CHAPTER 10 Test Your Knowledge
Driving Question 1
What are mutations, and how can they occur?
By answering the questions below and studying Infographics 10.1, 10.2, 10.3, and 10.4, you should be able to generate an answer for the broader Driving Question above.
KNOW IT
In an otherwise normal cell, what happens if one mistake is made during DNA replication?
a. Nothing; mistakes just happen.
b. A cell cycle checkpoint detects the error and pauses the cell cycle so the error can be corrected.
c. The cell will begin to divide out of control, forming a malignant tumor.
d. A checkpoint will force the cell to carry out apoptosis, a form of cellular suicide.
e. The mutation will be inherited by the individual’s offspring.
b
Why does wearing sunscreen reduce cancer risk?
a. Sunscreen can repair damaged DNA.
b. Sunscreen can activate checkpoints in skin cells.
c. Sunscreen can reduce the chance of mutations caused by exposure to UV radiation present in sunlight.
d. It doesn’t; sunscreen causes mutation and actually increases cancer risk.
e. Sunscreen can prevent cells with mutations from being destroyed.
c
Are all mutations bad? Explain your answer.
No. Some mutations may have no effect on the encoded protein (silent mutations). Other mutations may be beneficial.
USE IT
The mutation illustrated in Infographic 10.4 inserted an A in the third codon of the mRNA shown. Use the genetic code (Infographic 8.10, p. 176) to match each mutation below (all are mutations of the normal mRNA sequence shown in Infographic 10.4) with its effect on the protein.
Mutation
Substitution of an A for the C in the third codon
Substitution of a C for the U in the fourth codon
Substitution of an A for the first C in the second codon
Effect
____ Protein will have an incorrect amino acid in its sequence.
____ No impact on the protein
____ Protein will be shorter than normal.
Substitution of an A for the first C in the second codon: protein will have an incorrect amino acid in its sequence.
Substitution of a C for the U in the fourth codon: no impact on the protein
Substitution of an A for the C in the third codon: protein will be shorter than normal.
Driving Question 2
How does cancer develop, and how can people reduce their risk?
By answering the questions below and studying Infographics 10.3, 10.4, 10.5, and 10.7, you should be able to generate an answer for the broader Driving Question above.
KNOW IT
What are some differences and some similarities between tumor suppressor genes and oncogenes?
In their nonmutant states, both tumor suppressor genes and (proto-)oncogenes are important for proper cell cycle progression. In their mutant states, both contribute to the development and progression of cancer. Wild-type tumor suppressor genes act to prevent the cell cycle from progressing inappropriately (e.g., when there is rampant DNA damage). When mutated, tumor suppressor genes can no longer pause the cell cycle when necessary, and cells with DNA damage may continue to divide. Normal proto-oncogenes act to promote cell division in response to appropriate signals to divide. When proto-oncogenes are activated by mutation (to oncogenes), they continuously “push” cells to divide, even in the absence of growth-promoting signals.
What is the role of BRCA1 in normal cells?
BRCA1 is a tumor suppressor gene that encodes a protein involved in DNA repair of mutations.
Which of the following can cause cancer to develop and progress?
a. a proto-oncogene
b. an oncogene
c. a tumor suppressor gene
d. a mutated tumor suppressor gene
e. b and d
f. b and c
e
USE IT
What would you say to a niece if she asked you how she could reduce her risk of breast cancer? (Assume there is no family history of breast cancer.) How might each of your suggestions reduce her risk?
Given that there is no family history of breast cancer, it is unlikely that your niece has a mutation in BRCA1. Therefore, her risk-reduction strategies won’t need to include early breast cancer screening, but they should include avoiding known carcinogens (e.g., tobacco), maintaining a healthy weight, limiting alcohol consumption, and making informed decisions about hormonal treatments (e.g., birth control or postmenopausal hormone therapy) and, if possible, the timing of pregnancies.
Carcinogens such as tobacco increase cancer risk by causing mutations that may disrupt normal cell cycle progression. Obesity is a risk factor for many cancers, and postmenopausal obesity is a particular risk for breast cancer. Alcohol is also a risk factor for breast cancer. Some hormonal interventions can increase breast cancer risk (e.g., oral contraceptives increase risk, but this risk seems to be negated 10 years after stopping the use of oral contraceptives). For women who choose to have children, having the first child earlier in life, and having more children reduces the risk of breast cancer.
Why is age a risk factor for cancer?
It takes several mutations in the same cell before it becomes cancerous. The older a person is, the more time in which a number of potentially cancer-causing mutations can be acquired. These can be the result of the greater number cell divisions, as well as more time exposed to environmental carcinogens.
Driving Question 3
Why do people with “inherited cancer” often develop cancer at a relatively young age?
By answering the questions below and studying Infographics 10.1, 10.6, and 10.7, you should be able to generate an answer for the broader Driving Question above.
KNOW IT
A woman with a BRCA1 mutation
a. will definitely develop breast cancer.
b. is at increased risk of developing breast cancer.
c. must have inherited it from her mother because of the link to breast cancer.
d. will also have a mutation in BRCA2.
e. b and c
b
227
Which of the following family histories most strongly suggests a risk of inherited breast cancer due to BRCA1 mutations?
a. many female relatives who were diagnosed with breast cancer in their 70s
b. many relatives with skin cancer
c. many relatives diagnosed with skin cancer at an early age
d. many female relatives diagnosed with breast cancer at an early age
e. many female relatives with both early breast cancer and ovarian cancer
e
USE IT
Lorene Ahern was born with an inherited predisposition to cancer. At the cellular and genetic level, what was she born with? At birth, were cells in her breast genetically identical to cells in her liver? Now that she has breast cancer, are her cancer cells genetically identical to her normal breast cells? Explain your answers.
At birth, all of Lorene’s cells were heterozygous for the BRCA1 mutation. Her breast cells and her liver cells (in fact, all her somatic cells) were genetically identical. Over time, some of her breast cells sustained a deleterious mutation in the other allele of BRCA1. This caused a complete lack of function of BRCA1 in those cells, eventually leading to breast cancer. Her breast cancer cells not only have a second mutation in the second allele of BRCA1, they also have several other mutations. At this point, the breast cancer cells are not genetically identical to her other breast cells.
Which of the following women would be most likely to benefit from genetic testing for breast cancer?
a. a 25-year-old woman whose mother, aunt, and grandmother had breast cancer
b. a healthy 75-year-old woman with no family history of breast cancer
c. a 40-year-old woman who has a cousin with breast cancer
d. a 55-year-old woman whose older sister was just diagnosed with breast cancer
e. All women can benefit from genetic testing for breast cancer.
a
People like Lorene Ahern have inherited a mutated version of BRCA1. Why does this mutation pose a problem? Why are these people at high risk of developing breast cancer when they still have a functional BRCA1 allele? Describe how the protein encoded by normal BRCA1 compares to that encoded by mutant alleles of BRCA1.
BRCA1 encodes a protein that plays an important role in DNA repair: it is a tumor suppressor gene. A BRCA1 mutation in one allele means that cells are relying on the other (functional) allele of BRCA1. If a subsequent single mutation disrupts that other allele of BRCA1, that single mutation is sufficient to eliminate all BRCA1 function in the cell. This is because mutant alleles of BRCA1 encode proteins that cannot function in DNA repair.
MINI CASE
Nellie has a family history similar to Lorene Ahern’s. Nellie’s mother died at an early age from breast cancer, as did her maternal aunt (her mother’s sister). Nellie is not yet 35 but has started having annual mammograms. She has also been tested for BRCA1 and BRCA2 mutations. She has a BRCA2 mutation and is considering prophylactic surgery. Her younger sister, Anne, doesn’t want to know the results of Nellie’s genetic testing because if Nellie has a BRCA2 mutation, then there is a chance that Anne could have inherited the same mutation from their mother. Does Nellie or Nellie’s doctor have an obligation to tell Anne about the test results? What about Nellie’s older brother? Should he be told? There are personal and medical benefits and risks to consider here.
There are many ethical and privacy considerations here, and different people are likely to have different perspectives. This case highlights the fact that one person’s genotype can provide information about someone else’s possible or probable genotype. Nellie chose to be tested, and knowing that she is a BRCA2 carrier, she can make decisions about her medical care to reduce her risk. She likely sought testing under the assumption that her medical information is private. In the absence of Nellie’s genotype, Anne has no reason to suspect that their mother was a BRCA2 carrier (and therefore possibly also Anne herself). As soon as Nellie is confirmed as a carrier, it is known that their mother more than likely had the mutation, and that Anne may have inherited the same mutation. This has implications for Anne’s future breast cancer risk, regardless of whether the information is shared with Anne. Similarly, Nellie and Anne’s older brother can also be affected by the knowledge that he may be a BRCA2 carrier (by inheritance from his mother). His own risk for prostate and breast cancer could be elevated if he is a carrier, and if he is a carrier, he can pass the mutation to his daughters, elevating their risk.
INTERPRETING DATA
Refer to Infographic 10.8 to answer the following questions.
a. What is the average percentage of BRCA1 carriers who develop breast cancer by age 50?
b. Exactly how many times more likely are BRCA1 carriers to develop breast cancer by age 50 compared to the general population?
c. What is the average percentage of BRCA1 carriers who develop breast cancer by age 70%
d. Exactly how many times more likely are BRCA1 carriers to develop breast cancer by age 70 than the general population?
e. Why are both carriers and noncarriers more likely to have developed breast cancer by age 70 than by age 50?
a: 41.5%: b: 41.5% vs. 2% = ~21 times more likely; c: 71.5%; d: 71.5% vs. 12% = ~5.95 times more likely; e: Because cancer risk increases with age, as there has been more time for mutations to accumulate and longer exposure to environmental risks.
BRING IT HOME
If you wanted to change your lifestyle to reduce your risk of developing cancer, what specific steps could you take with respect to each of the following? Be as specific as you can. Take your age and gender into consideration as you consider each factor.
a. alcohol consumption
b. sun exposure
c. tobacco use
d. exposure to pesticides
e. meat preparation (cooking method)
a: Alcohol consumption is a risk factor for many cancers, including oral and breast cancer. Reducing alcohol consumption can reduce the risk of cancer, particularly of breast and oral cancer. b: Sun exposure is a risk factor for many kinds of skin cancer, including melanoma. Avoiding sun exposure, especially between 10:00 A.M. and 2:00 P.M., and wearing protective clothing and sunscreen can help limit exposure to mutagenic radiation in sunlight. c: Tobacco use is a risk factor for many cancers, including lung, oral, bladder and kidney cancer. This is true for both cigarettes and smokeless (chewing) tobacco. Chemical compounds in tobacco products can damage DNA and lead to mutations. People should avoid smoking and all forms of tobacco use, and seek help for quitting. d: Many pesticides are carcinogenic. The average consumer can reduce exposure to pesticides by washing fruits and vegetable. It is important that agricultural workers follow label instructions in applying pesticides and wear protective equipment when working with any carcinogenic chemicals. e: Cooking meat at high temperatures (e.g., on a very hot barbecue grill) can result in the formation of carcinogens resulting from the reaction of molecules in the meat with the high heat. Eating meat that has been cooked for longer times at lower temperatures reduces exposure to these carcinogens.