p16 Genetic Test Reporting Counseling Protocol Flip Chart

p16 Genetic Test Reporting Counseling Protocol Flip Chart

Chromosomes, Gene, & Protein Cell Nucleus Chromosomes Gene Protein Adapted from Understanding Gene Testing,, NIH, 1995

Cancer Normal cell Disease of the cells Abnormal reproduction of cells causing an overload First mutation Second mutation Third mutation Malignant cell Fourth + mutation

All Cancer is Genetic Not All Cancer is Inherited Normal cell First mutation First mutation Second mutation Second mutation Third mutation Cancer cell Fourth + mutation Third mutation Cancer cell Fourth + mutation

Melanoma Is Sporadic or Hereditary Hereditary Sporadic MM, 56 MM x 2 Non MM Skin cancer MM 57 MM 25 MM 40 3 or more melanomas in a family Multiple MM in one individual Melanoma and pancreatic cancer Family history of melanoma or other skin cancers

The Development of Hereditary Cancer 2 normal genes 1 damaged gene 2 damaged genes 1 normal gene Tumor develops In hereditary cancer, one damaged gene is inherited. 1 damaged gene 1 normal gene 2 damaged genes Tumor develops

What Is Melanoma? Deadly skin cancer Begins in Melanocytes Tendency to spread

Relative Risk for Developing Melanoma (Relative risk indicates degree of increased risk compared to the general population) Risk Factor Skin Type I (fair skin) Freckling Blue Eyes Red Hair History of blistering sunburn 6 atypical nevi 10 dysplastic nevi 100 or more nevi* Family history of melanoma ** Previous primary cutaneous melanoma Member of melanoma prone family*** Member of a melanoma prone family, no personal hx melanoma, dysplastic nevi Member of melanoma prone family, personal hx melanoma, dysplastic nevi Approximate/Estimated Relative Risk 1.4 2-3 1.6 2.4-4 2-3 6.3 12 3.1-16.5 2-3 8.5 Up to 35-70 184 500 *Relative risk in the UK population ** One or more affected first-degree relatives *** Multiple affected relatives on the same side of the family

Melanoma is a multi-step process Adapted from Bennett, D. Oncogene 2003.

The p16 Gene p16 gene Chromosome 9

How p16 is Inherited Parents p16 / p16 p16 / p16 Children (50% chance) p16 / p16 p16 / p16 p16 / p16 p16 / p16

p16 Risk for Cancer 80 70 60 50 40 30 20 10 0 Melanoma Pancreatic? Other Melanoma Pancreatic? Other

Other Recent epidemiological evidence suggests that members of melanoma prone families may be at a higher risk for the following cancers: Breast Prostate Non- Hodgkin's Lymphoma Colon Multiple Myeloma CNS

Risk of Melanoma in p16 Mutation Carriers By age 50 By age 80 Risk in general population Risk in p16 mutation carriers in the United States <1% 1% ~50% ~76% J Natl Cancer Inst 2002; 94: 894-903

Risk of Pancreatic Cancer in p16 Mutation Carriers By age 75 Risk in general population Risk in some p16 mutation carriers ~ 1% 1 ~17% Int J Cancer 2000;87:809-11

Melanoma Risk in p16 positive vs. p16 negative Lifetime risk to carriers 53 times that of general population 33 times that of non-carrier family members within a p16 family Lifetime risk to non-carriers in mutation carrying family ~1.7 fold higher than general population

Managing the Cancer Risk of p16 Mutations Lifestyle: Minimize sun exposure Prevent sunburns Surveillance: Monthly self-exams Clinical exam every 6-12 months (begin age 10) Baseline photography of entire body (where available) Surgical: Prophylactic excision of suspicious nevi J Clin Oncol 1999;17:3245-51

Medical Management of Melanoma All individuals in familial melanoma families, regardless of p16 status, should have: Baseline total body skin exam at 10y w/ characterization of moles mole-mapping helpful and self skin exam education Physical exam every 6 mo until nevi stable and pt is capable of self exam (more freq - puberty & pregnancy) Monthly total body self-examination of skin Sun protection measures

Sun Avoidance and Protection

Sun Avoidance and Protection Prevention Avoid the sun between 10 am & 4 pm. Seek shade! Use sunblock with SPF 30 or higher. Re-apply every 2 hours Wear protective clothing Screening & Early Detection Practice skin self exam. Watch for growth or changes in a growth or mole Report any changes to your doctor

Interpreting a Negative Result MM MM + p16 mutation MM MM MM MM -p16 mutation MM Inconclusive -p16 mutation True negative Adapted from ASCO