Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

From a review of the records of 2,302 patients with retinoblastoma collated from CPMC and AFIP, it was found that retinoblastoma patients who survived their original eye cancer have a high incidence of second nonocular malignancies. The second neoplasms occur almost exclusively (97.5%) in patients who have had bilateral retinoblastoma, although retinoblastoma is much more commonly unilateral. The second neoplasms have appeared between 1 and 42 years after the successful treatment of retinoblastoma and have been fatal in approximately 85% of cases. Seventy-one percent of patients develop tumors in the field of the radiation beam; many of these were following treatment with low doses of radiation and after short latent periods. Nineteen percent of patients develop tumors clearly out of the field of radiation (eg, osteogenic sarcoma of the femur). Retinoblastoma patients appear to be unusually radio-sensitive to low doses of radiation and develop tumors in the field of radiation following treatment of 3,500 rads. They have a high incidence of nonocular tumors clearly distant from the radiation beam develop nonocular malignancies even if no radiation has been given. The incidence of multiple malignancies in patients successfully treated for retinoblastoma appears to be higher than for any other primary malignancy whether they receive radiation or not.
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PMID:Nonocular cancer in retinoblastoma survivors. 106 69

The cancers covered in this chapter are those of the eye, brain and nervous system, thyroid, bone and connective tissue. Generally, detailed interpretations of data on cancers of the bone and connective tissue are inadvisable owing to small numbers of patients and major changes in diagnosis and registration over time. A slight but steady increase in survival was observed among patients diagnosed in 1943-87 with cancer of the eye. Relative five year survival increased from 60 to 68% in men and from 61 to 74% in women during the 45-year period. The predominant type of eye cancer seen in children, retinoblastoma, had a very favourable prognosis, with a relative five year survival rate of more than 80% since around 1960. Since that time, overall survival for patients with cancers of the brain and nervous system also increased. Relative five year survival improved from 25 to 36% in men and from 34 to 48% in women during 1960-85. Our data do not indicate to which extent therapeutic and diagnostic advances underlie the improvement in survival. Overall survival of patients with thyroid cancer also increased during 1943-87. Relative five-year survival improved from 26 to 58% in men and from 28 to 68% in women. Some of the improvement reflects earlier diagnosis of localized tumours, particularly in young women. A substantial improvement in survival was observed among children and adolescents (< 20 years) diagnosed in 1943-87 with primary bone cancers. Over the study period, the relative five-year survival in that age category and increased from 25 to 48% in males and from 16 to 52% in females. Use of adjuvant chemotherapy in cases of Ewing's sarcoma and osteosarcoma contributed importantly to the improvement in prognosis. Overall survival of patients with soft-tissue cancer associated with no specific organ increased until approximately 1970, after which time no further improvement was observed. The decreased survival seen in women during the last decade of the study is puzzling; the increase in mean age at diagnosis would only partially explain it.
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PMID:Survival of Danish cancer patients 1943-1987. Eye, brain and nervous system, thyroid, bone and connective tissue. 851 38

In this study of cancer in offspring we demonstrate that factors linked to horticulture and use of pesticides are associated with cancer at an early age, whereas factors in animal husbandry, in particular poultry farming, are associated with cancers in later childhood and young adulthood. Incident cancer was investigated in offspring born in 1952-1991 to parents identified as farm holders in agricultural censuses in Norway in 1969-1989. In the follow-up of 323,292 offspring for 5.7 million person-years, 1,275 incident cancers were identified in the Cancer Registry for 1965-1991. The standardized incidence for all cancers was equal to the total rural population of Norway, but cohort subjects had an excess incidence of nervous-system tumours and testicular cancers in certain regions and strata of time that could imply that specific risk factors were of importance. Classification of exposure indicators was based on information given at the agricultural censuses. Risk factors were found for brain tumours, in particular non-astrocytic neuroepithelial tumours: for all ages, pig farming tripled the risk [rate ratio (RR), 3.11; 95% confidence interval (CI), 1.89-5.13]; indicators of pesticide use had an independent effect of the same magnitude in a dose-response fashion, strongest in children aged 0 to 14 years (RR, 3.37; 95% CI, 1.63-6.94). Horticulture and pesticide indicators were associated with all cancers at ages 0 to 4 years, Wilms' tumour, non-Hodgkin's lymphoma, eye cancer and neuroblastoma. Chicken farming was associated with some common cancers of adolescence, and was strongest for osteosarcoma and mixed cellular type of Hodgkin's disease. The main problem in this large cohort study is the crude exposure indicators available; the resulting misclassification is likely to bias any true association towards unity.
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PMID:Cancer in offspring of parents engaged in agricultural activities in Norway: incidence and risk factors in the farm environment. 854 94

Retinoblastoma is the most common eye cancer in children. Numerous families have been described displaying reduced penetrance and expressivity. An extensive molecular characterization of seven families led us to characterize the two main mechanisms impacting on phenotypic expression, as follows: (i) mosaicism of amorphic pathogenic variants; and (ii) parent-of-origin-effect of hypomorphic pathogenic variants. Somatic mosaicism for RB1 splicing variants (c.1960+5G>C and c.2106+2T>C), leading to a complete loss of function was demonstrated by high-depth NGS in two families. In both cases, the healthy carrier parent (one with retinoma) showed a variant frequency lower than that expected for a heterozygous individual, indicating a 56-60% mosaicism level. Previous evidences of a ~3-fold excess of RB1 maternal canonical transcript led us to hypothesize that this differential allelic expression could influence phenotypic outcome in families at risk for RB onset. Accordingly, in five families, we identified a higher tumor risk associated with paternally inherited hypomorphic pathogenic variants, namely a deletion resulting in the loss of 37 amino acids at the N-terminus (c.608-16_608del), an exonic substitution with a "leaky" splicing effect (c.1331A>G), a partially deleterious substitution (c.1981C>T) and a truncating C-terminal variant (c.2663+2T>C). The identification of these mechanisms changes the genetic/prenatal counseling and the clinical management of families, indicating a higher recurrence risk when the hypomorphic pathogenic variant is inherited from the father, and suggesting the need for second tumor surveillance in unaffected carriers at risk of developing adult-onset cancer such as osteosarcoma or leiomyosarcoma.
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PMID:Parent-of-origin effect of hypomorphic pathogenic variants and somatic mosaicism impact on phenotypic expression of retinoblastoma. 2966 54