stuff or nonsense?
BACKGROUND:
Despite
classification of the
BRCA2c.9976A>T, p.(Lys3326Ter) variant as a
polymorphism, it has been associated with increased risks of pancreatic,
lung, oesophageal and breast cancer.
METHODS:
We
have noticed multiple
co-occurrences of the BRCA2 c.9976A>T variant
with the pathogenic BRCA2c.6275_6276delTT frameshift mutation
p.(Leu2092ProfsTer7) and using a cohort study have assessed if this
might account for these tumour risk associations.
RESULTS:
We
identified 52 families with BRCA2c.6275_6276delTT, all of which occur
in cis with the BRCA2c.9976A>T variant allele as demonstrated by
co-segregation in all family members tested.
Of 3245 breast/ovarian
cancer samples sequenced for BRCA2, only 43/3245 (1.3%) carried BRCA2
c.9976A>T alone, after excluding individuals with
BRCA2c.6275_6276delTT (n=22) or other BRCA1 (n=3) or BRCA2 (n=2)
pathogenic mutations. The resultant frequency (1.3%) after removal of
co-occurring mutations is lower than the 1.7% and 1.67% frequencies from
two control populations for BRCA2 c.9976A>T, but similar to the
1.39% seen in the
Exome Aggregation Consortium database. We did not
identify increased frequencies of oesophageal, pancreatic or lung cancer
in families with just BRCA2 c.9976A>T using person-years at risk
analysis.
CONCLUSIONS:
It
is likely that the previous associations of increased cancer risks due
to BRCA2c.9976A>T represent
reporting bias and are contributed to
because the variant is in LD with BRCA2c.6275_6276delTT.
choices?
"Overwhelmingly Canadian patients have voiced their support for assisted-dying and yet 'we' are still not listening but using many excuses why not. It is about choice - the patients' choice as they are truly and ultimately the ones affected by the decision, that which is being made by others. Many high profile physicians (and other healthcare providers) - prior to dying - have made their opinions on the role of assisted-dying clear. We all know the names - Dr Donald Low is one. It is to understand that medicine today, as we know it, is unable, in selected cases, to resolve extreme pain and agony and yet - we wish to prolong this suffering at any cost? As a cancer survivor (3 times so far) I have personally witnessed (non- medical background) cancer friends begging to die. Begging. They have begged their 'god' to die. For anyone who has witnessed these intimate experiences - they leave terrible emotional scars. Ultimately the question remains as to why we would continue to witness these events knowing that no medical intervention is available to ease these sufferings. This is where the choice - the patients' choice - demands compassion, integrity and 'to do no further harm'."