast Cancer Society's Breast Cancer Registry, there were 613 cases of male breast cancer in 2016. It is only 0.6% of all cases of breast cancer incidence. Because of its rarity, there have been no comprehensive studies on characteristics of male breast cancer in Japan. Therefore, there has been few specific treatments developed for male breast cancer. In this study, we investigated the prevalence and clinicopathological characteristics of male breast cancer in Japan, using the most reliable domestic data, the National Clinical Database (NCD). NCD is a database that collects medical information on diseases, treatments, and surgeries in Japan. In collaboration and cooperation with academic societies and academic organizations, NCD maintain and manage the collected data. The data are used in domestic research to evaluate the standards of medical care and support clinical research. This study conducted with a collaboration with NCD and the registration committee of Japan Breast Cancer Society. Materials and Methods: Clinicopathological data were collected from all breast cancer patients in NCD between 2012 and 2018. We compared the male and female breast cancer patients on age, stage, surgical technique, estrogen receptor (ER) status, progesterone receptor (PgR) status, HER2 expression, family history, comorbidities, and systemic treatment history. Results: 3,780 male and 590,636 female breast cancers were enrolled in the study. The median age was 71 years for men (56-87 years, 5-95 percentile) and 61 years for women (40-83 years). The clinical stage in males was 7.2% in stage 0, 36.3% in stage I, 33.4% in stage II, 12.4% in stage III, 1.4% in Stage IV and 4.5% in unknown, respectively. In females, 13.0%, 41.6%, 31.4%, 6.6%, 1.3% and 2.3%, respectively. Breast conserving surgery (BCS) was performed for 14.6% in men 46.2% in women. BCS rate in men is more frequent in Japan compared to in western countries (Ann Oncol. 2018 Feb 1;29(2):405-417). Hormone receptor-positive (HR+; ER+ and/or PgR+) HER2-negative (HER2-) was 88%, HR+HER2-positive (HER2+) was 8%, HR-HER2+ was 1% and HR-HER2- was 3% in men. 74%, 10%, 6% and 10% in women, respectively. The distribution of subtypes in men is similar to western countries. Comorbidity was reported in 42.3% of men and 66.8% of women. Hypertension, diabetes, cardiac disorder and cerebrovascular disorder were more common in men. Conclusion: Male breast cancer is 0.6% of all breast cancer in Japan. Stage III and HR+ is more frequent in male and its tendency is similar to data from western countries. BCS is underwent more frequent in Japan than in western countries. Citation Format: Akihiko Shimomura, Masayuki Nagahashi, Hiraku Kumamaru, Yutaka Yamamoto, Hiromitsu Jinno, Shigeru Imoto, Registration Committee of Japan Breast Cancer Society. Clinicopathological characteristics of male breast cancer in Japan from the national clinical database [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-79.

Cumulative alcohol consumption and stroke risk in men.

Views on the relationship between alcohol consumption and stroke risk remain controversial. Moreover, data on cumulative alcohol intake are limited. We examined the potential impact of cumulative alcohol consumption on the risk of total stroke and its subtypes in men. This prospective study included 23,433 men from the Kailuan Study. Cumulative alcohol consumption was taken as the primary exposure by calculating self-reported alcohol consumption from three consecutive examinations (in 2006, 2008, and 2010). The first occurrence of stroke was confirmed by reviewing medical records from 2010 to 2016. We used Cox proportional hazards regression to analyze the data. During the 5.9 ± 0.8years of follow-up, 678 total strokes were identified, including 595 ischemic stroke (IS), 90 intracerebral hemorrhage and 19 subarachnoid hemorrhage cases. The adjusted hazard ratios (95% confidence intervals) of total stroke for light, moderate and heavy cumulative alcohol consumption were 1.23 (1.01-1.51), 1.49 (1.13-1.97), and 1.50 (1.21-1.86), respectively, compared with those of nondrinkers. The results were similar for IS. Cumulative alcohol consumption was not associated with intracerebral hemorrhage risk (hazard ratio 1.46; 95% confidence interval, 0.74-2.08). Cumulative alcohol consumption is an independent risk factor of total stroke and IS in men in a community-based cohort. Even light alcohol intake increases the risk of total stroke and IS.

Do cancer registries play a role in determining the incidence of non-melanoma skin cancers?

Non-melanoma skin cancers have the highest incidence of all malignancies worldwide. However, cancer registries rarely include data on non-melanoma skin cancers because they tend to be under-reported. To determine incidence rates and changes over time for non-melanoma skin cancers in a mid-sized Brazilian population. We calculated age-standardized rates, adjusted to the world population using the direct method, from 1996-2012 in the Aracaju Cancer Registry and then calculated incidence trends using the Joinpoint Regression Program. We analysed 11,476 cases (5,695 men and 5,781 women) of non-melanoma skin cancer collected during the study period. The histological subtypes in men were 84.5% basal cell carcinoma, 14.5% squamous cell carcinoma, and 1% other histological subtypes, whereas the corresponding percentages in women were 89.1%, 10%, and 0.9%, respectively. Average incidence age-standardized rates were 228.6 (95%CI: 221.6; 235.6) per 100,000 men and 145.4 (95%CI: 141.0; 149.9) per 100,000 women. The incidence mostly increased in the first years for the series and then stabilized. The under-reporting of non-melanoma skin cancers, due to removal of lesions without histopathological confirmation, decisions to keep skin lesions under observation instead of excising them, and deferring medical examination, is a potential pitfall of this study. Age-standardized incidence of non-melanoma skin cancer was high during the study period, but tended to stabilise in the latter years of the study.

Abstract C72: Improving the accuracy and diagnostic power of prostate biopsy for African American patients: The Birmingham Alabama Prostate Cancer (BAPrCa) Consortium

Abstract Study Purpose: Both incidence and mortality data show that the burden of prostate cancer (PrCa) is greater in African Americans (AA) than in European Americans (EA). Socioeconomic factors contribute to this health disparity, but do not fully account for observations that AA are more likely than others to be diagnosed with more aggressive and life threatening forms of PrCa. Prostate biopsies usually establish the diagnosis of PrCa and are used to estimate the extent of the disease (based on the number and location of cores with cancer and involvement of individual cores) and its potential aggressiveness (based on Gleason scores). Health policy groups recommend that men with limited low grade prostate cancer be managed by active surveillance (AS) rather than immediate surgical or radiation treatment. However, the standard-of-care prostate biopsy is limited by sampling error and the possibility that a high grade PrCa might have been missed is a significant concern for many patients who are considering AS; this concern is heightened for AA because of their higher risk of aggressive disease. Moreover, AA are more likely to be diagnosed with high grade/high stage prostate cancer that is not treated surgically and thus not well represented in molecular studies that utilize radical prostatectomy specimens. Our research team established the Birmingham Alabama Prostate Cancer (BAPrCa) Consortium with a major focus on the molecular analysis of prostate biopsies in order to increase the clinically actionable information that can be obtained from these specimens. We use an ancestry-informed approach that is specifically designed to improve the accuracy and diagnostic power of prostate biopsy for AA patients. Experimental Procedures: The BAPrCa Consortium implemented an innovative prostate biopsy “tissue print” technology that permits collection of snap-frozen nitrocellulose blots of biopsy cores without diagnostically compromising these specimens. Tissue prints provide high quality RNA and DNA from biopsies from the full range of patients, including AAs whose cancer is too advanced at diagnosis for radical prostatectomy; this permits the molecular characterization of PrCa subtypes in men diagnosed with high volume/high grade disease who have not been adequately represented in previous molecular profiling studies. Our BAPrCa research protocols include informed consent for genetic ancestry admixture studies. Gene expression analysis of prostate biopsy tissue prints is correlated with histopathology and multiparametric prostate MRI. Results: Our data suggest that in the Birmingham area, higher prostate cancer risk in AA is associated with increasing proportion of West African (WA) ancestry, which may reflect the prevalence of population-specific genetic mutations or variations that contribute to the development of more aggressive disease. As a group, the men diagnosed with high grade PrCa showed a significantly higher level of WA ancestry than the men diagnosed with no cancer (P = 0.001). A similar pattern is observed in comparisons of AA men diagnosed with high grade cancer vs low grade PrCa. Inasmuch as our AIMs genotyping panel uses a small number of well-established AIMS markers, our observation of significantly increased risk of PrCa in AA men with high %WA AIMS ancestry may, if confirmed, have immediate potential clinical applications for improving prostate cancer screening and active surveillance. Moreover, gene expression profiles of biopsies from BAPrCa patients diagnosed with high volume/high grade PrCa revealed two subtypes of high grade PrCa with striking differences in the pathways that drive a shift in tumor fatty acid metabolism; one is a fatty acid synthase (FASN) dominant phenotype and the other a previously unrecognized fatty acid binding protein (FABP5) dominant phenotype. Our data suggest that the FABP5 dominant PrCa subtype is more common in AA and the FASN dominant subtype more common in EA. These findings may provide the basis for more effective dietary interventions and targeted therapies for AA and EA patients with high grade PrCa. Conclusions: By utilizing innovative tissue print techniques for the molecular analyses of prostate biopsies and using an ancestry informed approach in our study designs, the Birmingham Alabama Prostate Cancer (BAPrCa) Consortium has identified new and potentially actionable PrCa signatures that may improve the accuracy and diagnostic power of prostate biopsy for AA patients. Citation Format: Sandra M. Gaston, Soroush Rais-Bahrami, Rick Kittles, Kerry Dehimer, Dennis Otali, Jeffrey W. Nix, Peter N. Kolettis, George Adams, William E. Grizzle. Improving the accuracy and diagnostic power of prostate biopsy for African American patients: The Birmingham Alabama Prostate Cancer (BAPrCa) Consortium. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C72.

Serum testosterone levels and symptom-based depression subtypes in men.

The main objective of this preliminary study was to further clarify the association between testosterone (T) levels and depression by investigating symptom-based depression subtypes in a sample of 64 men. The data were taken from the ZInEP epidemiology survey. Gonadal hormones of a melancholic (n = 25) and an atypical (n = 14) depression subtype, derived from latent class analysis, were compared with those of healthy controls (n = 18). Serum T was assayed using an enzyme-linked immunosorbent assay procedure. Analysis of variance, analysis of covariance, non-parametrical tests, and generalized linear regression models were performed to examine group differences. The atypical depressive subtype showed significantly lower T levels compared with the melancholic depressives. While accumulative evidence indicates that, beyond psychosocial characteristics, the melancholic and atypical depressive subtypes are also distinguishable by biological correlates, the current study expanded this knowledge to include gonadal hormones. Further longitudinal research is warranted to disclose causality by linking the multiple processes in pathogenesis of depression.

Occupational extremely low-frequency magnetic field exposure and selected cancer outcomes in a prospective Dutch cohort

To investigate the association between exposure to occupational extremely low-frequency magnetic fields (ELF-MF) and the risk of a priori selected cancer outcomes within the prospective Netherlands Cohort Study. 120,852 men and women aged 55-69 years at time of enrollment in 1986 were followed up (17.3 years) for incident lung, breast and brain cancer, and hemato-lymphoproliferative malignancies. Information on occupational history and potential confounders such as sex, age, smoking, alcohol use, and attained educational level were collected at baseline through a self-administered questionnaire. Occupational ELF-MF exposure was assigned with a job-exposure matrix. Using a case-cohort approach, associations with cancer incidence were analyzed with Cox regression stratified by sex, using three exposure metrics: (1) ever had a job with low or high exposure to ELF-MF versus background, (2) duration of exposure, and (3) cumulative exposure. None of the exposure metrics showed an effect on incidence for lung, breast, and brain cancer, nor any of the assessed subtypes in men and women. Of the hemato-lymphoproliferative malignancies in men, ever high exposed to ELF-MF showed a significant association with acute myeloid leukemia (AML) [hazard ratio (HR) 2.15; 95 % confidence interval (CI) 1.06-4.35] and follicular lymphoma (FL) (HR 2.78; 95 % CI 1.00-5.77). Cumulative exposure to ELF-MF showed a significant, positive association with FL but not AML among men. In this large prospective cohort study, we found some indications of an increased risk of AML and FL among men with occupational ELF-MF exposure. These findings warrant further investigation.

Reproductive factors and lymphoid neoplasms in Europe: findings from the EpiLymph case–control study

The study of lymphomagenesis has rarely focused on hormonal factors. Higher incidence rates are observed for many lymphoma subtypes in men compared with women suggesting an underlying association. Our goal was to investigate the association between reproductive factors and lymphomas. The Epilymph study is a multicenter case-control study carried out in six European countries from 1998 to 2004. Female cases of mature T-cell neoplasms (n = 52), Hodgkin lymphoma (n = 147), and mature B-cell neoplasms (n = 795), including its common subtypes, and their respective controls (n = 1,141) frequency matched by age, gender, and center were considered. An odds reduction of 29% (95% CI -46 to -6%) was observed for mature T-cell neoplasms for each child increase among parous women and of 13% (95% CI -19 to -7%) for mature B-cell neoplasms; while no association was observed for Hodgkin lymphoma. By B-cell neoplasm subtypes, these associations were found for chronic lymphocytic leukemia/small lymphocytic lymphoma (-21%, 95% CI -31 to -9%) and diffuse large B-cell lymphoma (DLBCL; -14%; 95% CI -23 to -3%). Overall, no associations were observed with age at first and last pregnancy, and ever use of hormonal contraceptives and lymphoma. Higher odds ratios for a short-term use of hormonal contraceptives (<5 years), but not for a long-term use, were observed for mature B-cell neoplasms, DLBCL, and follicular lymphoma compared with never use. These data support the hypothesis that increased parity confers a protective effect against lymphoma. Less clearly, our results also indicate that hormonal contraceptives could play a role.

Diabetes and Thyroid Cancer Risk in the National Institutes of Health-AARP Diet and Health Study

We hypothesized that diabetes may play a role in thyroid cancer risk due to the parallel secular rise in diabetes prevalence and morbidity in the United States, the higher prevalence of thyroid disorders among diabetics compared with the general population, and the potential roles of metabolic syndrome, obesity, and diabetes as precipitating factors in cancer development. We assessed the association between self-reported diabetes and the risk of differentiated thyroid cancer in the NIH-AARP Diet and Health Study, a prospective cohort of 200,556 women and 295,992 men, 50-71 years of age, in 1995-1996. Diabetes status and information on potential confounders was ascertained using a self-administered questionnaire. During an average of 10 years of follow-up, 585 thyroid cancer cases were identified. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for thyroid cancer and thyroid cancer subtypes in men and women according to diabetes status. Nine percent of the total baseline cohort reported a history of diabetes (7% of women, 10% of men). A nonsignificant 25% increase in thyroid cancer risk (HR = 1.25; 95% CI: 0.95-1.64) was associated with diabetes. Among women, the risk was significantly increased (HR = 1.46, 95% CI: 1.01-2.10). The risk was not elevated among men (HR = 1.04, 95% CI: 0.69-1.58). In this cohort, diabetic women with differentiated thyroid cancer were at somewhat higher risk of follicular thyroid cancer (HR = 1.92; 95% CI: 0.86-4.27) than papillary thyroid cancer (HR = 1.25; 95% CI: 0.80-1.97). This study lends support to the hypothesis that diabetes increases the risk of differentiated thyroid cancer.

Epidemiology of non-B clade forms of HIV-1 in men who have sex with men in the UK

To describe the frequency and risk factors of non-B HIV-1 subtypes in men who have sex with men (MSM) in the UK. Observational study. MSM diagnosed with HIV-1 infection from 1980-2007, with HIV genotype held in the UK HIV Drug Resistance Database were identified. Protease and reverse transcriptase sequences were collected and viral clade determined using the REGA algorithm. Associations between demographic variables and subtype were analysed using logistic regression. The prevalence of non-B HIV-1 infection amongst MSM in the UK was 5.4% (437/8058). In the UK this increased with year of diagnosis from pre1996 to 2002, and has subsequently remained relatively stable at around 7-9% after 2002, with a recent increase in 2007 to 13%. Multivariate analysis showed that acquisition of non-B HIV-1 infection was independently associated with later year of HIV diagnosis (P < 0.001), black ethnicity (P < 0.001) and non-European country of birth (P = 0.01). Age was also associated with subtype with individuals aged 25-39 years being less likely to have non-B virus than those aged less than 25 years (P = 0.01). Restricting the analysis to white men born in the UK, the association between subtype and year of diagnosis remained statistically significant (P < 0.001), as did the association with age (P < 0.001). The number of MSM in the UK infected with non-B clade HIV-1 is increasing, suggesting that the sociodemographic boundaries between HIV-1 viral subtypes globally are diminishing. Should viral subtypes be relevant to clinical disease progression or vaccine design, the changing pattern of distribution will need to be taken into account.

Multiple endocrine neoplasia type 2

Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant cancer syndrome with major components of medullary thyroid carcinoma (MTC), pheochromocytoma and hyperparathyroidism. The disease is caused by germline mutations of the RET proto-oncogene. Subtypes of MEN 2 include MEN 2A, MEN 2B and familial MTC (FMTC) which differ in pattern of additional lesions or--in FMTC--lack of pheochromocytoma. In 2009, after extensive review of the literature, the guidelines of the American Thyroid Association made several recommendations regarding clinical and genetic diagnostic testing and treatment options. In this article, the recently published literature is reviewed and concerns regarding future perspectives are added. In particular, a critical handling of rare DNA variants and double mutations is necessary. Up to now, mutation-specific risk profiles and mutation-associated treatment recommendations are unavailable. We emphasise the need for approved centres for treatment of patients affected by MEN 2, not only adults but young children as well. As a high level of skill is required for endoscopic adrenal-sparing surgery, surgeons should declare their expertise before operating such patients. Registry-based follow-up should be mandatory including documentation of short- and long-term outcome in order to provide valid data for future counselling of patients with MEN 2.

Consumption of Aspartame-Containing Beverages and Incidence of Hematopoietic and Brain Malignancies

In a few animal experiments, aspartame has been linked to hematopoietic and brain cancers. Most animal studies have found no increase in the risk of these or other cancers. Data on humans are sparse for either cancer. Concern lingers regarding this widely used artificial sweetener. We investigated prospectively whether aspartame consumption is associated with the risk of hematopoietic cancers or gliomas (malignant brain cancer). We examined 285,079 men and 188,905 women ages 50 to 71 years in the NIH-AARP Diet and Health Study cohort. Daily aspartame intake was derived from responses to a baseline self-administered food frequency questionnaire that queried consumption of four aspartame-containing beverages (soda, fruit drinks, sweetened iced tea, and aspartame added to hot coffee and tea) during the past year. Histologically confirmed incident cancers were identified from eight state cancer registries. Multivariable-adjusted relative risks (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression that adjusted for age, sex, ethnicity, body mass index, and history of diabetes. During over 5 years of follow-up (1995-2000), 1,888 hematopoietic cancers and 315 malignant gliomas were ascertained. Higher levels of aspartame intake were not associated with the risk of overall hematopoietic cancer (RR for >/=600 mg/d, 0.98; 95% CI, 0.76-1.27), glioma (RR for >/=400 mg/d, 0.73; 95% CI, 0.46-1.15; P for inverse linear trend = 0.05), or their subtypes in men and women. Our findings do not support the hypothesis that aspartame increases hematopoietic or brain cancer risk.

Molecular Implications of RET Mutations for Pheochromocytoma Risk in Multiple Endocrine Neoplasia 2

Multiple endocrine neoplasia Type 2 (MEN 2) is an inherited cancer syndrome characterized by medullary thyroid carcinoma (MTC). The disease has three subtypes, which are distinguished by the presence of additional phenotypes. In particular, pheochromocytoma occurs in approximately 50% of patients with the MEN 2A or MEN 2B subtypes, but is not found in patients with the milder disease subtype, familial MTC (FMTC). All subtypes of MEN 2 are caused by activating mutations of the RET (REarranged in Transfection) proto-oncogene. RET encodes a transmembrane receptor tyrosine kinase, required for development of neuroendocrine cell types and the kidneys. All MEN 2 subtypes are associated with single amino acid substitution mutations that are found in either the extracellular domain or in the kinase domain of RET. There are strong genotype-phenotype correlations in MEN 2 between patient phenotype and the specific residue that is mutated. MEN 2A is primarily associated with substitutions at five extracellular cysteine residues, while 95% of MEN 2B is associated with a single methionine to threonine mutation in the kinase domain (M918T). In FMTC, RET mutations are more broadly distributed, with both extracellular cysteines and intracellular sites implicated. In all cases, MEN 2-RET mutations result in constitutive activation of the receptor, although the mechanism and relative functional effects of the mutations vary. Recent advances in functional characterization and development of molecular models of RET and of various MEN 2-RET mutants are helping us understand tissue-specific differences in oncogenic potential conferred by the different RET mutations. Here, we discuss and compare several well-characterized mutations of the extracellular and kinase domains, which have quite varied functional implications.

Do Testicular Seminoma and Nonseminoma Share the Same Etiology? Evidence from an Age-Period-Cohort Analysis of Incidence Trends in Eight European Countries

The incidence of the two main clinical subentities of testicular germ cell cancer (seminoma and nonseminoma) is increasing throughout Europe. Most studies have revealed little variation in risk factors between the two subtypes. This study compared generation-specific trends in eight European countries, hypothesizing that similar temporal pattern by birth cohort implied that seminoma and nonseminoma had a largely comparable etiology. The results are presented using the age-period-cohort model and the nonidentifiability problem highlighted by partitioning the age, period, and cohort effects in terms of their linear and curvature component parts, assuming a priori that cohort effects predominated. Despite uniform overall increases by calendar period, declining rates of nonseminoma but not pure seminoma were observed in the majority of countries during the 1990s. The subtype trends were, however, largely analogous on a birth cohort scale. Notable observations were a decline in rates of both subtypes among recent birth cohorts in Switzerland and a short-term wartime effect in several countries, involving an attenuation of increasing risk of both subtypes in men born in 1940 to 1945. Departures from the steady increases in testicular cancer over time were likely to occur for nonseminomas some years ahead of seminoma on a period scale. The importance of birth cohort coincided with the view that given a short time interval of susceptibility to exposures earlier in life and a biologically constant time to diagnosis, all temporal changes in rate-limiting exposures should appear as generational effects. Trends in seminoma and nonseminoma conform to largely the same temporal patterns on this scale, implying that they share important etiologic factors.

Male Versus Female Intimate Partner Violence: Putting Controversial Findings Into Context

Key Words: female violence, intimate partner violence, male The article Violence and Mental Health Outcomes in a New Zealand Birth Cohort is an empirically sound study that raises interesting questions for the field of domestic violence research. As noted by its authors, the study's strengths include the large representative sample, the prospective nature of the research, and the consideration of a variety of covariates of domestic Within this study, the authors have addressed a series of controversial issues, and their findings now become one new piece of the puzzle regarding how to conceptualize male and female intimate partner When attempting to fit this new piece into the puzzle, it is important to keep in mind the larger picture (which we might wish was neatly presented on the side of the puzzle box!) and the evolution of work in this area. How do the current findings fit into the existing empirical findings on partner violence? Rates of Male and Female Intimate Partner Violence First, as have many others, the authors find that among a community sample of young people, rates of male and female violence are equivalent (see review by Archer, 2000). Indeed, if anything, in such samples, women tend to be slightly more likely to engage in physical aggression than men (Archer). As the authors note, these findings are consistent with a growing body of literature studying young samples and community samples, but they are inconsistent with research examining severe levels of violence (e.g., studies of criminal behavior, stalking after separation or divorce, sexual aggression, emergency room visits, murder), which usually suggest that male violence is more problematic than female Unfortunately, studies such as the current one often do not include enough cases of severe violence to permit examination of gender differences in severe Thus, differences in findings across studies have been attributed to the samples studied, the measures used (e.g., the Conflict Tactics Scale does not adequately assess the context or consequences of violence), and the behaviors examined (e.g., studies that include measures of stalking and sexual aggression show higher rates of male violence). Given such discrepancies in findings, as the authors note, there is clearly a need for future research to provide an in-depth analysis of the way in which the gender ratio in the perpetration of domestic violence varies with the severity of violence. Until such work is accomplished, the field will continue to be divided into two camps: (a) those studying community and young samples and primarily minor violence, who argue that women and men are equally violent and (b) those studying samples experiencing severe violence, who argue that male violence is more problematic than female At this time, we do not understand the relationship between these two types of Certainly, some spouses who initially perpetrate minor violence will escalate their aggression over time, becoming engaged in more severe But longitudinal studies suggest that such escalation is not inevitable and that some couples maintain only minor levels of violence or even desist from violence over time. We do not fully understand which couples progress from minor to severe violence and whether couples change from common couple violence to intimate terrorism (i.e., terms coined by Johnson, 1995; Johnson & Ferraro, 2000) or whether these types of violence are distinct and independent phenomena. Based on our own work on batterer typologies, we have suggested that differences in the course of violence may best be predicted by individual, particularly male, characteristics, such that some subtypes of men (e.g., generally violent and antisocial men or men experiencing severe psychological distress and evidencing characteristics of borderline personality disorder) will engage in high levels of partner violence, whereas other subtypes of men (e. …

Vegetable and fruit intake and stroke mortality in the Hiroshima/Nagasaki Life Span Study.

Fruits and vegetables are known for their beneficial effects on chronic diseases. The purpose of the present study was to investigate the protective effect of a diet rich in fruits and vegetables on total stroke mortality and its 2 main subtypes in men and women separately. A prospective cohort study of 40 349 Japanese men and women was initiated in 1980-1981 and followed until 1998. Fruit and vegetable intake was assessed at baseline on the basis of the response to a food frequency questionnaire. During the 18-year follow-up period, deaths from stroke were registered. A total of 1926 stroke deaths were identified during the follow-up period. An increasing frequency of intake of green-yellow vegetables and fruit was associated with a reduced risk of death from intracerebral hemorrhage and cerebral infarction. Daily intake of green-yellow vegetables was associated with a significant 26% reduction in the risk of death from total stroke in men and women compared with an intake of once or less per week. The protective effect associated with daily fruit and vegetable intake was observed for both cerebral infarction and intracerebral hemorrhage mortality but was slightly stronger and clearer for infarction than for hemorrhage, with a 32% reduction in men and a 30% reduction in women. Daily fruit intake was associated with a significant 35% reduction in risk of total stroke in men and a 25% reduction in women and was equally strong for both intracerebral hemorrhage and cerebral infarction. Daily consumption of green-yellow vegetables and fruits is associated with a lower risk of total stroke, intracerebral hemorrhage, and cerebral infarction mortality. The protective effects are similar in both men and women.

Leukocyte subtypes in electroejaculates of spinal cord injured men

Trabulsi EJ, Shupp-Byrne D, Sedor J, Hirsch IH. Leukocytes subtypes in electroejaculates of spinal cord injured men. Arch Phys Med Rehabil 2002;83:31-4. Objectives: To determine the level of leukocytospermia and seminal leukocyte subtypes in men with spinal cord injury (SCI) and to compare the findings with those of fertile, able-bodied controls. Design: Prospective, controlled clinical trial. Setting: University infertility practice. Participants: Thirteen able-bodied fertile men age matched to 17 men with SCI seeking reproductive rehabilitation. Interventions: Vibratory stimulation and antegrade electroejaculation for SCI group; manual ejaculation for controls. Main Outcome Measures: Immunoperoxidase technique on a panel of antileukocyte monoclonal antibodies to obtain the leukocyte subpopulations: B cells, T cells, neutrophils, and macrophages. Immunohistochemical staining and scoring to obtain the mean number of leukocytes and spermatozoa per high power field. The ratios of leukocyte to sperm and leukocyte subtype to sperm were tabulated. Results: Total white blood cells, neutrophils, and macrophages in the SCI population were significantly higher than those in the ejaculates of controls. Although not significantly elevated, all the other evaluated subsets were higher in the SCI group then in the controls. Conclusions: Leukocytospermia appears to be a pervasive abnormality in the semen recovered from men with SCI. The SCI group had significant elevations of total seminal leukocytes after electroejaculation. Compared with controls, men with SCI had significantly more seminal neutrophils and macrophages. Asthenospermia, universally observed in men with SCI, may be attributable, among other causes, to leukocytospermia. © 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

Mutations of the RET proto-oncogene in the multiple endocrine neoplasia type 2 syndromes, related sporadic tumours, and hirschsprung disease.

The RET proto-oncogene codes for a receptor tyrosine kinase thought to play a role in the development of neural crest and its derivatives. Mutations in the RET proto-oncogene have been found in patients with the multiple endocrine neoplasia type 2 syndromes (MEN 2), the related sporadic tumours medullary thyroid carcinoma and pheochromocytoma, and familial and sporadic Hirschsprung disease, a syndrome of congenital absence of enteric innervation. Germline mutations in one of eight codons within RET cause the three subtypes of MEN 2, namely, MEN 2A, MEN 2B, and familial medullary thyroid carcinoma. Somatic mutation in an overlapping group of nine codons have been found in a proportion of sporadic medullary thyroid carcinoma and pheochromocytoma. In contrast to MEN 2, approximately 25% of patients with Hirschsprung disease have germline mutations scattered throughout the length of RET.

Mutations of the RET proto‐oncogene in the multiple endocrine neoplasia type 2 syndromes, related sporadic tumours, and Hirschsprung disease

The RET proto-oncogene codes for a receptor tyrosine kinase thought to play a role in the development of neural crest and its derivatives. Mutations in the RET proto-oncogene have been found in patients with the multiple endocrine neoplasia type 2 syndromes (MEN 2), the related sporadic tumours medullary thyroid carcinoma and pheochromocytoma, and familial and sporadic Hirschsprung disease, a syndrome of congenital absence of enteric innervation. Germline mutations in one of eight codons within RET cause the three subtypes of MEN 2, namely, MEN 2A, MEN 2B, and familial medullary thyroid carcinoma. Somatic mutation in an overlapping group of nine codons have been found in a proportion of sporadic medullary thyroid carcinoma and pheochromocytoma. In contrast to MEN 2, approximately 25% of patients with Hirschsprung disease have germline mutations scattered throughout the length of RET. Hum Mutat 9:97–109, 1997. © 1997 Wiley-Liss, Inc.