Anybody BRCA2 positive?

[MizLeelee]

Hi everyone,I was diagnosed with high count MBL (pre-CLL) last Spring, and have recently found out that my father and all his living siblings (all elderly now) are BRCA2 positive.

BRCA2 is one of the two genetic mutations that leads to a significantly increased risk of breast and prostate cancer (and maybe also to some degree stomach and pancreatic cancer).

Does anyone here have any information about a connection between BRCA2 and CLL? I'm asking because as you might imagine all my cousins are now having to get genetic testing and I'm trying to decide whether I need to disclose my MBL diagnosis to them. I'm not eager to have my children find out about it too soon, and also, my only relative with CLL is on the other (non BRCA) side of the family.

Thank you!!

[lindalou5]

along with removal of both breasts due to invasive ductal and lobular cancer, I will be genetically and environmental tested. CLL and breast cancer run in my family for at least three generations. My paternal grandmother had both as do I. So for about $700.00-being paid for by someone else-I will find out some decent info. I can let you know what that will be if you want. I think the geneticist said they run about 200 + tests. I am doing the tests for my granddaughter and the rest of the younger ones in family who may decide not to procreate because of their genetics. At least they will find out the chances of these diseases becoming part of their lives.

[MizLeelee in reply to lindalou5]

Wow, lindalou5, that's a lot to deal with. I'm sure your relatives will be grateful for the information. Best wishes to you.

[dkay]

There is an association. See sciencedirect.com/journal/b.... This is an article by Rudd et al. In the journal Blood from 2006. Also, an article by Iqbal from the British Journal of Cancer in 2016. ncbi.nlm.nih.gov/pmc/articl....

The increased relative risk is lower than for associated breast cancer but it is increased.

[bennevisplace in reply to dkay]

Thanks, but... the first link is incomplete - it only takes me to Blood Journal's About page. I have issues with the second reference: all but one of the leukemia cases in mutated BRCA carriers were acute myeloid leukemia, diagnosed following, thus potentially triggered by, chemotherapy for breast cancer. A single case of CLL with BRCA2 hardly establishes an association.

[bennevisplace]

I did a quick trawl on google and didn't find convincing evidence of a link between CLL and BRCA status.

There are some old studies pointing out that normal BRCA1 and 2 genes are vital in DNA repair, so theoreticaly a deleterious mutation could increase the chance of any kind of cancer, and one or two papers have focused on haematological cancers / CLL e.g. ashpublications.org/blood/a... but note, this paper lumps BRCA2 together with the well-known damage response pathway orchestrated by ATM.

A bit more recent, this study acsjournals.onlinelibrary.w... counted different cancers associated with BRCA1 and 2 mutations in hospital patients. The results: Among the 1072 mutation carriers, 1177 cancers of 30 different cancer types were identified. Individuals with a BRCA1 mutation did not have a significant increase in cancers other than breast and ovarian cancer; however, a trend in melanoma was observed. Individuals with a BRCA2 mutation had significantly higher numbers of observed cases versus expected cases for pancreatic cancer in both men and women (SIR, 21.7; 95% confidence interval [CI], 13.1-34.0; P < .001) and for prostate cancer in men (SIR, 4.9; 95% CI, 2.0-10.1; P = .002).

In detail, there was a single case of NHL, of which CLL is one variety, and 8 cases of leukemia, of which there are many varieties both lymphoid, acute and chronic (CLL again), and myeloid. It's very likely that the 8 cases recorded as leukemia include AMLs following chemotherapy for prior cancer.

[MizLeelee in reply to bennevisplace]

Good to know, bennevisplace!!