Gene Abnormality

Syndrome

Associated cancers

Other associated conditions

High Penetrance Genes

BRCA1

Hereditary breast-ovarian cancer syndrome

Breast, ovarian, pancreas, prostate cancers; primary peritoneal tumors, melanoma; Male breast cancer

BRCA2

Hereditary breast-ovarian cancer syndrome

Breast, ovarian, pancreas, prostate cancers; melanoma, primary peritoneal tumors; Male breast cancer

CDH1

Hereditary diffuse gastric cancer syndrome

Diffuse gastric cancer, lobular breast cancer, signet ring colorectal cancer

PTEN

Cowden syndrome (PTEN hamartoma tumor syndrome)

Major criteria: Endometrial cancer, Breast cancer, Thyroid cancer (follicular type)

Minor criteria: Colon cancer, Thyroid cancer (papillary type), Renal cell cancer

Major criteria: GI hamartomas, adult Lhermitte-Duclos disease, macrocephaly, multiple mucocutaneous lesions, pigmentation of the glans penis

Minor criteria: Autism spectrum disorder, ?3 lipomas, testicular lipomatosis, vascular anomalies, ?3 esophageal glycogenic acanthosis, thyroid nodules, IQ ?75, uterine fibroids

STK11

Peutz-Jeghers syndrome

Breast cancer

GI hamartomatous polyps

tp53

Li-Fraumeni syndrome

Soft tissue sarcoma, osteosarcoma, leukemia, lymphoma; Breast, brain, adrenocortical, colorectal, bronchoalveolar cancers

Intermediate Penetrance Genes

ATM

Ataxia-telangiectasia syndrome (Louis-Barr syndrome)

Non-hodgkin lymphoma, leukemia, medulloblastoma, basal cell carcinoma, gliomas; Breast, stomach, uterine, bladder, lung, pancreas, and ovarian cancers

Ataxia-telangiectasia

BARD1

Breast cancer, neuroblastoma

BRIP1

Breast cancer

Fanconi anemia

CHEK2

Prostate, breast, lung, colon, kidney, thyroid, ovarian cancers; brain tumors, osteosarcoma

PALB2

Breast cancer, pancreatic cancer

Fanconi anemia; tracheoesophageal fistula

Low Penetrance Genes

BLM      

Bloom syndrome

Acute leukemia, lymphoma, Wilms tumor; Breast, lung, cervix, tongue, larynx, esophagus, colon, skin cancers          

Microcephaly, telangiectasias, café-au-lait spots, sterility in males & decreased fertility in females; increased susceptibility to infections

CASP8

Breast , lung, hepatocellular cancer

Autoimmune lymphoproliferative syndrome

CTLA4*

Breast cancer

Autoimmune Addison disease, Graves disease, celiac disease, systemic lupus erythematosus, Hashimoto thyroiditis, rheumatoid arthritis, Type 1 diabetes

CYP19A1*

Breast cancer

Aromatase deficiency, aromatase excess syndrome

FGFR2

Stomach, prostate, cervical, breast, pancreas, head and neck cancers

Pfeiffer syndrome, Jackson-Weiss syndrome, lacrima-auriculo-dento-digital syndrome, Apert syndrome, Beare-Stevenson cutis gyrata syndrome, Crouzon syndrome

H19*

Breast cancer

Beckwith-Wiedemann syndrome, Russel-Silver Syndrome

LSP1*

Breast cancer

MAP3K1*

Breast cancer

Swyer syndrome

MRE11A

Breast, ovarian cancers

Ataxia-telangiectasia, nephronophthisis-related ciliopathies

NBN/NBS1

Nijmegen Breakage Syndrome

Breast, prostate, ovarian cancers; melanoma, leukemia

Growth deficiency, microcephaly, bird-like facies, recurrent infections

NF1

Neurofibromatosis Type 1 (von Recklinghausen disease)

Malignant peripheral nerve sheath tumor, astrocytoma, pheochromocytoma, carcinoid tumor, neuroblastoma, leukemia, Wilms tumor, sarcomas, ependymoma, primitive neuroectodermal tumor, breast cancer

Café-au-lait macules, ?2 neurofibromas, multiple axillary or inguinal freckles,

RAD50

Nijmegen Breakage Syndrome-like Disorder

Breast, ovarian cancers

Growth deficiency, microcephaly, bird-like facies

RAD51*

Breast cancer

Congenital mirror movement disorder

RAD51c

Breast, ovarian cancers

Fanconi anemia, tracheoesophageal fistulae

RB1

Hereditary Retinoblastoma

Retinoblastoma, various sarcomas, melanoma, brain tumors, leukemia, lymphoma, malignant phyllodes tumors

RINT1

Breast cancer

TERT*

Melanoma, AML, breast cancer

Dyskeratosis congenita, idopathic pulmonary fibrosis, isolated aplastic anemia

TOX3*

Breast cancer

Restless leg syndrome

XRCC2

Breast cancer

XRCC3

Breast cancer, cutaneous malignant melanoma 6