Lecture 11 Heredity and Cancer Many people believe that they are genetically at greater risk for cancer than they actually are 80 90 of cancers are due to environment and lifestyle Only 10 20 are due to heredity However this is a population risk not individual Some inherited mutations increase the risk of developing cancer to almost 100 How do you know if you are at risk A family history that might indicate an inherited gene mutation would include two or more of the following points Cancer in several closely related people on the same side of the family and in several generations Cancer at younger ages than usual breast cancer in your 30s More than one diagnosis of cancer in the same person Specific types of cancer that are linked to specific genes breast cancer and ovarian cancer or colon cancer and endometrial cancer How are Mutations Inherited Somatic mutations occur after conception Occur in any of the cells of the body somatic except in any of the cells of the body somatic except the germ cells sperm and egg thus not passed on to children Can cause cancer or other diseases Inherited mutations occur before conception occur in the germ cells sperm and egg thus ARE passed on to children Do Can cause cancer or other diseases Sporadic Cancer History Accounts for 80 90 of cancer diagnosis NOT inherited Familial Cancer History Familial and Hereditary cancers account for 10 20 of cancer diagnosis Occurs in families more often than would be expected by chance May indicate presence of a risk increasing gene mutation inherited or signal shared environmental or lifestyle factors Hereditary Cancer History An inherited mutation in a single major gene strongly contributes to the development of cancer or cancer related conditions within the family The Facts About Inherited Cancer Only 5 10 of all cancers are related to an inherited gene mutation The child inherits a higher risk of developing cancer sometime during his her life Inheriting the gene mutation does not mean that the child is born with cancer Many genes are involved in cancer formation therefore not everyone who inherits a gene mutation will develop cancer Genetic Terminology Homologous Chromosomes Contain genes for the same biological features in same position locus Such as eye color can be same or different Alleles Paired forms of a gene one on each homologue Traits Expressed Dominant A Dominant trait B Recessive trait d Genes Present Homozygous Dominant AA Heterozygous Bb Homozygous Recessive dd Penetrance Frequency with which an allele yields an expected traits in a population i e which gene do you see Genes Present Homozygous Dominant AA Heterozygous Bb Dominant Cancer Risk Syndrome CC Homozygous Recessive Recessive Cancer Risk Syndrome ee Traits Expressed Dominant Trait A Penetrance Complete Dominant Trait B Dominant Trait C in 90 of individuals Recessive Trait d Recessive Trait e in 80 of individuals Complete Incomplete 90 Complete Incomplete 80 a Recessive Cancer Risk Syndrome In hereditary cancer risk syndromes exhibiting a recessive pattern of inheritance such as xerodrerm pigmentosum two defective copies of a tumor suppressor gene must be inherited to create a high risk of developing cancer 50 chance of receiving mutation 25 chance of child receiving both muttions b Dominant cancer risk syndrome In cancer risk syndromes exhibiting a dominant pattern of inheritance such as familial retinoblastoma inheriting a single defective tumor suppressor gene is sufficient to confer a very high risk of developing cancer However mutation of the second copy of the gene is required before cancer actually arises 50 chance of children receiving single mutation 90 probability of second mutation arising in a single retinal cell Both involve inherited risk for developing cnacer The difference is in how many alleles you have to inherit to be at a high risk Behavior of Proto Oncogenes Compared with Tumor Suppressor Genes in Cancer Proto oncogene gain of function mutation oncogene cancer Tumor suppressor gene Loss of function mutation loss of function mutation cancer Hereditary Risk Examples Genes affecting DNA repair Xeroderma pigmentosum Genes involved in Tumor Suppression Retinoblastoma Typical Xeroderma Pigmentosum Pedigree Xerodrerma Pigmentosum requires 2 copies of mutant gene to inherited one from each parent recessive cancer risk syndrome Results in absence of DNA repair Each child will have a 50 chance of inheriting mutant gene from each parent overall probability is 50 50 25 Xeroderma Pigmentosum Patients are sensitive to UV sunlight could be fatal Suit designed by NASA Minimal sunlight exposure leads to skin cancer Camp Sundown in upstate NY allow kids to participate in normal recreation Familial Retinoblastoma Pedigree A non carrier child has a 1 in 20 000 chance of developing retinoblastoma In families of retinoblastoma survivors 50 of the children develop the disease 40 of retinoblastoma cases are familia the rest are sporadic no familial history Children with familial form develop multiple tumors sporadic cases typically have a single tumor Sporadic vs Familial Retinoblastoma 1 Egg sperm no mutation inherited 2 Mutation in one copy of RB gene occasionally occurs as cells divide 3 Mutation in second copy of RB gene occurs in a single retinal cell 4 Sporadic retinoblastoma nonhereditary 1 Egg and sperm 50 of inheriting RB mutation 2 Mutation in one copy of RB gene is inherited in all body cells 3 Mutation in second copy of RB gene occurs in a single retinal gene 4 Familial retinoblastoma hereditary Possible Benefits of Genetic Testing Allow for a more accurate assessment of cancer risk If positive doctors can screen earlier for cancers If results are negative individuals may not have to screen as aggressively Early cancer screening can be offered to other at risk family members if a mutation is identified No physical risks involved in genetic testing Possible Risks of Genetic Testing Genetic testing can be emotionally difficult regardless of the results Emotional stress on relatives who have no had genetic testing make assumptions about their own genetic status Health insurance coverage for cancer screening Possibility of employer or insurance provider discrimination based on genetic rest results Effects of Birth Year on Breast Cancer Risk from BRCA Mutation Women born after 1940 carrying mutation in BRCA 1 or 2 genes have higher breast cancer rates than women born before 1940 who carry the same mutations This difference
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