Over the last five decades, Medical Genetics has evolved from a mostly descriptive discipline into a much more proactive and clinically useful component of healthcare. By far the most innovative and impactful advances have come in Cancer Genetics and Genomics.

Cancer is fundamentally caused by genetic changes that disrupt normal cell behavior and allow uncontrolled cell growth. While all cancer has a genetic basis, 10% of cases are due to genetic variations present at birth (inherited) that led to an increased predisposition to cancer. These are called hereditary cancers. 

The identification of hereditary cancer is often dependent on the availability of a comprehensive family cancer history. Regrettably, this means an individual’s family member, or even the individual themselves, would need a cancer diagnosis before being tested for hereditary cancer. This leads to missed, or delayed screens and it also fails to account for individuals who have a hereditary cancer condition that was not inherited from an affected parent but rather occurred by chance (de novo) during conception.

With Orchid, these limitations are reduced. We no longer are limited by only known mutations that run in families. We are no longer bound by patients’ limited knowledge  of their family history. We no longer even need to wait for an at-risk individual to start cancer screening.

For the first time, cancer genetics can be profoundly proactive: Orchid’s embryo screen identifies abnormalities in ninety plus genes known to predispose individuals to cancer, and identifies embryos at risk of hereditary cancer. This enables patients and their providers the ability to identify and assess risk, and make informed decisions prior to transferring an embryo. 

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Pediatric Hereditary Cancers

Kristina was born in 2003 and just celebrated her 20th birthday. She  was the beautiful product of an uncomplicated pregnancy. Because her father had been diagnosed in his childhood with an eye tumor  called retinoblastoma, Kristina was examined immediately after birth. She was found to have bilateral eye tumors, the right much larger than the left. She began chemotherapy treatment at 10 days old. In the first year of life  Kristina lost her right eye and was fitted with a prosthesis. She was  also found, at 9 months of age, to have a retinoblastoma lesion within her brain. The family was quoted only a 2% chance of survival. Although the challenges were daunting, the family agreed to 9 more rounds of chemotherapy, two bone marrow transplantations, many blood transfusions, and much more chemotherapy. 

Kristina’s sister, Brandy, had a nearly identical story, and she lost an eye as well. I remember her mother saying “We spent almost ten years straight in the hospital.”

Happily, this is a success story: Kristina and Brandy have been cancer free for 18 years. 

They would both like to start their own families, knowing there are significant risks to manage. Orchid can help: if they pursue IVF we can screen their embryos and identify which have inherited their abnormal Rb gene  that predisposed them to their cancer.  These sisters now have a way to reduce retinoblastoma diagnosis risk for their children.

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Adult Hereditary Cancers

A few years ago, Teresa came to me with a question. Her mother, Mary, was my patient and had been diagnosed with ovarian cancer. Testing showed that both Mary and Teresa had the same mutation in the BRCA2 gene. Teresa was ready to start her family and she wanted to avoid passing her BRCA2 mutation on to her family’s next generation. However, she was also aware that many other genes are involved in hereditary cancer risk, some of which are not inherited from a family member. She asked the most appropriate question: might it be possible to use IVF testing to screen for more known genes associated with cancer risk at the same time before the pregnancy begins?

For Teresa, Orchid might be able to help: Orchid’s embryo screen can detect the BRCA2 gene, plus almost 100 others that elevate risk for pediatric and adult cancers. Teresa could select embryos that have a reduced risk for these mutations.

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Conclusion

Our knowledge of cancer genetics is limited, but growing. While we don’t know everything, we do know that mutations in certain genes significantly increase cancer risks. Genetic testing for hereditary cancer is readily available and a commonly used tool for clinicians. Identifying hereditary cancer risk can help patients make important lifestyle and healthcare choices to reduce their risk of developing cancer despite their elevated genetic predisposition for it.

Although there have been advancements in preconception cancer testing, its scope remains limited. For instance, Preimplantation Genetic Testing for Monogenic Disorders (PGT-M) is available for embryos, but only applicable when patients know the specific gene variant they wish to prevent their child from inheriting. This method does not address other problematic genes that may be inherited from parents, nor does it address random gene mutations that occur within the embryo (de novo).

Orchid is different: Orchid’s embryo screening identifies ~100 genes that are known to increase the risk of hereditary cancer for adults and children, regardless of family history. All of this, even before pregnancy begins.

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