
.. STS occurs excessively among persons with certain heritable states including retinoblastoma, Li-Fraumeni syndrome, Gardner's syndrome, Werner's syndrome, nevoid basal cell carcinoma syndrome, neurofibromatosis type 1, and some immunodeficiency syndromes.   
&&url PMID: 93443162 

Inherited syndromes usually have damaged DNA in the germline, which predisposes the people to certain cancers. Everyone who has more than one cancer, or anyone with a family with multiple members having cancer,  should probably see a cancer geneticist for discussion of their family history, and possible testing.  Some people with a cancer syndrome will have obvious signs of the syndrome [see way below], but others will be apparently normal except for cancers and chromosomal analysis. 


<b>A population-based study of familial soft tissue tumors.</b>

We used the nationwide Swedish Family-Cancer Database to analyze the risk for soft tissue tumors in offspring by parental cancers and in siblings of soft tissue tumor probands. Additionally, risk for second cancer following soft tissue tumor was investigated. 

In offspring, 1488 soft tissue tumors were diagnosed between years 1958 and 1996. Groups of offspring were compared by calculating standardized incidence ratios (SIRs) for soft tissue tumors. 

Parental breast, prostate and connective tissue cancers were associated with offspring soft tissue tumors in sex- and age-specific groups. The SIRs were of borderline significance, suggesting a small etiological contribution by Li-Fraumeni syndrome. 

Soft tissue tumors conveyed a high risk of second soft tissue tumor, probably partially due to recurrences. However, the observed risk for second nervous system cancer was consistent with Li-Fraumeni syndrome. 

Other associations were unlikely to be due to Li-Fraumeni or other known syndromes, but they could be spurious findings arising from multiple comparisons. Among these, parental stomach cancer (SIR 3.19, 95% CI 1.69-5.17) and endocrine gland tumors (SIR 3.66, 95% CI 1.32-7.17), particularly parathyroid tumors (SIR 4.46, 95% CI 1.41-9.23), were associated with offspring fibrosarcoma, and <b>parental breast cancers with offspring leiomyosarcoma </b>(SIR 2.04, 95% CI 1.08-3.30).
&&url PMID: 11297891 


<b>Cancer in twins: genetic and nongenetic familial risk factors</b>
      
..Familial clustering has been observed for cancers that occur at specific sites. ...
The identification of familial effects for total cancer in this study is consistent with the idea that individuals may possess a genetic susceptibility to cancer in general
&&url PMID: 9048832 


<b>Inherited Syndromes and Carcinogenesis</b>
 
	A syndrome is a  group of symptoms that collectively characterize a disease, psychological disorder, or other abnormal condition.  The syndromes below have been associated with LMS in one way or another.  There are other syndromes which are no doubt waiting to be discovered.  Finding a syndrome as a cause for LMS can sometimes alert the family to testing other members for the condition.  And possibly instituting preventive measures.  

	A small percentage of all tumors have obvious familial clustering. The familial cancer syndrome is well defined for many cancers.  Traits of familial tumors are sequentially inherited by offspring through gametes [eggs and sperm] in a Mendelian fashion, most commonly in an autosomal-dominant manner. People with these syndromes have inheritable faulty genes or mutations of genes in the germ line [in the DNA in the egg or sperm]  that can be passed on to offspring.   
&&url PMID: 15375699

Carcinogenesis requires multiple genetic events. Some genes are closely related to the cell cycle and tumorigenesis; proto-oncogenes, tumor suppressor genes, and DNA mismatch repair genes. If these genes are faulty or mutated, they can cause transformation of normal cells to malignant cells.   A normal cell is able to acquire the characteristics of a malignant cell under the influence of many factors: multiple environmental factors and a personal genetic factor.
&&url PMID: 15375699
Related Articles: &&url   

 
<b>Carcinogenesis</b>

Cancers result from the accumulation of inherited and somatic mutations in oncogenes and tumor suppressor genes. These genes encode proteins that function in growth regulatory and differentiation pathways. Mutations in those genes increase the net reproductive rate of cells. 

Chromosomal instability (CIN) is a feature of most human cancers. Mutations in CIN genes increase the rate at which whole chromosomes or large parts of chromosomes are lost or gained during cell division. CIN causes an imbalance in chromosome number (aneuploidy) and an enhanced rate of loss of heterozygosity, which is an important mechanism of inactivating tumor suppressor genes. ...

Inactivation of both copies of a tumour suppressor gene is required for carcinogenesis, while germline deletion or inactivation of one copy results in an increase in the risk of cancer and is responsible for many of the known hereditary cancer syndromes. 

In contrast, activation of only one copy of a proto-oncogene is required for carcinogenesis.  [A proto-oncogene is a gene that when transformed into an oncogene, causes cancerous changes in the cell.  This could be a gene that normally directs cell growth, but is altered to promote or allow uncontrolled cellular growth.] 

Germline deletion or inactivation of one copy of a proto-oncogene halves the risk of activation at this locus....
&&url PMID: 11826018 
&&url PMID: 15613287 
&&url PMID: 15510167 
&&url PMID: 12496039 
&&url PMID: 15042667

 
<b>Syndromes</b>

SOME syndromes that are associated with LMS or sarcoma are listed below, more are continually discovered both from human genome studies and from doctors coming into contact by chance with two or more people with symptoms that are similar, and who document these syndromes in the medical literature.  

<b>Beckwith-Wiedemann Syndrome
*Carney's Syndrome
Congenital Immune Deficiency Syndromes [associated with EBV virus]
	Common Variable Immunodeficiency Syndrome
	Ataxia-telangiectasia
Congenital stenosis of the lower esophagus associated with leiomyoma and leiomyosarcoma of the gastrointestinal tract
*Cowden's Syndrome
*Familial ULMS, 
Gardner's Syndrome
Hemihypertrophy Syndrome
*Leiomyomatosis & Renal Cell Cancer Syndrome
*Leiomyomatosis [Familial] Syndromes
*Li-Fraumeni Syndrome
Lynch II Syndrome
*Neurofibromatosis
Nevoid Basal Cell Carcinoma Syndrome
Peutz-Jeghers Syndrome
Poland's Syndrome
*Retinoblastoma and LMS of the bladder syndrome
*Retinoblastoma predisposes to LMS
Rubinstein-Taybi Syndrome
Tuberous Sclerosis
Werner's Syndrome
Xeroderma Pigmentosum

*at least one member of the ACOR LMS list has been diagnosed with the asterisked syndromes.</b>

  
*********************
<b>Beckwith-Wiedemann Syndrome</b>
	A rare, overgrowth disorder in which babies are large at birth and may develop low blood sugar. Other common symptoms are a large tongue, large internal organs, and defects of the abdominal wall near the navel. Beckwith-Wiedemann syndrome increases the risk of developing certain cancers.  Caused by DNA damage, or from imprinting errors.	. 
&&url PMID: 12920477 
&&url PMID: 15172847

<b>*Carney's Syndrome, also called Carney"s Triad</b>
	Carney's syndrome, features gastrointestinal stromal tumors (GISTs), extra-adrenal paragangliomas, and pulmonary chondromas.
&&url PMID: 15633134

<b>Congenital Immune Deficiency Syndromes </b>
	Common Variable Immunodeficiency Syndrome
	Ataxia-telangiectasia
[associated with EBV virus. see Viral section.]

<b>Congenital stenosis of the lower esophagus associated with leiomyoma and leiomyosarcoma of the gastrointestinal tract</b>
&&url PMID: 3052220 

<b>*Cowden's Syndrome</b>
	Cowden's syndrome is either familial [autosomal dominant] or sporadic and is associated with usually postpubertal development of a variety of cutaneous, stromal and visceral neoplasms. The syndrome is associated with mutations of the PTEN gene
&&url PMID: 15920539

<b>*Familial ULMS,</b> no other identifiable symptoms.  
	We have had several pairs of sisters or mother and daughter that have had ULMS 
 
<b>Gardner's Syndrome</b>
	An inherited syndrome characterized by development of multiple tumors, including osteomas of the skull, epidermoid cysts, and fibromas before age 10 and of multiple polyposis predisposing to colon cancer.
&&url PMID: 6310993 
&&url PMID: 880110
&&url PMID: 1154213

<b>Hemihypertrophy Syndrome</b>
	Hemihyperplasia is characterized by asymmetric growth of cranium, face, trunk, limbs, and/or digits, with or without visceral involvement. It may be an isolated finding in an otherwise normal individual, or it may occur in several syndromes. Although isolated hemihyperplasia (IHH) is of unknown cause, it may represent one end of the clinical spectrum of the Wiedemann-Beckwith syndrome (WBS).
	 An association among many overgrowth syndromes and a predisposition to neoplasia is well recognized
&&url PMID: 12920477 
&&url PMID: 9781907

<b>*Leiomyomatosis & Renal Cell Cancer Syndrome</b>
	Multiple fibroid tumors and renal cancer, can be associated with LMS.
&&url PMID: 14708972
&&url PMID: 11865300
&&url PMID: 11549574
&&url PMID: 15579034
&&url PMID: 15523491
&&url PMID: 11248088

<b>*Leiomyomatosis [Familial] Syndromes</b>
	Multiple fibroids in different places in the body.  Sometimes undergo malignant transformation.
&&url PMID: 12920381
&&url PMID: 15581996
&&url PMID: 12469059
&&url PMID: 10502446

<b>*Li-Fraumeni Syndrome</b>
	Individuals are at risk for developing multiple cancers at unusually early ages. It may include cancers of the adrenal glands, brain, breast, bone, lung, melanoma skin cancer, pancreas, prostate, and germ cell ovarian and testicular cancer, as well as leukemia, lymphoma and soft tissue sarcomas. Additional cancer sites may include the larynx and stomach. Patients with this syndrome have a nearly 50% chance of developing an invasive cancer by age 30 (compared to 1% chance for general population). More than 90% of these patients will have cancer by age 70.
&&url PMID: 15342977 
&&url PMID: 12200603
&&url PMID: 11297891

<b>Lynch II Syndrome</b>
	Hereditary non-polyposis colorectal cancer (HNPCC) (Lynch syndrome) It is the most common of the hereditary colorectal cancers and accounts for 5-10% of cases. This is characterized by development of predominantly proximal colon cancers. The  Lynch type II patients have colon cancer as well as extra-colonic cancers.
&&url PMID: 12075754   Free Full Text of Article is Available.

<b>*Neurofibromatosis 1</b>
	NF1 is an autosomal dominant trait, but is also a sporadic mutation. NF1 is caused by abnormalities in one of the genes encoding a protein called neurofibromin.  It causes unchecked growth of neurofibromatous tissue in nerves, skin and subcutaneous tissue, Malignant transformation of tumors occurs in approximately 5-10% of affected individuals.
&&url PMID: 15237755 
&&url PMID: 14696791 
&&url PMID: 10603757
&&url PMID: 9892804
&&url PMID: 7596048

<b>Nevoid Basal Cell Carcinoma Syndrome</b>
	Basal cell nevus syndrome is an autosomal dominant inherited set of multiple defects involving the skin, nervous system, eyes, endocrine glands, and bones. The condition causes an unusual facial appearance and a predisposition for skin cancers. Children with this disease have wide set eyes, a broad nasal saddle, and a heavy protruding brow.  The hallmark of this disorder is the appearance of skin cancer (basal cell carcinoma) at or about puberty.
&&url PMID: 12712116
&&url PMID: 7839473

<b>Peutz-Jeghers Syndrome</b>
	Peutz-Jeghers syndrome: An autosomal dominant inherited disorder characterized by freckle-like spots on the lips, mouth and fingers, and polyps in the intestines. Patients are at increased risk for developing cancer of the esophagus, stomach, colon, rectum, breast, ovary, testis and pancreas. The risk of cancer in the Peutz-Jeghers syndrome is very high. Among 210 patients with the symdrome, the risk of developing noncutaneous cancer between the ages of 15 to 64 was 93%.
	Peutz-Jeghers syndrome is inherited in an autosomal dominant manner and is due to mutation in a gene on chromosome 19p13.3 called STK11 (serine/threonine-protein kinase 11) that appears to function as a tumor suppressor gene. Half of patients have an affected parent from whom they inherited an STK11 mutation and the other half have a new mutation in the STK11 gene. 
&&url PMID: 3972226

<b>Poland's Syndrome</b>
	Poland's syndrome is characterized by a congenital defect of the pectoralis major [shoulder muscle] associated with various types of abnormalities of the arm of the same side. It has been associated with malignancies including LMS.
&&url PMID: 11091704
&&url PMID: 1389652

<b>*Retinoblastoma predisposes to LMS</b>
	Retinoblastoma is a malignant tumor which usually appears in infants or young children. The genetic cause is described as a "two-hit" process. Normally, individuals have two good copies of the retinoblastoma gene (RB-1) on chromosome 13. The disease develops in individuals in which mutation has occurred in both copies of RB-1.
	The RB-1 gene carries the information for making a protein called pRB. This protein regulates cell division. When pRB is absent or defective due to defective copies of the gene, uncontrolled cell division occurs, and cancer results. pRB appears to be involved in many types of cancer besides retinoblastoma.  [RB1 Loss of a single copy of chromosome 13 in the general region of the RB1 gene was found in around 35% of sarcomas. ed]
	Genetic testing may be recommended to see if a defective gene has been inherited. 
&&url PMID: 15073867
&&url PMID: 12759785
&&url PMID: 12610106
&&url PMID: 12845276

<b>*Retinoblastoma and LMS of the bladder syndrome</b>
&&url PMID: 12610106
&&url PMID: 12845276
&&url PMID: 12100953 
&&url PMID: 11520280
&&url PMID: 11487082
  
<b>Rubinstein-Taybi Syndrome</b>
	Rubinstein-Taybi syndrome is a condition characterized by short stature, moderate to severe mental retardation, distinctive facial features, and broad thumbs and first toes. Other features of the disorder vary. There is an increased risk of developing noncancerous and cancerous tumors.. It is inherited in an autosomal dominant pattern.
&&url PMID: 7747773

<b>Tuberous Sclerosis</b>
	Tuberous sclerosis is a rare genetic, neurological disorder in which benign tumors affect the brain, eyes, skin and internal organs.  It is primarily characterized by seizures, mental retardation, and skin and eye lesions.  Individuals with tuberous sclerosis may experience none or all of the symptoms with varying degrees of severity.
&&url PMID: 3376367 
&&url PMID: 549122

<b>Werner's Syndrome	</b>
	Patients with Werner's Syndrome show a variety of the signs and symptoms of normal ageing at an early stage of their life; gray hair, alopecia, muscle atrophy, osteoporosis, cataracts, hypogonadism, diabetes mellitus, hyperlipidemia, atherosclerosis, malignancy, brain atrophy, and senile dementia.  Werner's syndrome is a rare autosomal recessive disorder with chromosomal instability caused by the mutation of RecQ type DNA/RNA helicase.
&&url PMID: 14586597
&&url PMID: 11138345 
&&url PMID: 11704945
&&url PMID: 15138723

<b>Xeroderma Pigmentosum</b>
	A hereditary disease with such extraordinary sensitivity to sunlight that it results in the development of skin cancer at a very early age.  XP patients lack the normal capacity to repair the DNA damage inflicted by UV light. Damage to DNA is cumulative and cannot be reversed, and recurrent exposure can cause the rapid development of growths on the skin and eyes. 20% of XP patients also develop one or more of the following problems: blindness, deafness, mental retardation, poor coordination, spasticity, or retarded physical growth. XP is inherited as an autosomal recessive trait 
&&url PMID: 2535083
&&url PMID: 2817979
