Hereditary Cancer Predisposition Genes

Practice flashcards covering various genetic genes, syndromes, cancer risks, clinical features, and management guidelines based on the provided lecture notes.

APC (Familial Adenomatous Polyposis)

A tumor suppressor gene inherited in an autosomal dominant ($AD$) manner; classic $FAP$ is characterized by $100+$ adenomas at younger ages, almost $100\%$ colorectal cancer ($CRC$) risk, osteomas, and Congenital hypertrophy of the retinal pigment ($CHRPE$).

ATM (Ataxia Telangiectasia)

A gene associated with progressive ataxia and telangiectasias on the eyes/ears, biallelic mutations cause childhood leukemias/lymphomas, and carriers have increased risks for adult Breast ($21-24\%$ for carriers), Pancreatic ($5-10\%$), and Ovarian cancer.

BAP1

A tumor suppressor gene associated with BAP1-related dermal lesions ($Spitz$ tumors), ocular melanoma ($31\%$), mesothelioma ($22\%$), and renal cancer ($10\%$).

BLM (Bloom Syndrome)

An autosomal recessive ($AR$) syndrome characterized by growth deficiency, sun sensitivity, and a 'slapped face' rash; the gene product dissolves $Holliday$ Junctions during homologous recombination.

BRCA1

A tumor suppressor gene involved in chromosome repair in response to double strand ($DS$) breaks, with a breast cancer risk of $60-72\%$ and ovarian cancer risk of $39-58\%$. Men have lower risks for male breast cancer and prostate cancer compared to BRCA2.

BRCA2

A tumor suppressor gene where biallelic inheritance causes Fanconi Anemia; it is associated with increased risks of male breast cancer ($1.7-7.1\%$), prostate cancer ($19-61\%$), and melanoma.

BRIP1

A gene involved in double strand breaks and interstrand crosslink repair; mutations are associated with a $5-15\%$ ovarian cancer risk, with risk-reducing salpingo-oophorectomy ($RRSO$) suggested at age $45-50$.

CDH1

A gene coding for E-cadherin involved in cell-cell adhesion; mutations cause Hereditary Diffuse Gastric Cancer ($HDGC$) characterized by a signet ring appearance and thickening of the gastric wall, and lobular breast cancer risk ($42\%$).

CDKN2A

Associated with FAMMM (familial atypical multiple mole melanoma), this gene carries high risks for melanoma ($28-76\%$) and pancreatic cancer (>15\%).

CHEK2

A tumor suppressor gene activated in double strand breaks that increases risk for Breast ($23-27\%$) and Prostate cancer.

FANCs (Fanconi Anemia)

A group of proteins involved in double strand break and interstrand crosslink repairs; biallelic mutations (typically $AR$) lead to bone marrow failure, pre/postnatal short stature, and skeletal malformations (upper limb).

MEN1 (Multiple Endocrine Neoplasia Type 1)

A tumor suppressor gene associated with the 'three Ps': Parathyroid (hyperparathyroidism), Pancreas (gastrinomas/ZES), and Pituitary (adenomas).

NF1 (Neurofibromatosis 1)

A gene in the $RAS$ pathway where mutations cause neurofibromas, Cafe au lait spots, Lisch nodules on the iris, and increased risks for breast cancer ($20-40\%$) and optic nerve gliomas.

PALB2

A gene that pairs with BRCA2 in homologous recombination; monoallelic mutations increase risks for breast, pancreatic, and prostate cancer, while biallelic mutations cause Fanconi Anemia.

PTCH1 / SUFU

Genes associated with Gorlin syndrome (nevoid basal cell carcinoma syndrome), causing multiple basal cell carcinomas ($BCC$), jaw keratocysts, and medulloblastoma ($5\%$).

PTEN (Cowden Syndrome)

A tumor suppressor gene characterized by macrocephaly, hamartomas, and cancer risks known by the mnemonic Cow BUToCK (Breast, Uterine, Thyroid, Colorectal, Kidney).

RB1

The first identified tumor suppressor gene, associated with retinoblastoma (>95\% risk by age $5$) and secondary sarcomas in teens; it functions in cell cycle regulation ($p110$).

RET (MEN2)

An oncogene where mutations cause Multiple Endocrine Neoplasia Type 2, specifically Medullary Thyroid Cancer ($95-100\%$), Pheochromocytoma ($50\%$), and Parathyroid disease ($20-30\%$).

SDH (Hereditary Pheochromocytoma/Paraganglioma)

A series of genes ($SDHB$, $SDHC$, $SDHD$, $SDHAF2$) where $SDHD$ and $SDHAF2$ exhibit paternal inheritance; they are associated with paragangliomas and pheochromocytomas.

STK11 (Peutz-Jeghers syndrome)

A tumor suppressor gene associated with gastrointestinal polyps and characteristic dark freckling (melanosis) around the mouth; carries high risks for breast ($32-54\%$) and colorectal ($39\%$) cancers.

TP53 (Li-Fraumeni syndrome)

Known as the 'Guardian of the Genome,' this tumor suppressor regulates the cell cycle and apoptosis; mutations cause Li-Fraumeni syndrome, characterized by the 'BBBB' cancers (Bone, Breast, Blood, Brain).

VHL (von Hippel-Lindau)

A tumor suppressor gene that normally inhibits induction of blood vessels; mutations lead to hemangioblastomas of the brain/spine, bilateral renal cysts/cancers, and pheochromocytomas.

Lynch Syndrome

Caused by mutations in DNA mismatch repair ($MMR$) genes ($MLH1$, $MSH2$, $EPCAM$, $MSH6$, $PMS2$), it is associated with Colorectal, Endometrial, and Ovarian cancers.

XP (Xeroderma Pigmentosum)

An autosomal recessive condition characterized by severe UV sensitivity, frequent sun-induced burns, and high risks for $BCC$, $SqCCa$, and melanoma of the skin and eyes.