Hereditary hyperparathyroidism-jaw tumor syndrome (HPT-JT) is an autosomal dominant disease (OMIM 145001) that has recently been mapped to chromosomal region 1q21-q32 (HRPT2). Here we report two families with HPT-JT syndrome in which adult renal hamartomas or cystic kidney disease were prominent associated features, possibly representing a new phenotypic variant of the HPT-JT syndrome. In the first family, renal lesions were present in five out of six affected individuals, whereas HPT and JT were seen in four and two cases, respectively. In the second family, JT was found in three of the five affected individuals and two affected members also exhibited polycystic kidney disease. The possibility of the latter cosegregating as a separate autosomal dominant gene can not be ruled out. A sex-dependent penetrance of primary HPT, resulting in predominantly male-affected cases was evident in the two families. Twenty microsatellite markers in the HRPT2 region were typed, in addition to markers in the multiple endocrine neoplasia (MEN) types 1 and 2 regions at 11q13 and 10q11. The disease in these two kindreds was linked to five markers in the 1q21-q32 region (logarithm-of-odds scores: 3.2-4.2), whereas linkage to the MEN1 and MEN2 regions was excluded. Meiotic recombinations detected in affected individuals placed the locus telomeric of D1S215, thus narrowing the HRPT2 region from > 60 to approximately 34 centimorgans. Loss of heterozygosity was studied in seven renal hamartomas from two affected individuals in the first family, as well as in a jaw tumor and a parathyroid tumor from the second family. All renal hamartomas showed loss of heterozygosity at the 1q21-q32 region. The losses invariably involved the wild type allele derived from the unaffected parent, suggesting the inactivation of a tumor suppressor gene in this region.
Despite evidence of in vitro neutralization of TNF functional activity and partial inhibition of other secondary biologic effects of IL-2, rhuTNFR:Fc does not reduce the clinical toxicity associated with high-dose IL-2 therapy. These results suggest that the toxicity and antitumor effects of IL-2 treatment are independent of circulating TNF.
Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant disease characterized by neoplasia of the parathyroid glands, the endocrine pancreas, and the anterior pituitary gland. In addition, families with isolated endocrine neoplasia, notably familial isolated hyperparathyroidism (FIHP) and familial acromegaly, have also been reported. However, whether these families constitute MEN 1 variants or separate entities remains speculative as the genetic bases for these diseases are unclear. The gene for MEN 1 has recently been cloned and characterized. Using single strand conformation analysis (SSCA) and sequencing, we performed mutation analysis in: a) a total of 55 MEN 1 families from 7 countries, b) 13 isolated MEN 1 cases without family history of the disease, c) 8 acromegaly families, and d) 4 FIHP families. Mutations were identified in 27 MEN 1 families and 9 isolated cases. The 22 different mutations spread across most of the 9 translated exons and included frameshift (11), nonsense (6), splice (2), missense mutations (2), and in-frame deletions (1). Among the 19 Finnish MEN 1 probands, a 1466del12 mutation was identified in 6 families with identical 11q13 haplotypes and in 2 isolated cases indicating a common founder. One frameshift mutation caused by 359del4 (GTCT) was found in 1 isolated case and 4 kindreds of different origin and haplotypes; this mutation therefore represents a common "warm" spot in the MEN1 gene. By analyzing the DNA of the parents of an isolated case one mutation was confirmed to be de novo. No mutation was found in any of the acromegaly and small FIHP families, suggesting that genetic defects other than the MEN1 gene might be involved and that additional such families need to be analyzed.
Background: Over 114,000 new cases of lymphoid malignancies (LM), including Hodgkin lymphoma (HL), Non-Hodgkin lymphoma (NHL) and multiple myeloma (MM), are diagnosed annually. However, little is known about the influence of socioeconomic status (SES) on LM survival among Hispanics, who comprise 18% of the US population. This study evaluates the association between area-based SES and survival of Hispanic LM patients compared with non-Hispanic whites and non-Hispanics blacks. Methods: All LM reported to the NCI Surveillance, Epidemiology, and End Results Program (SEER-18) diagnosed between 2000-2015 were included. Census tract-level socioeconomic status (SES) was assessed in tertiles. Cox proportional hazards models estimated hazard ratios (aHR) to evaluate SES with cause-specific survival, adjusted for sex, stage at diagnosis, radiation, surgery and chemotherapy. All analyses were stratified by race/ethnicity. Results: Hispanics with low SES diagnosed with MM were 30% (aHR:1.3, 95% CI: 1.0-1.6) more likely to die from MM than those Hispanics with high SES. Whites and blacks with low SES diagnosed with MM were 20% (95% CIwhites: 1.1-1.3; 95% CIblacks: 1.0-1.4) more likely to die from MM than those with high SES. An association of low SES and death from NHL also found among Hispanics (aHR: 1.2; 95% IC: 1.1-1.5), whites (aHR: 1.3; 95% IC: 1.2-1.4) and blacks (aHR: 1.3; 95% IC: 1.0-1.7) compared to high SES groups. No association was found for HL. Conclusion: Low SES was associated with worse LM survival among different races/ethnicities. These results suggest SES is an important factor in determining long-term outcomes of patients diagnosed with LM.
Citation Format: Maira A Castaneda-Avila, Bill Jesdale, Mara Epstein. Association of lymphoid malignancies and area-based socioeconomic status with survival in the United States [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A102.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.