Cancer bad luck or bad genes Flashcards
3 categories of cancer
Genetic (small), familial (bigger), sporadic (biggest). Familial is something that is shared by the family that is not genetic (cultural, behavioural)
How much of cancer is multifactorial?
Roughly 90-95%. It’s an overlap and interplay b/w personal things, environment, and genetic
What is hereditary cancer?
Due to abnormality in single genes. Causes genetic syndrome. Passed from parent to child. Dominant and recessive varieties (cancer isn’t often recessive).
Types of hereditary cancer
Virually any solid tumour, hematological is rare except in recessive.
Most common cancers that are not hereditary
Lung (mostly due to exposure), and cervical (almost always due to infection)
Assessing the family history
How many total cancers in the family compared to the total number of individuals in there. See if there’s too much of one cancer types or if there are 2+ that are known to be related; if there are any special features of pathology; and is there the possibility of parent to child transmission
How many cases are needed for a significant family history?
Need 3+ of single type or associated types.
Challenges with interpreting pedigree
Penetrance - some people just never get cancer despite mutation. Expressivity - severity, age of onset, type of presentation are varied. Records that are not right. Lost info - early death so no show, preventative surgery, family rifts. Size of family (small family is sometimes hard) and parent of origin (can be different if from mom or dad)
How is Breast cancer inherited?
It is from both sides!! maternal and paternal
Hereditary Breast Ovary Syndrome
About 5-10% of breast cancer is hereditary. 1-2% of breast cancer is due to mutation in BRCA1 + 2 (BRCA is involved in 50% of breast + ovarian cancer). Can be due to other genes but no tests yet, and breast and ovarian cancer can come from other gene problems.
Who has BRCA 1/2 mutations?
50% of families with breast and ovarian cancer that meet high risk criteria. 20% of families with breast cancer only that meet high risk criteria. Men with breast cancer AND family history of it. Young cases - if solo - unlikely to be BRCA
Ethnic and geography factors in breast cancer
Ashkenazim Jews - 1% prevalence of BRCA1 and of 2. Common Eastern Europe mutations. Founder effects.
Genetic testing of BRCA1/2
Sequencing and MLPA.
What about tumor markers like Her2neu?
Many cancers are tested for certain markers. BC can have estrogen/progesterone receptors or her2neu, but these are changes in the tumor only! Not heritable, but useful for treatment
Bad luck examples.
Spontaneous - just one ancestor, low risk; or one from one side and one on other side, low risk. More concerning but still lower risk is a mother and sister with onset after 60.
