Familial MEN Research Articles

Prostate cancer screening-when to start and how to screen?

Prostate-specific antigen (PSA) screening reduces prostate cancer (PCa) mortality; however such screening may lead to harm in terms of overdiagnosis and overtreatment. Therefore, upfront shared decision making involving a discussion about pros and cons between a physician and a patient is crucial. Total PSA remains the most commonly used screening tool and is a strong predictor of future life-threatening PCa. Currently there is no strong consensus on the age at which to start PSA screening. Most guidelines recommend PSA screening to start no later than at age 55 and involve well-informed men in good health and a life expectancy of at least 10–15 years. Some suggest to start screening in early midlife for men with familial predisposition and men of African-American descent. Others suggest starting conversations at age 45 for all men. Re-screening intervals can be risk-stratified as guided by the man’s age, general health and PSA-value; longer intervals for those at lower risk and shorter intervals for those at higher risk. Overdiagnosis and unnecessary biopsies can be reduced using reflex tests. Magnetic resonance imaging in the pre-diagnostic setting holds promise in pilot studies and large-scale prospective studies are ongoing.

Reproductive hormones and metabolic syndrome in 24 testicular cancer survivors and their biological brothers.

Testicular cancer survivors have impaired gonadal function and increased risk of metabolic syndrome when compared to healthy controls. However, because of the fetal etiology of testicular cancer, familial unrelated healthy men might not be an optimal control group. The objective of this study was to clarify if testicular cancer survivors have impaired gonadal function and increased risk ofmetabolic syndrome when compared to their biological brothers. A cross-sectional study of testicular cancer survivors (ClinicalTrials.gov number, NCT02240966) was conducted between 2014 and 2016. Of 158 testicular cancer survivors included, 24 had a biological brother who accepted to participate in the study. Serum levels of reproductive hormones and prevalence of metabolic syndrome according to International Diabetes Federation Criteria and National Cholesterol Education Program (Adult Treatment PanelIII) criteria comprised the main outcome measures of the study. Median age was similar in testicular cancer survivors and their biological brothers [44years (IQR 39-50) vs. 46 (40-53)years respectively (p=0.1)]. In testicular cancer survivors, follow-up since treatment was 12years (7-19). Serum levels of luteinizing hormone and follicle-stimulating hormone were elevated (p≤0.001), while total testosterone, free testosterone, inhibin B and anti-Müllerian hormone were lower (p≤0.001) in testicular cancer survivors than in their biological brothers. The prevalence of metabolic syndrome was similar and apart from HDL-cholesterol, which was lower in testicular cancer survivors (p=0.01); there were no differences in the individual components of the metabolic syndrome between testicular cancer survivors and their brothers. In conclusion, gonadal function was impaired in testicular cancer survivors, while we did not detect any difference in the prevalence of metabolic syndrome between testicular cancer survivors and their biological brothers.

RET gene mutations and polymorphisms in medullary thyroid carcinomas in Indian patients

Germline mutations of RET gene are pathognomonic of multiple endocrine neoplasia (MEN; MEN 2A/MEN 2B) and familial medullary thyroid carcinoma (FMTC), constituting 25% of medullary thyroid carcinomas (MTCs). We investigated RET gene mutations and polymorphisms at exons 10, 11, 13, 14, 15 and 16 in 140 samples, comprising 51 clinically diagnosed MTC patients, 39 family members of patients and 50 normal individuals. The method of choice was PCR and direct nucleotide sequencing of the PCR products. RET gene mutations were detected in 15 (29.4%) patients, with MEN 2A/FMTC in 13 patients and MEN 2B in 2 patients. Further, 39 family members of seven index cases were analysed, wherein four of the seven index cases showed identical mutations, in 13 of 25 family members. We also examined single nucleotide polymorphisms (SNPs) in RET gene exons in 101 unrelated samples. Significant differences in the allelic frequencies of SNPs at codons 691, 769, 836 and 904 between patient and control groups were not observed. However, SNP frequencies were significantly different in the Indian group as compared with other European groups. We identified two novel, rare and unique SNPs separately in single patients. Our study demonstrated presence of MEN 2A/MEN 2B/FMTC-associated mutations in accordance with the reported literature. Thus, RET gene mutations in exons 10, 11, 13, 14, 15 and 16 constitute a rapid test to confirm diagnosis and assess risk of the disease in familial MEN 2A/MEN 2B/FMTC.

Clinical and histopathological characteristics of familial prostate cancer in Finland

• To describe clinical and histopathological characteristics of Finnish familial prostate cancer (PCa) through a detailed analysis of cases in families. • In total, 202 Finnish families with 617 histopathologically confirmed PCa cases of confirmed genealogy were collected. • Complete clinical data, including age and prostate-specific antigen (PSA) at diagnosis, stage, grade and primary treatment, were gathered. The mean (range) number of affected men per family was 3 (2-8). • All the available diagnostic biopsy samples (n= 323) were collected and regraded by the same uropathologist. • A population-based cohort of 3011 hospital district Pirkanmaa PCa patients was used as a control group. • The mean (range) year of diagnosis of PCa was 1993 (1962-2006) and the mean (range) age at diagnosis was 68 (43-98 years). • The median (range) primary PSA level was 12.0 (0.8-11 000) ng/mL. After regrading, the Gleason score was ≤6 in 38%, 7 in 37% and ≥8 in 25% of men. • The subset of familial PCa men diagnosed after 1995 had higher PSA levels (P= 9.9 × 10(-6) ) and an earlier age of onset (P= 1.7 × 10(-6) ) than men in the control group, although there were no differences in cancer-specific survival. • We observed an earlier age of onset and higher PSA in familial PCa. • However, differences between sporadic and familial or hereditary PCa cannot be truly solved until genetic testing of high-risk genes in addition to family history is used to define PCa families. • We also emphasize that, when histological samples are collected over a longer study period, reanalysis of the samples by the same experienced uropathologist should be considered.

The interplay of genres, gender, and language ideology among the Muskogee

Contrary to statements made by previous researchers, Muskogee women are linguistically active in ceremonial public spheres, though through the use of genres that differ significantly from men's. One of the genres performed in these contexts is gossip, which is described by some Muskogee men as a dangerous genre. This article explores why Muskogee women's and men's linguistic practices differ so strikingly in the ceremonial sphere, and what women achieve through their use of gossip. It is suggested that consideration of Muskogee language and gender ideologies in regard to these issues shows that gendered language use differences are rational and maintain balance between the genders. Insights from both ideologies also indicate that women's gossip is a powerful genre, the use of which is generally positive for Muskogee society. (Muskogee Indians, gender ideology, language ideology, gossip)* I N T R o D U C T I o N Attending gatherings and ceremonies during my dissertation research with the Muskogee Indians, a Southeastern Native American tribe, made me aware of differences between the linguistic behaviors of Muskogee and Anglo men and women in public space. I began by carefully documenting the behaviors and the settings in which the behaviors occurred, hoping that a relatively clear correlation among event, genre, and gender would emerge. However, it soon became obvious that, in order to come to grips with and explain the variation in linguistic behaviors among Muskogee men and women, I needed to explore and include aspects of Muskogee language and gender ideology. This article exposes how rich a description and explanation of linguistic behaviors can be when ideologies about distinct aspects of social life are included in the analysis. Muskogee gender ideology provides for gender roles that are complementary, with women in charge of the familial and domestic and men in charge of the extra-familial and commercial. In line with the observations of Rosaldo (1974:19), Ortner 1974, and others, the community's valuation of women's roles within society is lower than that of men's. Concomitant with this, men's speech is fre? 2006 Cambridge University Press 0047-4045/06 $12.0() 23 1 This content downloaded from 157.55.39.78 on Tue, 21 Jun 2016 05:30:46 UTC All use subject to http://about.jstor.org/terms

Gene diagnosis and clinical management of multiple endocrine neoplasia type 1 (MEN1)

Identification of the MEN1 gene as a disease gene for multiple endocrine neoplasia type 1 (MEN1) has made it possible to predict whether a family member of an MEN1 patient will suffer from the same disease. MEN1 mutations have been found in almost all cases with familial MEN 1, but in fewer cases with sporadic MEN1. We analyzed MEN1 mutations in the largest number of Japanese MEN1 patients, 17 families and 21 sporadic cases, and found 54 MEN1 mutant carriers and 30 non-carriers. Furthermore, we identified a MEN1 phenocopy: GH-secreting pituitary tumor and primary hyperparathyroidism, which develops at older ages. In this article, we discuss how to utilize MEN1 gene diagnostics for the clinical management of MEN 1 patients and MEN1 mutation carriers.

Enhanced sensitivity to alkylating agent in lymphocytes from patients with multiple endocrine neoplasia type 1

Chromosome instability is known to be associated with certain autosomal recessive cancer-prone disorders such as Fanconi's anemia. Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant disorder characterized by development of tumors in two or more endocrine organs, and chromosome instability in patients with MEN 1 has been described. The clinical features of MEN 1 are, however, distinct from other DNA instability syndromes except predisposition to tumors. Therefore, we reevaluated chromosome instability in patients with familial MEN 1. An increase in the frequency of chromosome aberrations was observed in MEN 1 patients but not in control subjects when peripheral mononuclear cells were exposed to an alkylating agent, diepoxybutane (DEB). DEB reduced survival of mononuclear cells in a dose-dependent manner in both MEN 1 patients and control subjects, but this effect was more prominent in MEN I patients. There was no apparent correlation between certain MEN1 gene mutations and sensitivity to DEB. From these results, we conclude that hypersensitivity to alkylating agents exists in patients with MEN 1. Molecular mechanisms of this phenomenon and relationship to tumorigenesis in endocrine organs should be elucidated.

Frequency of Facial Angiofibromas in Japanese Patients with Multiple Endocrine Neoplasia Type 1.

The high frequency of cutaneous manifestations in patients with multiple endocrine neoplasia type 1 (MEN 1) has recently been reported. Since prevalence of some cutaneous diseases varies among different ethnic groups, we examined the frequency of facial angiofibromas in Japanese patients with familial MEN 1. Among 27 patients with germline MEN1 gene mutation and one asymptomatic gene carrier, angiofibromas were identified in 43% (12/28) of the subjects. This frequency was significantly lower than that of Caucasian patients, but nonetheless almost equaled those of pituitary tumors and pancreas endocrine tumors. Angiofibromas should be considered as one of major manifestations in MEN 1 regardless of patients' ethnic origin, and clinicians should pay careful attention to the cutaneous lesions in patients with endocrine tumors.

Multiple endocrine neoplasia type I: general features and new insights into etiology

Multiple Endocrine Neoplasia Type I (MEN I), also known as Wermer's syndrome and by several other names, is characterized primarily by the presence of functioning and nonfunctioning tumors or hyperplasia of the pituitary gland, parathyroid glands, and pancreatic islet cells. MEN I syndrome may be familial as well as sporadic. The sporadic cases are characterized by endocrine tumors in two or more of the organs affected in familial MEN I

Lateral differences in schematic face encoding during dual-task performance with increasing levels of difficulty.

20 normal, right-handed, familial dextral men performed (a) unimanual finger tapping, (b) encoding of schematic faces at three levels of difficulty (3, 5, and 7 faces), (c) verbal production, (d) concurrent tapping and verbal production, and (e) concurrent tapping and face encoding. Subsequent recognition of faces was disrupted more by concurrent left-hand tapping than by concurrent right-hand tapping, supporting both the hypothesis that the right hemisphere mediates face encoding in adults and Kinsbourne and Hicks' (1978) "functional cerebral distance principle." Left- and right-hand tapping rate and variability were not asymmetrically affected by either verbal production or face encoding. While there was an increase in generalized interference effects on face encoding, the degree of asymmetry of the interference remained constant. In addition, as the difficulty of the memory task increased, variability of tapping rate decreased. This was discussed in terms of attention and automatic motor programming.

Serum pepsinogen I in familial multiple endocrine neoplasia type I.

An increased serum pepsinogen I (PG I) concentration has been reported to be a marker of inherited peptic ulcer disease. Since both the Zollinger-Ellison syndrome and hyperparathyroidism, components of the familial multiple endocrine neoplasia type I syndrome (MEN I), are often associated with peptic ulcer, we have studied serum PG I concentrations in members of six well-defined families with MEN I. Serum PG I concentrations in 20 family members with hyperparathyroidism ranged from 35 to 864 ng/ml compared to 21-92 ng/ml in 16 nonaffected MEN I members. However, serum PG I levels were significantly higher (P less than 0.01) in the hyperparathyroid patients with hypergastrinemia (PGI median 192, range 75-864 ng/ml) than in those with normogastrinemia (PGI median 75, range 35-139 ng/ml). In fact, five of seven patients with hyperparathyroidism and hypergastrinemia compared to only one of 13 hyperparathyroid patients without hypergastrinemia had increased serum PG I levels above 130 ng/ml. We conclude that in the MEN I syndrome, increased serum PG I levels are found in patients with Zollinger-Ellison syndrome but not in hyperparathyroid patients with normogastrinemia and not in nonaffected MEN I members. The results indicate that in familial MEN I, hyperpepsinogenemia I is not inherited as a genetic trait but suggest that the elevated serum PG I levels are secondary to chronic hypergastrinemia.