Cancer susceptibility and DNA repair — MCQs

A 42-year-old woman is seen by her primary care physician for her annual checkup. She has no current concerns and says that she has been healthy over the last year except for a bout of the flu in December. She has no significant past medical history and is not currently taking any medications. She has smoked 1 pack per day since she was 21 and drinks socially with her friends. Her family history is significant for prostate cancer in her dad when he was 51 years of age and ovarian cancer in her paternal aunt when she was 41 years of age. Physical exam reveals a firm, immobile, painless lump in the upper outer quadrant of her left breast as well as 2 smaller nodules in the lower quadrants of her right breast. Biopsy of these lesions shows small, atypical, glandular, duct-like cells with stellate morphology. Which of the following pathways is most likely abnormal in this patient?

A 45-year-old woman presents with heavy menstrual bleeding between her periods. The patient also complains of experiencing an irregular menstrual cycle, weight loss, bloating, and constipation. She has had 3 uncomplicated pregnancies, all of which ended with normal vaginal deliveries at term. She has never taken oral contraception, and she does not take any medication at the time of presentation. She has no family history of any gynecological malignancy; however, her grandfather and mother had colon cancer that was diagnosed before they turned 50. On physical examination, the patient appears pale. Gynecological examination reveals a bloody cervical discharge and slight uterine enlargement. Endometrial biopsy reveals endometrial adenocarcinoma. Colonoscopy reveals several polyps located in the ascending colon, which are shown to be adenocarcinomas on histological evaluation. Which of the following mechanisms of DNA repair is likely to be disrupted in this patient?

A 38-year-old man presents with concerns after finding out that his father was recently diagnosed with colon cancer. Family history is only significant for his paternal grandfather who also had colon cancer. A screening colonoscopy is performed, and a polyp is found in the ascending (proximal) colon, which on biopsy shows adenocarcinoma. A mutation in a gene that is responsible for which of the following cellular functions is the most likely etiology of this patient’s cancer?

While performing a Western blot, a graduate student spilled a small amount of the radiolabeled antibody on her left forearm. Although very little harm was done to the skin, the radiation did cause minor damage to the DNA of the exposed skin by severing covalent bonds between the nitrogenous bases and the deoxyribose sugar, leaving several apurinic/apyrimidinic sites. Damaged cells would most likely repair these sites by which of the following mechanisms?

A 54-year-old woman with breast cancer comes to the physician because of redness and pain in the right breast. She has been undergoing ionizing radiation therapy daily for the past 2 weeks as adjuvant treatment for her breast cancer. Physical examination shows erythema, edema, and superficial desquamation of the skin along the right breast at the site of radiation. Sensation to light touch is intact. Which of the following is the primary mechanism of DNA repair responsible for preventing radiation-induced damage to neighboring neurons?

A 5-year-old girl is brought to the physician by her mother because of a 1-month history of a painful ulcer on her face. She has developed painful sunburns in the past with minimal UV exposure. Examination of the skin shows a 2-cm ulcerated nodule on the left cheek. There are scaly, hyperpigmented papules and plaques over the skin of the entire body. Ophthalmologic examination shows decreased visual acuity, clouded corneas, and limbal injection. Examination of a biopsy specimen from the facial lesion shows poorly-differentiated squamous cell carcinoma. Impairment of which of the following proteins is the most likely cause of this patient's condition?

A 19-year-old woman presents to the physician for a routine health maintenance examination. She has a past medical history of gastroesophageal reflux disease. She recently moved to a new city to begin her undergraduate studies. Her father was diagnosed with colon cancer at age 46. Her father's brother died because of small bowel cancer. Her paternal grandfather died because of stomach cancer. She takes a vitamin supplement. Current medications include esomeprazole and a multivitamin. She smoked 1 pack of cigarettes daily for 3 years but quit 2 years ago. She drinks 1–2 alcoholic beverages on the weekends. She appears healthy. Vital signs are within normal limits. Physical examination shows no abnormalities. Colonoscopy is unremarkable. Germline testing via DNA sequencing in this patient shows mutations in DNA repair genes MLH1 and MSH2. Which of the following will this patient most likely require at some point in her life?

A 3-year-old male child is found to have a disease involving DNA repair. Specifically, he is found to have a defect in the endonucleases involved in the nucleotide excision repair of pyrimidine dimers. Which of the following is a unique late-stage complication of this child's disease?

A 47-year-old man presents to his primary care physician for fatigue. Over the past 3 months, his tiredness has impacted his ability to work as a corporate lawyer. He denies any changes to his diet, exercise regimen, bowel movements, or urinary frequency. His past medical history is notable for obesity, type II diabetes mellitus, and hypertension. He takes metformin and enalapril. His family history is notable for colorectal cancer in his father and paternal grandfather and endometrial cancer in his paternal aunt. He has a 20-pack-year smoking history and drinks one 6-pack of beer a week. His temperature is 98.8°F (37.1°C), blood pressure is 129/71 mmHg, pulse is 82/min, and respirations are 17/min. On exam, he has conjunctival pallor. A stool sample is positive for occult blood. A colonoscopy reveals a small hemorrhagic mass at the junction of the ascending and transverse colon. Which of the following processes is likely impaired in this patient?

An investigator studying DNA mutation mechanisms isolates single-stranded DNA from a recombinant bacteriophage and sequences it. The investigator then mixes it with a buffer solution and incubates the resulting mixture at 70°C for 16 hours. Subsequent DNA resequencing shows that 3.7 per 1,000 cytosine residues have mutated to uracil. Which of the following best describes the role of the enzyme that is responsible for the initial step in repairing these types of mutations in living cells?