PHILADELPHIA — Among patients
with breast cancer, lung cancer, or chronic lymphocytic leukemia (CLL), those
who had a specific form of the CYP3A7 gene (CYP3A7*1C) had worse outcomes
compared with those who did not have CYP3A7*1C, and this may be related to how
the patients metabolize, or break down, the therapeutics used to treat them,
according to a study published in Cancer
journal of the American
Association for Cancer Research.
“The CYP3A7 gene encodes an
enzyme that breaks down all sorts of naturally occurring substances—such as sex
steroids like estrogen and testosterone—as well as a wide range of drugs that
are used in the treatment of cancer,” said Olivia
Fletcher, PhD, a
senior investigator at the Breast Cancer Now Toby Robins Research Centre at
of Cancer Research in London. “The CYP3A7 gene is
normally turned on in an embryo and then turned off shortly after a baby is
born, but individuals who have one or more copy of the CYP3A7*1C form of the
gene [the CYP3A7*1C allele] turn on their CYP3A7 gene in adult life.
“We found that individuals with
breast cancer, lung cancer, or CLL who carry one or more copy of the CYP3A7*1C
allele tend to have worse outcomes,” continued Fletcher. “One possibility is
that these patients break down the drugs that they are given to treat their
cancer too fast. However, further independent studies that replicate our
findings in larger numbers of patients and rule out biases are needed before we
could recommend any changes to the treatment that cancer patients with the
CYP3A7*1C allele receive.”
To find out whether the CYP3A7*1C
allele was associated with outcome for patients with breast cancer, lung cancer,
or CLL, Fletcher and colleagues analyzed DNA samples from 1,008 breast cancer
patients, 1,142 patients with lung cancer, and 356 patients with CLL for the
presence of a single nucleotide polymorphism (SNP), rs45446698. Fletcher
explained that a SNP is a type of genetic variant and that because of the way
that we inherit our genetic material from our parents, we tend to inherit
clusters of genetic variants. She went on to say that rs45446698 is one of seven
SNPs that cluster together, forming the CYP3A7*1C allele.
The researchers found that among
the breast cancer patients, rs45446698 (and, therefore, the CYP3A7*1C allele)
was associated with a 74 percent increased risk of breast cancer mortality.
Among the lung cancer patients, it was associated with a 43 percent increased
risk of death from any cause, and among the CLL patients, it was associated with
a 62 percent increased risk of disease progression.
Patients who were treated with a
chemotherapeutic broken down by CYP3A7 tended to have worse outcomes compared
with those treated with other chemotherapeutics, but the difference was not
“Even though we did not see a
statistically significant difference when stratifying patients by treatment with
a CYP3A7 substrate, the fact that we see the same effect in three very different
cancer types suggests to me that it is more likely to be something to do with
treatment than the disease itself,” said Fletcher. “However, we are looking at
ways of replicating these results in additional cohorts of patients and types of
cancer, as well as overcoming the limitations of this study.”
Fletcher explained that the main
limitation of the study is that the researchers used samples and clinical
information collected for other studies. Therefore, they did not have the same
clinical information for each patient, and the samples were collected at
different time points and for patients treated with various chemotherapeutics.
She also noted that the team were not able to determine how quickly the patients
broke down the therapeutics they received as treatment.
The study was supported by Breast
Cancer Now, Leukaemia and Lymphoma Research (now known as Bloodwise), Cancer
Research UK, the Medical Research Council, the Cridlan Trust, the Helen Rollason
Cancer Charity, and Sanofi-Aventis. Funding for the authors’ institutions was
received from the National Health Service of the United Kingdom. Fletcher
declares no conflicts of interest.