Red flags for hereditary cancers

Carcinogenic agents induce cancer by causing genetic mutations that allow cells to escape normal biological controls. Most cancers begin this way, sporadically in an individual, and may involve several mutations that permit a tumour to grow. But sometimes, a single, potent, cancer-causing mutation is inherited and can be passed from one generation to the next. An estimated 5 to 10 per cent of cancers are strongly hereditary, and 20 to 30 per cent are more weakly hereditary, said Dr Kenneth Offit, chief of clinical genetics at Memorial Sloan-Kettering Cancer Center in New York.

Genetic Chances

In hereditary cancer, the mutated gene can be transmitted through the egg or sperm to children, with each child facing a 50 per cent chance of inheriting the defective gene if one parent carries it and a 75 per cent chance if both parents carry the same defect.

You may be familiar with the BRCA1 and BRCA2 mutations that are strongly linked to breast and ovarian cancer in women and somewhat less strongly to breast and prostate cancer in men. A woman with a BRCA mutation faces a 56 to 87 per cent chance of contracting breast cancer and a 10 to 40 per cent chance of ovarian cancer.

For some hereditary cancer genes, the risks are even greater. A child who inherits a so-called RET mutation, faces a 100 per cent chance of developing an especially lethal form of thyroid cancer. Likewise, the risk of stomach cancer approaches 100 per cent in those with a CDH mutation, Dr Daniel G Coit, a surgeon at Memorial Sloan-Kettering, said at a recent meeting there.

Megan Harlan, senior genetic counsellor at Sloan-Kettering, said these were red flags that suggest a cancer might be hereditary:

8226; Diagnosis of cancer at a significantly younger age than it ordinarily occurs.

8226; Occurrence of the same cancer in more than one generation of a family.

8226; Occurrence of two or more cancers in the same patient or blood relatives.

For example, a woman with a BRCA mutation is at high risk for both breast and ovarian cancer. A mismatch repair mutation, known as MMR, significantly raises the risk for colon cancer and somewhat for uterine and ovarian cancer. Thus, the occurrence of colon, uterine and ovarian cancers among blood relatives suggests that the family may carry the MMR mutation.

Preventive Actions

Knowing that you have a high-risk cancer gene mutation offers the chance to take preventive actions like scheduling frequent screenings starting at a young age or removing the organ at risk.

While surgery is clearly a drastic form of cancer prevention, in the future, drugs may be able to thwart cancers in people at high risk, Dr Offit said. A third possibility, when a cancer gene runs in a family, is in-vitro fertilisation and genetic analysis to identify affected embryos and implant those lacking the defective gene.

Harlan suggested that a woman with a BRCA mutation should start at an early age to conduct monthly breast self-exams and have a doctor examine the breasts two to four times a year. She also advised alternating mammograms and breast MRI8217;s every 6 to 12 months, starting at age 25.

Likewise, someone who carries an inherited colon cancer gene should start yearly colonoscopies at 20 or 25. A woman with a uterine cancer gene mutation should be screened with sonography and endometrial biopsies yearly and, Offit added, consider having her uterus removed when she has finished having children.

A growing number of women with BRCA mutations are choosing prophylactic mastectomies and, in some cases, oophorectomies, or removal of the ovaries. That reduces their risk of breast or ovarian cancer by 75 per cent.

Coit described a family in which the father and his father both developed thyroid cancer linked to the RET mutation. The younger man8217;s 6-year-old son was tested and found to carry the same damaged gene. Because the boy was certain to develop thyroid cancer, most likely at a young age, his thyroid was removed. Although the boy will need to take thyroid hormone for the rest of his life, the surgery reduced to zero his chance of developing this often fatal cancer.

Coit also told of a 33-year-old woman who carried the CDH mutation associated with highly lethal stomach cancer. Her stomach was removed and found to contain three microscopic cancer sites, making her preventive surgery also curative. She is one of 131 patients with the mutation who have had their stomachs removed and a stomach-like pouch created from the small intestine. The doctor acknowledged that the surgery was a drastic measure, with an operative mortality of 1.5 per cent and a complication rate of 53 per cent. Most patients cannot eat as much as they used to after the surgery. They develop food intolerances and lose weight, but they do eventually adapt to their new digestive system, Coit said.

Practical Considerations

Before choosing surgery to reduce risk in an otherwise healthy person, Coit said these factors should be carefully considered:

8226; Possible nonsurgical alternatives

8226; Actual cancer risk from the inherited gene and how much surgery can reduce it

8226; Timing of any operation

8226; Effects of surgery on quality of life

The deciphering of the human genome has prompted a number of entrepreneurs to cash in on people8217;s genetic concerns. They offer DNA testing to look for aberrant genes associated with the risk of developing various diseases, especially cancer. Such testing, when done reliably, might encourage some people to take charge of their health and make better plans for the future. But some professional genetics counsellors say this approach to determining cancer risk is fraught with hazards, not the least of which is a false warning of a serious risk that does not exist.

8220;This kind of testing is premature,8221; said Kenneth Offit, chief of clinical genetics at Memorial Sloan-Kettering Cancer Center.

8220;Some companies are selling research tests for mutations that carry a low risk of causing cancer, leading people to worry needlessly or be falsely reassured.8221;