spotlight with Kavita Sarin, MD, PhD

The Stanford Skin Cancer Genetics Clinic, the Sarin Lab, and ways for patients to reduce risk of melanoma 

Dr. Kavita Sarin, Associate Professor of Dermatology, directs the Stanford Skin Cancer Genetics Clinic, which provides skin cancer screening, prevention counseling and genetic evaluation for patients with an inherited risk of skin cancer. Outside of the clinic, Dr. Sarin and her lab members apply next generation sequencing technologies to study skin cancer risk, skin cancer progression and response to treatment. In this issue, I spoke with Dr. Sarin about her research, the clinical applications of her work and ways for patients to reduce risk of melanoma.

How is the Kavita Sarin Lab applying cutting edge technologies to understand melanoma risk factors and therapies?

In the Stanford Skin Cancer Genetics clinic, we employ genetic testing to identify patients who are at high inherited risk for developing melanoma and other cancers. These patients are referred to us for evaluation and genetic counseling based on family and personal history of melanoma and other cancers. We offer genetic testing for known genes associated with melanoma risk and other cancers. If we identify a mutation in a melanoma risk gene, we provide appropriate counseling and clinical care in collaboration with our colleagues in Cancer Genetics, Melanoma and Oncology. This information can help guide prevention, screening, family testing and even treatment options for our patients.

However, many patients with an inherited risk of melanoma do not have mutations in known melanoma risk genes. In fact, only about half of the genes known to cause increased melanoma risk have been identified. Our goal is to establish new risk genes for melanoma. We enroll individuals who have developed frequent melanoma and perform whole genome sequencing to see if we can pinpoint genetic mutations that might explain why they or their family members are at increased cancer risk. These findings potentially can be incorporated into clinical genetic testing in the future and help to understand the signaling pathways involved in melanoma risk, which may help us develop therapeutic targets to prevent or treat melanoma.

Our patients are usually referred to us by through the Stanford Pigmented Lesion and Melanoma and Clinic, Stanford Cancer Genetics, Stanford Dermatology Clinics, community dermatologists, or through the Wipe Out Melanoma - California registry, from which many of our datasets are derived. Patients involved in the gene sequencing part of the studies don’t need insurance since this is covered by grants. However, they need to have had three or more invasive melanomas of the skin.

We are learning that when you have a cancer susceptibility, it's often not a predisposition to just one cancer. Numerous cancer risk genes cause increased risk of multiple cancers. And, many of our patients often require management by a multidisciplinary group of physicians to help with early detection and prevention of the cancers for which they are at risk.

Has the Stanford Skin Cancer Genetics Clinic experienced any research breakthroughs, and how are these being used to improve prevention, management, and treatment of melanoma? 

Our cohort consists of over 100 patients with three or more melanomas (range 3-17) and is one of the largest cohorts of multiple melanoma patients.

We have learned that many individuals with multiple melanomas are at extremely high risk of  developing a subsequent melanoma and may have an increased risk of developing internal organ cancers.  As a result of our findings, we recommend cancer screening vigilance in all participants with multiple melanoma, not just the patients with mutations in melanoma risk genes. Second, we recommend lifelong frequent skin cancer monitoring, as we have found that our multiple melanoma patients are at high risk of developing additional melanomas throughout their life.

Furthermore, we have identified new genetic mutations that are enriched in our cohort. And, we are exploring how these might contribute to cancer susceptibility. To achieve this, we're doing functional characterization studies using bioinformatics as well as in the lab, where we transfect these mutations into melanoma cell lines to see how the mutations might influence cancer risk. The overall goal of this study is to identify new melanoma risk genes that we can include in diagnostic clinical testing in the future.

How can patients be proactive in secondary prevention of melanoma as well as advocate for prevention in their loved ones? 

There's a thought that melanoma is primarily caused by sun exposure. While ultraviolet radiation from sunlight increases risk of melanoma, it is important for patients to consider their inherited risk when they gauge their melanoma risk. Some of this is visible, such as the color of their skin or hair and how easily they sunburn. Other risk factors include family history of melanoma and other cancers.

There are three things to consider in melanoma risk.

• Environmental exposure: Environmental exposures may include ultraviolet light, ionizing radiation, and chemical carcinogens. Any of these exposures can increase our cancer risk.

• Genetics: Our baseline genetics significantly increase or decrease our cancer risk. The way we advise patients depends on their baseline cancer risk. As an example, someone who has a germline p53 gene mutation has a high lifetime risk of developing cancer, and we follow these individuals very closely.  One way to describe our practice is 'precision medicine'.  We tailor our prevention or screening based on someone's underlying risk factors, which is both genetic and environmental.

• Skin color: Persons with lighter skin  complexion are at higher risk for melanoma than those with darker skin tones. However, we still need to educate people with darker skin on melanoma risk because melanoma is often diagnosed later, and melanoma that develops in persons with darker skin can have poorer outcomes. This is compounded if they carry a mutation in a melanoma risk gene that further increases their risk of developing melanoma.

The best way for patients to be more proactive in secondary melanoma prevention and advocate for that in their loved ones is to understand melanoma risk factors and respond accordingly. Patients should consider whether they have an unusually high number of family members with melanoma and/or other cancers or if they themselves have had multiple cancers. And, if it is unusually high, they should talk to their primary care physician or dermatologist about genetic screening. High-risk patients can be managed by reducing environmental exposure through regular photoprotection practices including application of sunscreen and wearing protective clothing, doing regular skin checks, and, when needed, getting genetic testing.

What would you like readers to take away from this interview?

Your risk of developing melanoma is influenced by your genetics, family history, skin pigmentation and environmental exposures. If you have an unusually high risk of melanoma (multiple family members with invasive melanoma or other cancers) or have had multiple cancers yourself, please share this information with your doctors. You may benefit from genetic testing.

Knowing your risk early, especially if you carry genetic mutations that increase melanoma risk, may open the door to early screening and prevention opportunities for melanoma and other cancers.

ELLEN DINUCCI is a contributing writer of WOM-California Gazette and staff member of the Office of Cancer Health Equity at Stanford Cancer Institute.