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Appendix 1

Head of Unit: Miguel Urioste

a. Some entities with autosomal dominant inheritance, in which the genetic analysis affects the clinical management
Pathology Incidence Gene Locus
Lynch Syndrome 1/200-1.000 MSH2 MLH1 MSH6 PMS2 2p21-p22 3p21.3 2p167p22
Hereditary breast / ovarian cancer (HBOC) 1/500-2.500 BRCA1 BRCA2 17q21.1 13q12.3
Multiple endocrine neoplasia, type 1 (MEN 1) 2-10/100.000 MEN1 11q13
Multiple endocrine neoplasia, type 2 (MEN 2) 1/25.000 RET 10q11.2
Familial adenomatous polyposis (FAP) 1/6.000-13.000 APC 5q21-q22
PTEN-hamartomas syndrome 1/200.000 PTEN 10q23.31
von Hippel-Lindau syndrome 1/36.000-45.000 VHL 3p25-p26
Hereditary retinoblastoma 1/13.500-25.000 RB1 13q14.1

In these families, the descendants of a carrier of the mutation have a 50% probability of inheriting the altered gene and of developing cancer during their lifetime.

b. Some entities with autosomal dominant inheritance, in which the genetic analysis has potential clinical value
Pathology Incidence Gene Locus
Tuberous Sclerosis or Bourneville disease 1/6.000-10.000 TSC1 TSC2 9q34 16p13.3
Familial melanoma 1/10.000 CDKN2A CDK4 9p21 12q14
Neurofibromatosis 1 1/3.500 NF1 17q11.2
Neurofibromatosis 2 1/40.000 NF2 22q12.2
Familial Paraganglioma Rare SDHB SDHC SDHDSDH5 1p36.1-p35 1q21 11q2311q13.1
Juvenile polyposis 1/100.000 SMAD4 BMPR1A 18q21.1 10q22.3
Beckwith-Wiedemann Syndrome 1/14.000 KIP2 y otros en 11p15.5 11p15.5
Birt-Hogg-Dubé Syndrome Rare FLCN 17p11.2
Gorlin Syndrome 1/57.000 PTCH1 PTCH2 9q22.31p32
Li-Fraumeni Syndrome Rare TP53 17p13.1
Peutz-Jeghers Syndrome 1/120.000 STK11 19p13.3
Familial Wilms Tumor 1/10.000 WT1 11p13

In these families, the descendants of a carrier of the mutation have a 50% probability of inheriting the altered gene that confers a high risk to develope cancer during their lifetime.

c. Some entities with autosomal recessive inheritance
Pathology Incidence Gene Locus
Fanconi Anemia 1/360.000 FANCA FANCB FANCC FANCD1 FANCD2 FANCE FANCF FANCG FANCI FANJ FANCL FANCM FANCN FANCO FANCP 16q24.3 Xp22.31 9q22.3 13q12.3 3p25.3 6p21-p22 11p15 9p1317q22 2p16.1 16p12 17q22 16p13.3 17q22 16p13
Ataxia-telangiectasia 1/30.000-100.000 ATM 11q22.3
Bloom Syndrome Rare RECQL3 15q26.1
Chediak-Higashi Syndrome Rare LYST 1q42.1-q42.2
Rothmund-Thomson Syndrome Rare RECQL4 8q24.3
Werner Syndrome 1/500.000 RECQL2 8p12-p1.2
Xeroderma pigmentosum 1/250.000-1.000.000 XPA XPC DDB2 y otros 9q22.3 3p25 11p11-p12

In these families, the descendants of a carrier of the mutation have a 50% probability of inheriting the altered gene; whether or not they will develop cancer during their lifetime is a more complex issue, and depends on the nature of the inherited gene and/or whether the other parent is also a carrier of the mutation.

d. Other entities with predisposition to cancer
Pathology Incidence Gene Locus
Esophageal cancer with palmoplantar tylosis Unknown
Hereditary diffuse gastric cancer Rare CDH1 16q22.1
Familial nonmedullary thyroid carcinoma Unknown
Familial prostate carcinoma Unknown
Familial renal cell carcinoma (clear cell) Unknown 3p?
Familial papillary renal carcinoma Rare MET 7q31
Carney complex Unknown PRKRA1A 17q23-q24
Congenital dyskeratosis Unknown DKC1 Xq28
X-linked lymphoproliferative Syndrome or Duncan disease Unknown SH2D1A Xq25
Sotos Syndrome Rare NSD1 5q35
Currarino Syndrome Unknown HLXB9 7q36

In these families, the descendants of a carrier of the mutation have a 50% probability of inheriting the altered gene; whether they will develop cancer during their lifetime depends on the inheritance model.