Association of BRCA2 K3326* With Small Cell Lung Cancer and Squamous Cell Cancer of the Skin.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Sigurjonsdottir, Gudbjorg R
Stacey, Simon N
Pardo, Luba M
Sigurdsson, Stefan T
Olafsdottir, Gudridur H
Jonasson, Jon G
Sigurdsson, Jon K
Vermeulen, Sita H
Galesloot, Tessel E
Allain, Dawn C
Johannsson, Oskar T
Ragnarsson, Gunnar B
Gudbjartsson, Daniel F
Kiemeney, Lambertus A M L
Ewart Toland, Amanda
Peters, Wilbert H M
Olafsson, Jon H
MetadataShow full item record
CitationAssociation of BRCA2 K3326* With Small Cell Lung Cancer and Squamous Cell Cancer of the Skin. 2018, 110(9):967-974 Journal of the National Cancer Institute
AbstractMost pathogenic mutations in the BRCA2 gene carry a high risk of hereditary breast and ovarian cancer (HBOC). However, a stop-gain mutation, K3326* (rs11571833), confers risk of lung cancer and cancers of the upper-aero-digestive tract but only a modest risk of breast or ovarian cancer. The Icelandic population provides an opportunity for comprehensive characterization of the cancer risk profiles of K3326* and HBOC mutations because a single mutation, BRCA2 999del5, is responsible for almost all BRCA2-related HBOC in the population. Genotype information on 43 641 cancer patients and 370 971 control subjects from Iceland, the Netherlands, and the United States was used to assess the cancer risk profiles of K3326* and BRCA2 999del5. BRCA2 expression was assessed using RNAseq data from blood (n = 2233), as well as 52 tissues reported in the GTEx database. The cancer risks associated with K3326* are fundamentally different from those associated with 999del5. We report for the first time an association between K3326* and small cell lung cancer (odds ratio [OR] = 2.06, 95% confidence interval [CI] = 1.35 to 3.16) and squamous cell carcinoma of the skin (OR = 1.69, 95% CI = 1.26 to 2.26). Individuals homozygous for K3326* reach old age and have children. Unlike BRCA2 999del5, the K3326* allele does not affect the level of BRCA2 transcripts, and the allele is expressed to the same extent as the wild-type allele. K3326* associates primarily with cancers that have strong environmental genotoxic risk factors. Expression of the K3326* allele suggests that a variant protein may be made that retains the DNA repair capabilities important to hormone-responsive tissues but may be less efficient in responding to genotoxic stress.
DescriptionTo access publisher's full text version of this article click on the hyperlink below
- The BARD1 Cys557Ser variant and breast cancer risk in Iceland.
- Authors: Stacey SN, Sulem P, Johannsson OT, Helgason A, Gudmundsson J, Kostic JP, Kristjansson K, Jonsdottir T, Sigurdsson H, Hrafnkelsson J, Johannsson J, Sveinsson T, Myrdal G, Grimsson HN, Bergthorsson JT, Amundadottir LT, Gulcher JR, Thorsteinsdottir U, Kong A, Stefansson K
- Issue date: 2006 Jul
- The Icelandic founder mutation BRCA2 999del5: analysis of expression.
- Authors: Mikaelsdottir EK, Valgeirsdottir S, Eyfjord JE, Rafnar T
- Issue date: 2004
- Population-based study of changing breast cancer risk in Icelandic BRCA2 mutation carriers, 1920-2000.
- Authors: Tryggvadottir L, Sigvaldason H, Olafsdottir GH, Jonasson JG, Jonsson T, Tulinius H, Eyfjörd JE
- Issue date: 2006 Jan 18
- Establishment of three human breast epithelial cell lines derived from carriers of the 999del5 BRCA2 Icelandic founder mutation.
- Authors: Rubner Fridriksdottir AJ, Gudjonsson T, Halldorsson T, Björnsson J, Steinarsdottir M, Johannsson OT, Ogmundsdottir HM
- Issue date: 2005 Nov-Dec
- Intra-abdominal carcinomatosis after prophylactic oophorectomy in women of hereditary breast ovarian cancer syndrome kindreds associated with BRCA1 and BRCA2 mutations.
- Authors: Casey MJ, Synder C, Bewtra C, Narod SA, Watson P, Lynch HT
- Issue date: 2005 May