Meditations of an oncology geek

Is cancer a genetic disease?

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This week’s article was inspired by Christy Wheeler from San Diego, CA

Cancer is a genetic disease, but is not genetically heritable (most of the time).

Image: Though rare, genetically heritable gene variants can cause cancer to run in families. In these instances, cancer often presents at a much younger age than normal, often in the same or related tissues, and consistently shows up in multiple generations. An example is this family that has a mutation in the BRCA1 gene. Breast and ovarian cancer cases presented in their 30′s and 40′s, as opposed to 60′s or 70′s, which is the norm. Image from Barry et al. 1995, which developed mathematical models to predict cancer risk among such families. Squares represent males, circles represent females. BC = breast cancer. OC = ovarian cancer.

The term “genetic” often carries a morbid sense of determinism. People often conflate “genetic” the term “genetically heritable.” The former implies anything that is a result of instructions written in DNA. The latter is used to describe anything that is written in DNA and can be passed from one generation to the next.

The changes at the cellular level that cause cancer cells to grow, spread, and resist death are borne in their DNA. Non-pathological “normal” cells mutate, which eventually leads to tumors, and although the exact type and timescale of mutations varies by the specific type of cancer, the underlying theme is a permanent change in the DNA blueprints of the cell. This is accomplished by exposure to carcinogens, as explained in a previous article. This change in the cell’s DNA blueprint carries pathological consequences, which explains how cancer is genetic. At the root of cancer are changes in DNA.

For example, let’s say Jane goes on a trip with her family when she is a little girl and winds up getting a very bad sunburn. At age 25, she goes in to the doctor for a regular checkup and the doctor spots a funny-looking mole on her back. Being a cautious physician, she removes the mole and sends it off to be evaluated by a pathologist. The pathologist identifies it as melanoma in its early stages. Jane goes in for follow-up therapy, and after five years has no remissions. Jane is a cancer survivor.

Eight years later, Jane gets married and starts a family. Although she had melanoma as a child, the DNA she passes on to her children give them no greater chance of developing melanoma than she did. Why?

The vast majority of the time, cancer is a disease of somatic tissue. Most of your body is considered somatic tissue, but the exception is a very special subset of cells that are called the germ cells. Germ cells create eggs in women and sperm in men: at birth, you will have all the germ cells present that you will have the rest of your life. Early in fetal development, the cells that will form the germ cells are partitioned away and protected. These cells do not go through nearly as many rounds of replication as somatic cells, which make up the rest of the body – this is an ancient evolutionary trick that prevents excessive replication of the germ line and wards off genetic mutations.

There are certain variants of genes that run in families that can confer an increased risk of developing cancer. For instance, there are families with mutations in the BRCA1 and BRCA2 genes that confer a greater chance of developing breast and ovarian cancer. Jane’s cancer, in the example above, was sporadic as opposed to familial. The key mutations that led to her disease were caused by external biological insults – in this case, UV radiation. Familial cancers are the exception rather than the rule: for instance, it is estimated that only 5-10% of breast cancer is familial (1), while the remainder is sporadic.

Most of the common cancers in the U.S. are predominantly sporadic in cause: skin cancer, lung cancer, breast cancer, and prostate cancer.

So, maybe two of your grandparents died of cancer, and your uncle was recently diagnosed? Does this mean cancer runs in your family? Well, it depends. There are a few things that cancers arising from familial inherited risk have in common:

1) The type of cancer tends to manifest at younger ages, usually from the age of thirty to forty in the case of breast cancer, as opposed to the normal age range of seventy to eighty.
2) The type of cancer consistently arises in the same tissue or related organ systems (ovaries vs. breast for example)
3) Multiple blood relatives in the family develop a type of cancer that meets one or both of the previous criteria, usually over multiple generations.
4) There are no obvious environmental influences that could increase the risk of cancer, such as living near toxic waste, or spending a lot of time in the sun.

If you are concerned about your genetic risk of developing cancer, you should contact a genetic counselor. Genetic counselors are professionals that specialize in determining risk for genetically heritable diseases – an example is the Cancer Genetics unit at the Moores Cancer Center at UC San Diego. Often, those with increased risk will begin annual screening at a younger age, and receive information for activities that can help mitigate their cancer risk. At the very least, contacting a counselor will ease the mind.

So there you have it – cancer is a genetic disease, but the vast majority of the time it is not hardwired into your DNA, or, at least, not into all of the healthy cells in your body.

Please feel free to email me with questions!

-Ryon

References:
1) Madigan MP, Ziegler RG, Benichou J, Byrne C, Hoover RN (November 1995). “Proportion of breast cancer cases in the United States explained by well-established risk factors”. Journal of the National Cancer Institute 87 (22): 1681–5. doi:10.1093/jnci/87.22.1681. PMID 7473816.

Written by Ryon

March 6th, 2011 at 4:05 pm

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