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99 Cards in this Set
- Front
- Back
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Findings in ataxia telangiectasia
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broken vessels in eyes and ears, Purkinje cell loss, immunodeficiency, chromosomal breakage, premature ovarian failure, leukemia and lymphoma predisposition
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Females with ataxia telangiectasia are at risk for what?
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premature ovarian failure
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Describe Aarskog syndrome
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saddlebag (shawl) scrotum, cryptorchidism
broad forehead normal IQ widow's peak sandalfoot toe space thin upper lip with long philtrum short stature, short hands linear dimple below lower lip |
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Chromosome breaks and sister chromosome exchanges are a signature feature of what syndrome?
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Bloom syndrome
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Features of Bloom syndrome
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short stature, michrcephaly, malar hypoplasia, butterfly rash on face, leukemia in young, GI cancer in old
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The protein causing Bloom syndrome in in which gene family?
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RecQ family of helicases
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Gene assoc. with Bloom syndrome
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BLM on chromosome 15q26.1
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What breast biopsy findings are associated with No increased risk of cancer?
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adenosis, apocrine change, duct ectasia, mild hyperplasia
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What breast biopsy findings are associated with SLIGHTLY increased risk of cancer?
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hyperplasia that is mild or florid, sclerosing adenosis
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When a woman has atypical hyperplasia of breast tissue but no family history of breast cancer, what is her lifetime risk of developing breast cancer?
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20-25% cumulative lifetime risk
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When a woman has atypical hyperplasia of breast tissue AND a family history of breast cancer, what is her lifetime risk of developing breast cancer?
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up to 40% cumulative lifetime risk
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What type of DCIS has the higher chance of becoming invasive?
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Comedo type
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BRCA2 lifetime risk of breast cancer? ovarian cancer? male breast cancer?
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lifetime risk=50-85%
ovarian cancer =10-20% male breast=5-10% |
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Other cancers assoc. with BRCA2
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prostate, pancreatic, melanoma
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About what % of high-risk pancreatic cancer families have BRCA2 mutations?
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about 6%
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Typical risk of pancreatic cancer in BRCA2
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3-5%
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2 different alleles of BRCA 2 mutations can lead to what?
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Fanconi anemia
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Describe Fanconi anemia
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rare recessive childhood disease causing increased risk of leukemia and other cancers, skeletal and developmental anomalies, short stature.
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Name the 3 founder BRCA mutations for Ashkenazi Jews
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BRCA1--185delAG
BRCA1--5382insC BRCA2--6174delT |
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Recommendations for a woman who screens positive for BRCA
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Breast screening starting at 25:
mammogram every 12 months clinical breast exam -12 months self exam-6 months MRI-12 months Ovarian screening starting at 30-35: CA-125-12 months transvaginal u/s-12 months |
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Prophylactic ovary removal reduces BREAST cancer risk by how much in pre-menopausal women?
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over 50%
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Other cancers seen in HNPCC
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endometrial, ovarian, stomach, kidney, brain, otehr CNS, small bowel
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What is the first step in testing for HNPCC?
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If they pass Amsterdam criteria, then sequence MLH1 and MSH2.
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5 year survival rate fr ovarian cancer?
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45%
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Most ovarian cancers are of what type?
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surface epitheliaum-serous cells
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Recommendations for ovarian cancer screening for high-risk women
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Start 10 years before earliest case in family. Biannual rectopelvic exam with 6 month alternating CA125 and ultrasound.
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Ways to reduce risk of ovarian cancer
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oral contraceptives
pregnancy breastfeeding diet, exercise surgery (ligation, hysterectomy) |
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In surgical staging of ovarian cancer, what is the goal?
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Leave no tumor more than .5 cm in diameter. Remove and scrape everything, making chemo more effective.
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clinical and pathologic prognostic factors for ovarian cancer
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Stage
histologic type and grade age performance status volume of residual disease |
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What histologic types of ovarian cancer are worst?
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clear cell, mucinous, poorly differentiated
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Favorable findings for ovarian cancer prognosis
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Stage 1A or 1B
well-differentiated tumors no surface tumor growth confined to ovary no ascites negative peritoneal cytology |
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Unfavorable findings for ovarian cancer prognosis, requiring chemo
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ascites
poor differentiation surface tumor ruptured capsule positive peritoneal washing all stage 2 (no stage 1) |
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Chemo drugs for ovarian cancer: standard of care?
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Paclitaxel
(Taxane) + Carboplatin |
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Management of advanced ovarian cancer
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accurate and comprehensive surgical staging
cytoreduction postop chemo Taxane and Carboplatin |
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In ovarian cancer, what are goals of treatment in recurrent disease?
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quality of life
symptom control progression-free interval overall survival |
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In ovarian cancer, what determines whether a patient is drug-sensitive or resistant?
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Drug-sensitive=more than 6 months until recurrence
Drug-resistant=less than 6 months until recurrence Drug refractory=no response to initial therapy |
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A family pedigree iwth breast cancer and males with earlier-onset prostate cancers suggests what gene?
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BRCA1
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Factors affecting BRCA penetrance
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hormones/reproductive factors
carcinogens modifier genes response to DNA damage |
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Possible ways that alcohol increases risk of breast cancer
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Effect on steroid hormone production
Influence of IGF Generation of free radicals, etc Interaction with low folate levels |
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Describe the Women's Health Initiative (WHI) study of 2003 and what was found.
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Randomized study to look at effects of hormone replacement therapy on breast cancer. Given placebo vs. Estrogen/progesterone. Slightly increased risk, but risk with estrogen alone. Increased risk of cardiovasc. disease also. We now think HRT ok for 5 years, protective for heart dis. in women in 50s.
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Name some concerns assoc. with mammography in BRCA mutation carriers
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exposure to radiation
increased breast density high incidence on interval concerns |
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Digital mammography is better than standard for whom?
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women under 50
women with dense breasts pre- or peri-menopausal women |
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Mammogran vs. MRI: whichis better for what?
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MRI is better for invasive timors
Mammogram better for DCIS |
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Advantages of breast MRI over mammogram?
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Picks up things not seen on mammogram
detects multifocal disease more preceise estimates of size and margins reduces biopsy number |
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Evidence supports the idea that which categories of women should have annual MRI?
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Women with 20-25% or greater risk of br. cancer by BRCAPRO or other based on Fam Hx
Women with BRCA mutation Untested first deg. relative of BRCA carrier |
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THe NIH consensus statement on prophylactic oophorectomy in BRCA carriers
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surgery at 35 or when childbearing complete
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Tubal ligation is assoc. with what decreased risk in ovarian cancer? How?
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30-40% decreased risk due to interruption of circulation, alterd hormone levels, blockage of carcinogens
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What is the purpose of the breast cancer prevention trial (BCPT)?
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To evaluate the effects of Tamoxifen in reducing:
invasive breast cancer breast cancer mortality cardio mortality bone fractures Found that Tamoxifen gives 50% reduction in new cancers |
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What is the STAR study, and what did it find?
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Tamoxifen vs. Raloxifene. Found that Realoxifene is as effetive for invasive disease, but less effective for in situ disease. Raloxifene more protective for uterine cancer and hyperplasia. Equal for heart disease.
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Advantages to calculating breast cancer risk based on family history
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Takes into account multiple variables:
environmental factors age of onset common cancers distinctive predisposition syndromes |
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2 Models for prior probability for Lynch syndrome (MLH1 and MSH2 only)
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Bayes Mendel
PREMM1, 2 |
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How many cases of thyroid cancer per year in the US?
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20,000
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What percent of non-skin cancer is thyroid (in the US)?
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1.8%
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Subtypes and percentages of thyroid cancer
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90% well-differentiated (mostly papillary, 10% follicular)
5-10% medullary small %=anaplastic, lymphoma, other |
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Of all thyroid cancer, what % is medullary? What % of that is genetic?
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10% of all thyroid cancer is medullary. Of that, 25% is genetic, 75% sporadic.
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Most genetic medullary thyroid cancer is due to what?
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MEN2A
20% of all medullary thyiod cancer, 80% of genetic medullary thyroid cancer. |
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Besides medullary thyroid cancer, what other abnormalities are seen in MEN2A?
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pheochromocytomas
hyperparathyroidism |
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Besides medullary thyroid cancer, what other abnormalities are seen in MEN2B?
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pheochromocytomas
mucosal neuromas intestinal gangioneuromas Marfanoid habitus problems with colonic function |
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What type of protein is RET? How does is cause tumerogenesis when mutated.
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proto-oncogene
Stuck in ON position, causes overproliferation. AD inheritance, dominant negative. |
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3 major risks assoc. with a RET mutation and percentages of each
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medullary thyroid cancer=100%
pheochromocytoma=50% hyperparathyroidism=10-20% |
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What % of MEN2 families have MEN2B?
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5%
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Testing for which metabolite is LESS reliable that RET gene testing?
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calcitonin
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What pathology result is highly suggestive of a mutation in RET?
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C-cell hyperplasia=carcinoma in situ for medullary thyroid. If no RET mutation found, seek research testing.
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In MEN2 patients, when should they be screened for pheochromocytomas?
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before any surgery
annually based on plasma metanephrines CT imaging every 3-5 years (controversial) |
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Age of onset of parathyroid tumors in MEN1
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20-25
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What are paragangliomas?
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Tumors that arise in neuroendocrine tissue
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Sympathetic paragangliomas are neuroendocrine tumors that secrete what?
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catecholemines
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Sympathetic paragangliomas are neuroendocrine tumors that are found where?
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Usually retroperitoneal, may be abdomen or thorax
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Parasympathetic paragangliomas are neuroendocrine tumors that are found where?
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head and neck
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Name 3 genetic syndromes assoc. with pheochromocytomas
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von Hippel-Lindau
MEN2 NF1 |
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3 main features of von Hippel-Lindau
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hemangioblastoma of brain, spine, retina
clear cell renal canc pheochromocytomas |
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PGL-1 (head and neck paragangliomas)--what gene?
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SDHD
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PGL-1 (head and neck paragangliomas)--inheritance pattern?
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AD, but tumors only develop if inherited from dad, due to maternal imprinting
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Biggest danger in PGL-4?
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50% of pheochromocytomas are malignant
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Inheritance of PGL-4
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AD, no maternal imprinting
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Guidelines for testing a patient for melanoma genes
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3 or more melanomas
or 1 melanoma and 2 or more cases of melanoma or pancreatic in FDR or SDR in same lineage |
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40% of hereditary melanoma is due to what gene?
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CDKN2A/p16
(FAMMM) |
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By age 80, risk for melanoma due to CDKN2A mutation
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58% in Europe
78% in US 91% in Australia |
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4 genes assoc. with familial melanoma
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CDKN2A
p14ARF CDK4 MC1R |
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Difference btwn pheochromocytomas in VHL vs. MEN2
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VHL=normetanephrine predominant
MEN2=metanephrine predominant |
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What % of melanoma is hereditary?
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5-12%
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Up to what % of Gorlin is de novo?
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30%
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Dx criteria for Gorlin
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2 major 1 minor,
or 1 major 3 minor |
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Major features of Gorlin
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multiple basal cell skin cncers
skull calcium deposits jaw keratocysts palmar/plantar pits FDR with Gorlin |
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Minor features of Gorlin
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medulloblastoma in childhood
macrocephaly cleft lip/palate bifid ribs polydactyly eye problems heart/ovarian fibromas abdominal cysts |
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Cancers assoc. with Xeroderma Pigmentosum
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basal cell carcinoma
squamous cell melanoma mucosal tissue an tongue cancers |
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How do you test for Xeroderma pigmentosum?
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9 complementation groups, and only 50% test positive. So test by checking cells response to UV radiation.
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Features of ataxia telangiectasia
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immunodeficiency
progressive cerebellar ataxia telangiectasias radiation sensitivity malignancy risk (leukemia, lymphoma) |
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Best way to test for ataxia telangiectasia
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Immunoblotting for ATM protein is more effective than genetic testing.
Also, serum AFP high in 95%. Radiosensitivity assay. May have 7;14 translocation. |
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Physical manifestations of Fanconi anemia
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short stature
changes in skin pigmentation radial malformations |
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Features of Fanconi Anemia
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short stature, skin pigmentation changes, radial malformations
progressive bone marrow failure myelodysplastic syndrome or AML solid tumors--head/neck, esophagus, cervix, liver |
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How does diagnostic testing work for Fanconi anemia?
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Subject cells to DNA damaging substances, measure chromosomal breakage and formation of radials
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How many complementation groups for Fanconi anemia? Most common?
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13 complementation groups
FANCA=66% |
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What % of retinoblastoma is unilateral? bilateral?
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unilateral=60%
bilateral=40% |
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With a negative Fam Hx, what % of unilateral retinoblastoma patients test positive for RB1? bilateral?
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with no family history, 15% of unilateral have RB1 mutation, 90% of bilateral have RB1 mutation
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What % of Wilms tumor patients have a family history?
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1-2%
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Overgrowth syndromes assoc. with Wilms tumor
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Beckwith-Weidemann
Isolated hemihypertrophy |
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Features of Beckwith-Weidemann
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macroglossia
ear creeases visceromegaly hemihyperplasia macrosomia omphalocele/abdominal wall defects neonatal hypoglycemia 8% malignancy risk (Wilms, hepatoblastoma, neuroblastoma and rhabdomyosarcoma) |
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Causes of Beckwith-Weieemann with percents
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loss of DMR2 methylation=50%
parental UPD=20% unknown=15% CDKN1C mutation=10% gain of DMR1 methylation=~5% duplication=less than 1% translocation/inversion=less than 1% |
