By Elianna Miller
Approximately 1,762,450 new cancer cases will be diagnosed in
in 2019. This number has grown rapidly since 2005, but what caused this
increase? Is it people’s DNA, their environment, or is it just bad luck?
A lot of the Sarnoff Center’s work focuses on hereditary
cancers, particularly BRCA mutations, which are 10x more common in Jewish communities
than the general population. BRCA mutations are linked to breast cancer in
women in men, ovarian cancer, prostate cancer, pancreatic cancer, and melanoma.
The average woman’s lifetime chance of a breast cancer diagnosis is about 12%,
but that increases to 45%- 87% with a BRCA mutation. Lynch syndrome is another
inherited genetic disorder that can be linked to Ashkenazi Jewish ancestry,
which increases the likelihood of some gastrointestinal cancers.
If someone with a mutation such as these ends up developing
cancer, it typically happens earlier in life than with the average person.
Cancer predisposition genes are typically present from birth, though the actual
cancer doesn’t form until later. That means there must be more to it than just
Let’s take a deeper dive into BRCA mutations. We all have
BRCA genes: one copy from mom, and one from dad. If both parents give their
daughter unmutated copies of the BRCA gene, she has that 12% risk of a breast
cancer diagnosis in her life. The cancer risk increase happens with a mutation in
one of the two copies: since only one copy of the mutation increases risk, inheritance
happens in an autosomal dominant fashion.
So, why do some women with BRCA mutations develop breast (or
another related) cancer, while others do not? The development of cancer in the
body based on a predisposition usually manifests in a mechanism called the “two-hit
The first hit is the mutation at birth, and the second hit is later in life
when the cancer begins to form. The interaction of other factors, such as the
environment or other genes in the body, with a preexisting cancer risk mutation
may lead to or prevent cancer development.
Many environmental factors
can cause a second hit. Sun or chemical radiation exposure, alcohol use, poor diet
choices, the process of aging, or tobacco use are some of the most common.
Sometimes, these risk factors don’t even cause mutations, they just change gene
expression. Someone could live the healthiest of lifestyles, but the
interaction of certain genes affects the way that tumors get suppressed. Researchers
at Johns Hopkins also found
that some tissues in the body are just more susceptible to “bad luck” and
random DNA mutations that cause cancer.
The takeaway here is that while genetics can increase our
risk of cancer, only about 5% of all cancers are
due to underlying genetic causes. Of the 1,762,450 estimated cancer diagnoses
this year, about 88,000 will have a direct underlying gene mutation, and almost
one million cases will not. Our environment and random chance play a lot more
into cancer diagnosis than one may expect; being positive for a genetic
mutation that leads to cancer predisposition is NOT a diagnosis, just as being
negative for one of these genes does NOT clear one of a lifetime cancer
diagnosis. The team, and specifically the genetic counselor, at the Sarnoff
Center is open and available to answer any questions or connect you to more
resources related to cancer genetics.