Inset: A family photo taken circa 1948 includes the four aunts and two cousins of Sheila Saxe who were diagnosed and died at an early age from cancer.

As a teenager in the 1960s, Sheila Saxe was jolted by the death of four aunts, one after the other.

“Within six years, four women in my grandfather’s family died: two of ovarian cancer, one of breast cancer and one of an unknown cancer,” she says.

“I thought, gosh, did they catch it from each other? Was the family cursed?”

Cancer moved into the next two generations. It skipped her mother, but touched her mother’s cousin. Then her own cousin was diagnosed with breast cancer at the age of 28.

Finally, in her 50’s, through testing at the UConn Health Center, Saxe learned that her family did have a higher cancer risk—one caused by genetic code.

She carried a mutation in one of the breast cancer suppression genes (BRCA) that can greatly increase the risk for developing breast and ovarian cancer at an early age and can be passed to children, thereby increasing their risk for developing the disease.

“Frankly, it was a relief,” says Saxe, who, with the test results, received guidance about its implications from Robin Schwartz, a genetic counselor at UConn’s Division of Human Genetics.

Saxe promptly had surgery to remove her ovaries. While the operation uncovered no obvious signs of disease, a subsequent pathology exam showed cancerous tumors on both ovaries.

“So I had a complete hysterectomy and chemotherapy. Tests now show me to be cancer free and I have follow-up exams every three months. My cousin lived only 15 months after diagnosis. I am very lucky,” says Saxe.

Saxe is one beneficiary of the advances in molecular biology that have vastly expanded our knowledge about human genetics and disease.

Peter Benn, professor of genetics and developmental biology and director of the human genetics laboratory.

Photo by Lanny Nagler

“It was only about 50 years ago that we figured out the precise number of chromosomes in a cell, which opened the door to identifying chromosomal abnormalities,” says Peter Benn, professor of genetics and developmental biology and director of the human genetics laboratory.

Some major chromosomal abnormalities, such as missing or an extra chromosome, can be detected under a microscope to diagnose disorders like Down syndrome.

Other inherited disorders, such as sickle cell anemia or cystic fibrosis, are the result of single gene abnormalities that can be found only with more sophisticated molecular analysis; while still other diseases, such as diabetes, have been linked to multiple genes.

And, more recently, scientists have begun to learn that environmental factors like chemical exposure, diet and other lifestyle differences can affect the function of genes and their contribution to certain diseases.

“We can help individuals and families understand their risk of many diseases and often we can offer them counseling and tools to help manage that risk,” says Robert Greenstein, director of the Division of Human Genetics.

For Holly and Kevin Potter, counseling led them to specialized genetic testing that helped them start a family. Kevin has cystic fibrosis, an inherited chronic disease that affects the lungs and digestive system.

The Potters worried about passing the disease to their children. “We discussed adoption, but we thought we would like to have our own children,” says Holly.

Because her husband had the disease, Holly underwent testing to determine her status. “I found out that I also was a carrier for cystic fibrosis.” When both parents carry the gene, there is a greater chance of passing the disease to their child.

Kevin and Holly Potter, both cystic fibrosis carriers, turned to the Center for Advanced Reproductive Services at UConn’s Health Center for help with genetic diagnosis prior to in vitro fertilization. Their son Aiden was born free of the disease.

For help, the Potters turned to the Center for Advanced Reproductive Services at the UConn Health Center for pre-implantation genetic diagnosis (PGD), a test used during in vitro fertilization to identify embryos with genetic disorders.

The test makes it possible to transfer only those embryos without the disorder into the woman’s uterus.

“Without this testing, we wouldn’t have dared to have children,” says Holly. Their son, Aidan, was born without cystic fibrosis, though they learned he too is a carrier.

“My husband is very lucky he has a mild case of cystic fibrosis, but it is not something you want to pass along to your children. The doctors told us that PGD reduces the chances of having a child with the disease to about 5 percent. Still we were on pins and needles until we got the results of Aidan’s test.”

Genetic testing on newborns is another significant milestone for treating disease. In the 1960s, genetic testing was introduced for babies born in hospitals to identify phenylketonuria, a metabolic disorder resulting in metal retardation that can be effectively treated by early diet therapy.

Since then, the number of disorders for which newborns are tested has increased steadily in most states.

In Connecticut, more than 40,000 babies are screened annually for hearing loss and for more than 40 genetic or metabolic disorders within days of birth, says Greenstein.

The Division of Human Genetics is a designated treatment and management center for babies with disorders detected by the screening program. About 2,100 screened babies, or 5 percent, will have a positive result that requires more testing.

“Our ability to develop screening tests for inherited diseases and metabolic errors has been extremely useful,” says Benn, who with colleagues in the Department of Obstetrics & Gynecology published their research.

The study, which appeared in the Journal of Obstetrics & Gynecology, concluded that noninvasive screening procedures like blood tests and ultrasound for pregnant women can detect fetal chromosomal abnormalities such as Down syndrome and neural tube defects almost as effectively as more invasive procedures such as amniocentesis — the removal of amniotic fluid — which have a higher risk of miscarriage.

“Either you get a negative result, which can provide considerable reassurance, or you get a positive result and obtain additional diagnostic tests.”

Traditionally, according to Benn, there has been a consensus among scientists and physicians that genetic screening should be offered only for conditions for which there is an available intervention or therapy.

However, research is causing a change in such thinking.

“We are now at a point where we can test for many more disorders than we can effectively treat,” says Benn, who cautions that the screening tests don’t come without a cost.

“It’s not just the economic price, which can be considerable, but the cost of false positive results, which can increase stress and emotional suffering. Screening tests are introduced when the benefits are considered to outweigh these disadvantages.”

Screening and genetic diagnosis for some disorders may be appropriate for some families and not others. For example, it would be reasonable to consider genetic testing for breast and ovarian cancer for a woman with a family history of the disease, but not necessarily for all women.

And, says genetics counselor Jennifer Stroop, not all cancer is hereditary. Breast cancer, for example, is diagnosed in 200,000 American women every year, but hereditary breast cancer is rare, accounting for only about 5 to 10 percent of the cases.

“If the cancer is hereditary, that information can empower people,” says Stroop, who meets with patients to interpret the test results and discuss the implications for them and family members.

Stroop tells of one woman who was diagnosed with breast and then ovarian cancer. She had genetic testing before she died because of concerns about her two daughters. When the daughters were tested, they learned they didn’t have the altered gene.

“In some ways,” says Stroop, “the information becomes a gift.”