Although we note that cancer is a complex and challenging disease that has been attacked on many research fronts, we must also be aware that there is a human side to dealing with cancer.

In the late 1980s and early 1990s, the genetic basis for cancer-predisposition syndromes rapidly unravelled with the discovery of a number of tumour-suppressor genes that were found to be inherited in mutant form in affected families. These included genes associated with the childhood cancer Wilms' tumour, Li Fraumeni syndrome, neurofibromatosis, familial adenomatous polyposis, von Hippel-Landau disease and retinoblastoma (see Milestone 11). Many of these genes are now known to have key roles in cell proliferation, cell-cycle checkpoints and cell death (see Milestone 20).

At the same time, researchers were frantically searching for, and finding, more susceptibility genes and molecular mechanisms, so that genetic counsellors and patient-care professionals around the world could begin translating these important advances into real-world advice for patients who were forced to make profound decisions. The discovery of inherited mutations leading to more common diseases, such as breast cancer and colon cancer, serves to illustrate this point.

Before 1990, we knew that 5–10% of breast and colon cancers occurred in familial patterns, but whether these were owing to shared environments, several interacting genes or single major genes was not known. A breakthrough came with the identification of genes on chromosomes 2 and 17 that were associated with major fractions of colon and breast cancers, respectively. These, and related genes discovered shortly thereafter, were MSH2 and MLH1 in hereditary non-polyposis colorectal cancer, and BRCA1 and BRCA2 in hereditary breast cancer syndromes. Interestingly, in both types of hereditary cancer, as well as in other cancer-predisposition disorders, the predisposing genes affect DNA repair rather than cell growth per se (see Milestone 22).

The penetrance of mutations varies in families, and most breast and colon cancers do not appear to be of hereditary origin. Yet, for families dealing with these cancers, the identification of the genes meant that testing was possible, and difficult prophylactic-care decisions could be informed by the test results.

In the decade since their discovery, testing for cancers resulting from mutations in cancer-susceptibility genes has become more common. However, the decision to be tested and knowing what to do with the information have not necessarily become any easier. For example, prenatal testing is now available for conditions such as neurofibromatosis, which is a common hereditary disease that leads to numerous benign tumours throughout the body.

Unfortunately, like MSH2 and BRCA1, the neurofibromatosis gene NF1 is large and subject to a range of mutations, so testing is difficult unless a specific mutation has been identified in another family member. Moreover, as in hereditary breast and colon cancer syndromes, the chance of developing tumours and their severity varies greatly, even when a mutation is found. Basic cancer research must therefore lead directly to the translation of important findings into information for patients. The advent of the Internet has greatly assisted this process, and websites such as that of the National Cancer Institute in the United States are consulted by thousands of patients and their family members each day.