High Number of Certain Skin Cancers Linked to Increased Risk of Breast Cancer

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People who are diagnosed with a higher-than-average number of basal cell carcinomas, a common type of skin cancer, have a higher risk of other cancers, including breast, colon, and prostate cancer, according to a study.

The researchers believe this increase in risk is likely caused by mutations in genes that are responsible for repairing DNA damage.

The research was published online on Aug. 9, 2018 by the journal JCI Insight. Read "Frequent basal cell cancer development is a clinical marker for inherited cancer susceptibility."

Basal cell carcinoma begins in the basal cells, a type of skin cell that produces new cells as old cells die. Basal cell carcinoma appears most often on areas of your skin that are exposed to the sun, such as your head and neck. Basal cell carcinomas are common -- more than 3 million cases a year are diagnosed in the United States alone -- and usually highly treatable.

The skin is the largest organ of your body and is the most vulnerable to DNA damage caused by the sun’s ultraviolet rays. So, researchers wondered if the skin’s susceptibility to cancer could offer clues about a person’s overall likelihood of developing other cancers.

How DNA changes can lead to cancer

Genes are short segments of DNA (deoxyribonucleic acid) found in chromosomes. DNA contains the instructions for building proteins. And proteins control the structure and function of all the cells that make up your body.

Think of your genes as an instruction manual for cell growth and function. Changes or mistakes in the DNA are like typographical errors. They may provide the wrong set of instructions, leading to faulty cell growth or function. In any one person, if there is an error in a gene, that same mistake will appear in all the cells that contain the same gene. This is like having an instruction manual in which all the copies have the same typographical error.

There are two types of DNA changes: those that are inherited and those that happen over time. Inherited DNA changes are passed down from parent to child. Inherited DNA changes are called germ-line alterations or mutations.

DNA changes that happen over the course of a lifetime, as a result of the natural aging process or exposure to chemicals or sunlight in the environment, are called somatic mutations.

Genetic mutations in people with high numbers of skin cancers

To do the study, the researchers looked at 61 people who were treated at Stanford Hospital and Clinics for a higher-than-average number of basal cell carcinomas: an average of 11 diagnoses per person during a 10-year period:

  • about 75% of the people in the study were men
  • the average age was about 69
  • about 97% of the people were of European descent

The researchers collected saliva samples from each person in the study and performed genetic testing to look for mutations in 29 genes that help repair DNA damage. Mutations in these genes are linked to many other types of cancer.

The researchers found that 19.7% of the people in the study had mutations in 12 DNA repair genes, including:

  • APC
  • BARD1
  • BRCA1
  • BRCA2
  • CDH1
  • CHEK2
  • MLH1
  • MSH2
  • MSH6
  • MUTYH
  • NBN
  • PALB2

In comparison, about 3% of people in the average population have mutations in those genes.

"We found that about 20 percent of the people with frequent basal cell carcinomas have a mutation in one of the genes responsible for repairing DNA damage, versus about 3 percent of the general population. That's shockingly high," said Kavita Sarin, M.D., Ph.D., assistant professor of dermatology at Stanford and senior author of the study.

Mutations in the BARD1, BRCA1, BRCA2, CDH1, CHEK2, MSH6, NBN, and PALB2 genes are associated with a higher risk of breast cancer.

When looking at the cancer history of the people in the study, the researchers found that 34.4% had a personal history of another cancer besides basal cell carcinoma, including:

  • invasive melanoma, a type of skin cancer
  • hematologic cancers, such as leukemia, lymphoma, and multiple myeloma
  • breast cancer
  • colon cancer
  • prostate cancer

This is more than 3 times the rate of cancer in the average population of 60- to 69-year-olds.

The researchers noted that more than 85% of people in the United States are 55 or older when first diagnosed with skin cancer. But among the people in the study, the first diagnosis of skin cancer was more than 10 years earlier, at an average age of about 44. They also said that skin cancer developed before the age of 30 for 16.4% of people in the study. In comparison, just 1.3% of the general population develops skin cancer before age 35.

Finally, the researchers looked at a database of medical insurance claims to see if people who were treated for basal cell carcinoma were more likely to also be treated for another type of cancer. Compared to people who had never been diagnosed with basal cell carcinoma, people who had been diagnosed with:

  • one basal cell carcinoma were 1.61 times more likely to be diagnosed with another cancer
  • six or more basal cell carcinomas were 3.12 times more likely to be diagnosed with another cancer
  • 12 or more basal cell carcinomas were 4.15 times more likely to be diagnosed with another cancer

"We discovered that people who develop six or more basal cell carcinomas during a 10-year period are about three times more likely than the general population to develop other, unrelated cancers," Sarin added. "We're hopeful that this finding could be a way to identify people at an increased risk for a life-threatening malignancy before those cancers develop."

Sarin emphasized that people who develop an occasional basal cell carcinoma shouldn’t worry.

"About one in three Caucasians will develop basal cell carcinoma at some point in their lifetime," she said. "That doesn't mean that you have an increased risk of other cancers. If, however, you've been diagnosed with several basal cell carcinomas within a few years, you may want to speak with your doctor about whether you should undergo increased or more intensive cancer screening."

What if you’ve been diagnosed with six or more skin cancers?

While the results of this study are troubling, they also give us more information about who might be at higher risk for breast cancer, which is good to know.

If you’ve been diagnosed with six or more basal cell carcinomas during a 10-year period, you may want to talk to your doctor about whether genetic testing makes sense for you. You also may want to ask if more frequent screening and different types of screening, such as breast MRI and breast ultrasound, makes sense for your unique situation.

In addition to more frequent screening, there are lifestyle choices you can make to keep your risk of breast cancer as low as it can be, including:

  • maintaining a healthy weight
  • exercising every day
  • limiting or avoiding alcohol
  • eating a healthy diet full of fresh, whole foods and avoiding processed foods with a lot of added sugar and salt
  • never smoking (or quitting if you do smoke)
  • breastfeeding, if you have the option to do so

For more information on breast cancer risk factors, including genetics, and additional steps you can take, visit the Breastcancer.org Lower Your Risk pages.

To discuss your risk of breast cancer, and any risk factors you may have, with others, join the Breastcancer.org Discussion Board forum High Risk for Breast Cancer.


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