Risk Factors

• The lifetime probability of being diagnosed with cancer is approximately 40% in men and 38% in women.
• Tobacco use is the most common cause of cancer and is associated with lung, head and neck, esophageal, gastric, pancreatic, kidney, and bladder cancers.
• Diet, obesity, inactivity, alcohol abuse, and height have also been shown to be associated with increased risk of developing selected cancers.
• Chronic inflammatory states such as ulcerative colitis and infections such as HIV, hepatitis, Epstein–Barr virus (EBV), human papillomavirus (HPV), and Helicobacter pylori are also associated with increased cancer risk.
• Several familial cancer syndromes have been described and have important implications for cancer screening (Table 22-2).
  Table 22-2: List of Selected Familial Cancer Syndromes With High Penetrance

  Syndrome	Defect	Associated Cancer Type
  Ataxia-telangiectasia	ATM	Multiple; predominantly leukemia and lymphoma
  Birt-Hogg-Dube	BHD	Chromophobe RCC
  Bloom syndrome	BLM	Multiple
  Cowden syndrome	PTEN	Multiple; predominantly breast, thyroid, RCC, endometrial
  Familial adenomatous polyposis	APC	Colorectal, desmoid
  Fanconi anemia	DNA repair complex	Multiple; predominantly MDS and AML
  Hereditary breast–ovarian cancer	BRCA1 and BRCA2	Multiple; predominantly breast, ovarian
  Hereditary diffuse gastric cancer	CDH1	Gastric, lobular breast cancer
  Hereditary leiomyomatosis and RCC	FH	Papillary RCC
  Lynch syndrome (HNPCC)	Mismatch repair	Multiple; predominantly colorectal
  Hereditary papillary RCC	MET	Papillary RCC
  Juvenile polyposis syndrome	MADH4 (SMAD4), BMPR1A	Digestive tract and pancreas
  Li-Fraumeni syndrome	TP53	Multiple
  MEN type 1	MEN1	Islet cell tumors
  MEN type 2	RET	Medullary thyroid cancer
  Neurofibromatosis type 1	NF1	MPNST, glioma
  Neurofibromatosis type 2	NF2	Meningioma, glioma, schwannoma
  Nijmegen breakage syndrome	NBS1	Predominantly lymphoma
  Peutz–Jeghers syndrome	LKB1 (STK11)	Multiple; predominantly breast, GI, pancreas
  Retinoblastoma, hereditary	RB	Retinoblastoma, primitive neuroectodermal tumor
  Rothmund–Thomson syndrome	RECQL4	Osteosarcoma
  Tuberous sclerosis (TS)	TSC1, TSC2	RCC, giant cell astrocytoma
  von Hippel-Lindau	VHL	Clear cell RCC
  Xeroderma pigmentosum	Nucleotide excision repair	Multiple, cutaneous

  AML, acute myeloid leukemia; GI, gastrointestinal; HNPCC, hereditary nonpolyposis colorectal cancer; MDS, myelodysplastic syndrome; MEN, multiple endocrine neoplasia; MPNST, malignant peripheral nerve sheath tumor; RCC, renal cell carcinoma.

• Prior exposure to cytotoxic chemotherapy or radiation therapy is associated with an increased risk of developing secondary cancers. For instance, exposure to alkylating agents or topoisomerase II inhibitors increases the risk of developing treatment-related leukemia, and exposure to radiation therapy increases risk for developing cancers such as breast cancer, angiosarcoma, and osteosarcoma.