Genetic Testing – Does it Detect Cancer?

The term “genetic testing” used in this article encompasses all tests and methods thought to identify cancer or the predisposition for cancer via analyzing DNA or RNA of an organism. It can be further divided in two general groups – tests that screen host (human) DNA for mutations (genetic testing) and tests that identify the presence of parasite DNA (bacterial or viral).
One of the most useful examples of a genetic test is one that screens for parasite DNA associated with human papillomavirus (HPV). Scientific research showed that persistent HPV infections could be one of the causes of cervical cancer. In 2007, it was estimated that 11,000 women in the United States would be diagnosed with this type of cancer and nearly 4,000 would die from it. Cervical cancer affects nearly half a million women each year worldwide, claiming a quarter of a million lives. Studies also suggest that HPVs may play a role in some cancers of the anus, vulva, vagina, and penile cancer (cancer of the penis) (1). In addition, studies have found that oral HPV infection could be a risk factor for oropharyngeal cancer (cancer that forms in the middle part of the throat and includes the soft palate, the base of the tongue, and the tonsils) (1,2).
Some types of HPV are referred to as “low-risk” viruses because they rarely cause lesions that develop into cancer. HPV types that are more likely to lead to the development of cancer are referred to as “high-risk.” Both high-risk and low-risk types of HPV can cause the growth of abnormal cells, but only the high-risk types of HPV can lead to cancer. Sexually transmitted, high-risk HPVs include types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, and 73 (3). HPV types 16 and 18 together accompany about 70 percent of cervical cancers (3, 4).
It is important to note, though, that presence of HPV only signals of the increased risk of developing cancer, it does not detect cancer cells. The great majority of high risk HPV infections go away on their own without causing any type of abnormality. Even among the women who do develop abnormal cell changes with high-risk types of HPV, only a small percentage would develop cervical cancer if the abnormal cells were not removed. Studies suggest that whether a woman develops cervical cancer depends on a variety of factors acting together with high-risk HPVs (5). The factors that may increase the risk of cervical cancer in women with HPV infection include smoking and having many children (5).
Genetic testing is a process that looks for inherited genetic alterations that may increase the risk of certain cancers. This type of testing may show whether the risk in a family is passed through their genes. There is evidence that some kinds of cancer, such as breast and ovarian cancer, seem to run in families.
A genetic test for breast and ovarian cancer risk will not yield a simple "yes" or "no" answer. If a gene alteration is found, this will indicate that a person has an increased risk of getting cancer, but it will not tell if or when cancer will develop. If an alteration is not found, it still is no guarantee that cancer won't develop.
In recent years, several gene mutations have been discovered that were thought to increase a woman's risk of breast cancer. These alterations are most often found in genes named BRCA1 and BRCA2 (BReast CAncer Gene 1 and BReast CAncer Gene 2). Both men and women have BRCA1 and BRCA2 genes, so alterations in these genes can be passed down from either the mother or the father.
A woman with a BRCA1 or BRCA2 alteration were thought to be at higher risk for developing breast, ovarian, and other cancers than a woman without an alteration. However, not every woman who has an altered BRCA1 or BRCA2 gene will get cancer, because genes are not the only factor that affects cancer risk.
A positive test result generally indicates that a person has inherited a known harmful mutation in BRCA1 or BRCA2 and, therefore, thought to have an increased risk of developing certain cancers. However, a positive test result provides information only about a person’s risk of developing cancer. It cannot tell whether an individual will actually develop cancer or when.
Moreover, a recent report (6) published by scientists from the U.S. National Cancer Institute (NCI) suggests that DNA doesn't predict breast cancer risk much better than a questionnaire.
In theory, testing for BRCA1 or BRCA2 could allow women to make more informed choices about how often to undergo routine mammograms, for example, or, more radically, whether to take anticancer drugs like tamoxifen prophylactically. These decisions are currently made by patients, in consultation with clinicians, based on a predicted risk of cancer provided by the so-called Gail model. This model calculates a risk based on the answers to seven questions, including the age at which a woman began menstruating, the age at which she had her first child, and the number of relatives with breast cancer (6, 7)
To find out how well genetic screening measured up to the question-based Gail model, researchers pooled data from five of the studies originally used to identify the breast cancer genetic risk factors. Then they retrospectively calculated a prediction of cancer risk based on each woman's data for the 10 genetic risk factors known at the outset of the study.
They asked a very simple question: “what is the probability that a woman selected at random from the group that did go on to develop cancer would have a higher risk prediction than a randomly selected woman who did not?” For a completely useless model, the answer would be 50%; for a perfect model, the answer would be 100%. The answer for the genetic screening was 59.7%, whereas the answer for the question-based Gail model was 58%. By combining the two, the researchers were able to produce a model with a predictive power of 61.8%. But that combination didn't impact the prediction of risk, also called the score, very much for most individual patients (6, 7). Cancer epidemiologist Dr. Pharoah, who published a similar report in 2008 in New England Journal of Medicine based on just seven genetic risk factors, came to the same conclusion that genetic tests don't add a whole lot to the Gail model (8).
A recent study from Roche’s biotechnology unit in California discovered 50,000 genetic mutations associated with lung cancer (9). It is suggested that the number of genetic mutations correlates with the number of cigarettes smoked, and in this specific case smoking 3 cigarettes is associated with 1 genetic mutation. This type of analysis required costly whole genome sequencing, and provides an example of the impractical uses of genetic testing for identifying disease. With over 50,000 genetic mutations to choose from, it will be difficult for the medical to rely on this evidence.

References:
1. Parkin DM. The global health burden of infection-associated cancers in the year 2002. International Journal of Cancer 2006; 118:3030–3044.
2. D'Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal cancer. New England Journal of Medicine 2007; 356:1944–1956.
3. Munoz N, Bosch FX, Castellsague X, et al. Against which human papillomavirus types shall we vaccinate and screen? The international perspective. International Journal of Cancer 2004;111:278–285.
4. Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S. Human papillomavirus and cervical cancer. The Lancet 2007; 370:890–907.
5. National Cancer Institute. Future directions in epidemiologic and preventive research on human papillomaviruses and cancer. Proceedings of a workshop. Bethesda, Maryland, June 2002. Journal of the National Cancer Institute Monographs 2003; 31:1–130.
6. Wacholder, S. et al, “Performance of common genetic variants in breast-cancer risk models”, New England Journal of Medicine, 362, 11, 986-983, 2010.
7. Wogan T. “Genetic Testing for Cancer Risk Not Clinically Useful”, ScienceNOW, March 17, 2010
8. Pharoah PDP, Antoniou AC, Easton DF, Ponder BAJ “Polygenes, Risk Prediction, and Targeted Prevention of Breast Cancer”, New England Journal of Medicine, 358, 2796, June 26, 2008
9. Steenhuysen, J. “U.S. gene study reveals toll of heavy smoking”, Reuters May 26, 2010. http://www.reuters.com/article/idUSTRE64P62Z20100526