Blogger's Note: the
other cancers (KRAS mutations) referred to beyond ovarian and breast cancers include references to lung and melanoma cancers; KRAS mutations have been established in colorectal cancers, however, there are no references on this particular subject within this research article regarding Lynch Syndrome -
an ongoing area of specific
research (re: KRAS/Lynch Syndrome/blog posting of May 16, 2012 Jnl ASCP)
~~~~~~~~~~~~~~~~~~~
PLoS ONE: The KRAS-Variant Is Associated with Risk of Developing Double Primary Breast and Ovarian Cancer
Table 1. The KRAS-variant is significantly associated with uninformative breast and ovarian cancer patients.
doi:10.1371/journal.pone.0037891.t001
Purpose
A germline microRNA binding site-disrupting variant, the
KRAS-variant (rs61764370),
is associated with an increased risk of developing several cancers.
Because this variant is most strongly associated with ovarian cancer
risk in patients from hereditary breast and ovarian families (HBOC), and
with the risk of premenopausal triple negative breast cancer,
we
evaluated the association of the KRAS-variant with women with personal histories of both breast and ovarian cancer, referred to as double primary patients.
Conclusions
These findings further validate the importance of the
KRAS-variant
in breast and ovarian cancer risk, and
support the association of this
variant as a genetic marker for HBOC families previously considered
uninformative.
Introduction
Hereditary
breast and ovarian cancer (HBOC) syndrome is an inherited
cancer-susceptibility syndrome marked by an increased risk of developing
both ovarian cancer and breast cancer
[1].
Families generally considered as having HBOC syndrome are those with
multiple family members that have one of these cancers, especially at
young ages, or an individual with a cancer in both organs, a “double
primary” patient. While this is a relatively rare presentation, a
substantial number of women develop both breast and ovarian primaries
over their lifetime. While
BRCA1 and
BRCA2 are strongly associated with HBOC syndrome
[2],
a large number of HBOC families and women with double primary cancer do
not have detectable genetic mutations (herein referred to as
“uninformative” patients).
The chances of
identifying a mutation causative for HBOC increase when testing
individuals diagnosed with double breast/ovarian primaries
[3]–
[5]. However, a recent report suggests that the rates of
BRCA
mutations are not higher in a patient with a double primary without a
family history than that for isolated first degree relative pairs with
single primaries (14% versus 17% with mutations, respectively)
[4]. This supports the importance of family history even in patients with double primary cancers. Although
BRCA
mutations were found in 49% of double primary patients in this recent
analysis, it should be noted that this indicates that over half of
double primary patients do not have a known genetic cause for their
disease. This is consistent with other reports of these patients
[3],
[5].............
The goal of this study was to determine the association of the
KRAS-variant
with women with double primary breast and ovarian cancer, to further
validate the association of this variant with HBOC families. Findings
here support the importance of the
KRAS-variant in uninformative HBOC families as well as in predicting the risk of
multiple primary cancers in women.......
Association of the KRAS-variant with Multiple Cancers in All Patients
Because the KRAS-variant has been found to be associated with an increased risk for other cancers besides breast and ovarian cancer [11],
[15] we tested the hypothesis that the
KRAS-variant would predict for an increased risk of developing additional cancers in this double primary cohort, regardless of
BRCA mutation status. For 183 of the patients in our study where this information was available, 79.2% (
n = 145) had reported just the two cancers (breast and ovarian), 12.0% (
n = 22) had two separate primary breast cancers and also ovarian cancer, and
8.7% (n = 16) had cancer in an additional organ outside of the breast and ovary (triple primary).