Mini-Med at McGill: Question and Answer Corner

Mini-Med Study Corner

Cancer Genetics: Genes and Dreams
Dr. Patricia Tonin

Written Question and Answer Section:

1. Can a genetic mutation develop without a family history and then in turn be passed on to offspring?

Yes. One possibility is that the mutation arises de novo. In this scenerio a new gene mutation arises in the germ cell (egg or sperm) of one of the parents or in the fertilized egg itself. The alteration in the gene is present for the first time in one family member. Once present the mutation can be transmitted to the offspring of affected individuals. Affected cases would appear depending on whether or not the disease is associated with one or both mutated copies of the gene.

For more information and specific examples please view Educational Materials, GeneReviews at:
www.ncbi.nlm.nih.gov/sites/GeneTests.

2. With today's knowledge, do you think Mammograms are a woman's first defence against breast cancer?

There are a number of factors associated with increased risk for breast cancer such as hormone therapy, ionizing radiation, obesity, alcohol and high risk cancer susceptibility genes. There are also a number of factors associated with decreased risk of breast cancer such as exercise, early pregnancy (full-term pregnancy) and breast feeding.

Interventions associated with decreased risk of breast cancer include selective estrogen receptor modulators (SERMs) and aromatase inhibitors or activators, and prophylactic mastectomy or oopheractomy or ovarian ablation.

A review of the level of evidence in support of these factors and the risks and benefits of interventions are summarized in the Breast Cancer Prevention (PDQ) available at:
www.cancer.gov/cancertopics/pdq/prevention/breast/healthprofessional

Mammography is used as a breast cancer screening tool. It cannot prevent the development of breast cancer. Routine mammographic screening is an accepted standard for the early detection of breast cancer in many countries. The goal of mammography is to identify breast cancer at its earliest stages when the disease is confined to the breast. There is evidence which shows that women diagnosed with early stage disease where the cancer is confined to the breast have an overall better outcome (5-year survival) than those where the disease has spread (metastasized) beyond the breast. At the present time mammography along with physical breast examination is the modality of choice for the detection of breast cancer at its earliest stages. The results of eight randomized trials, the NIH-ACS Breast Cancer Detection Demonstration Projects, and other research studies showed that mammographic screening can reduce the mortality from breast cancer. There are other options as well. This includes ultrasound and magnetic resonance imaging (or MRI) to name a few and these methods are used for specific reasons. For example, MRI can be useful for further evaluation of questionable lesions or for the detection of small lesions.

A review of the level of evidence in support of breast cancer screening methods such as mammography, clinical breast examination and breast self-examination which include the benefits and harms can be viewed at Breast Cancer Screening (PDQ): Summary of Evidence at:
www.cancer.gov/cancertopics/pdq/screening/breast/healthprofessional

To learn more about mammography view Learn About Mammograms at:
www.cancer.gov/cancertopics/screening/breast/mammogram

3. How does age alter the risk for breast cancer?

Cancer cells exhibit properties of abnormal cell growth. Evidence suggests that breast cancer (as all cancers) arises through an accumulation of mutations in genes that play a role in controlling cell growth. Mutations usually arise in a random way. They usually occur during cell division as a consequence of DNA replication (DNA being the building blocks of genes) as all daughter cells arising from cell division must have a complement of DNA from the original parental cell. Cell division occurs to replenish cells of various organs. So only actively dividing cells are prone to accumulating mutations. Mutations can be corrected in cells as there are mechanisms in place to fix errors that occur during DNA replication as a consequence of cell division. Sometimes these mutations are not corrected by these DNA repair mechanisms. If the mutation occurs in genes which are critical for controlling cell growth then it is possible that a cell begins to replicate itself abnormally leading to the developing of a tumour which may then through the accumulation of additional mutations giving rise to a malignancy (or cancer). It is estimated that at least one mutation could occur in one million cells per cell division. There are at least 32,000 genes in each human cell (or genome). Only a few of these genes are critical for controlling cell growth (division). Only specific mutations within genes are deleterious or capable of causing an alteration in the proteins that they are responsible for producing. The length of time it takes to for all of these events to occur accounts for why most cancers occur in adults and at an advanced age. There are however some cancers where few specific mutations are required to develop the disease, such as leukemia. However, most ‘solid’ cancers such cancers of breast, colon and lung are known to require a number the accumulation of a number of mutations in key genes.

The age of diagnosis of breast cancer (and some other adult onset cancers) can however occur at a younger age than average in some individuals. This is due to the inheritance of high risk genes which modify risk to such an extent that it not only increases the chance of developing cancer but increases the chance of developing the disease at a younger age than those who have not inherited a high risk breast cancer susceptibility gene (a subject of the Mini Med). For breast cancer to develop under these circumstances, an accumulation of mutations in key genes which control cell growth must occur as described above (sometimes the same genes are involved). However, the time-line for development is at a younger age. Carriers of high risk genes develop cancer at a younger age than average because they carry a mutation in genes which are thought to affect the integrity of the human genome. Once a random mutation occurs in the normal gene the cells are prone to accumulating mutations at a rate faster than normal. If they occur in key genes then cancers can arise. The accumulation of these additional mutations in key genes controlling cell growth occurs randomly and thus may account for variability in age at diagnosis in carriers of high risk genes. This also explains why not all carriers of high risk genes develop breast cancer even if they live to age 80.

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