individual risk. In this way, relatives who carry the familial mutation
can take appropriate risk-reducing measures, while those without
the mutation can avoid unnecessary and costly medical procedures.
For the broader population, researchers have devised models to
predict the likelihood that a person will develop certain cancers, with
the goal of selecting those who may benefit from additional
screening (see Sidebar on Modeling Cancer Risk, p. 41). These
models are based on known risk factors, but are imperfect. The Gail
and Claus models for determining a woman’s risk for breast cancer
are the most used commonly used in the clinic ( 54, 55). Further
research to develop models that not only more accurately quantify
risk, but also estimate the benefits of modifying risk factors (e.g.,
through reducing alcohol consumption) is urgently needed if we
are to target preventive interventions to the people who would
Many researchers are seeking to identify biomarkers that could be
used to stratify an individual’s cancer risk—for example,
biomarkers signifying exposure to a cancer-causing agent (see Fig.
5, p 23). Ideally these biomarkers would be measurable in small
amounts of accessible material such as blood, urine or saliva.
Current research in this area aims to harness recent technical
advances and powerful analytical platforms to discover such
Clearly, stratifying risk is important for reducing the morbidity and
mortality of cancer in high-risk individuals, but it also has the
benefit of decreasing the complications and cost of unnecessary
health care interventions for those at low risk for disease. Every
medical procedure, even a seemingly harmless approach for
screening for early detection of certain cancers, carries with it
some risk for an adverse effect. Eliminating the need for low-risk
individuals to be exposed to these procedures also reduces health
care costs, providing additional impetus to expand our research
efforts to develop new, accurate and reliable ways to discern an
individual’s cancer risk.
Figure 14: Small Genetic Steps for Cells Lead to a Giant Leap for Cancer. Many cancers are progressive in nature, particularly non-blood
cancers, such as those that arise in the lining of many organs. An initial genetic change can lead to a change in the tissue, for example the
formation of a small adenomatous polyp in the lining of the colon. Over time, further genetic alterations in a cell within the polyp leads to a more
advanced precancerous lesion. Given more time, additional genetic mutations are acquired, leading to increasing levels of what is called
dysplasia, or changes in cell shape. Ultimately, as the genetic changes accumulate and cause further cellular changes, the dysplastic
precancerous lesions may evolve into cancerous lesions within the tissue. As yet more mutations arise, the cancer cells gain the ability to
metastasize, which they do by entering into nearby blood and lymphatic vessels. Routine screening using the Pap test and colonoscopy aims to
detect early-stage precancerous lesions so that they can be removed before they have the chance to grow and metastasize.