The effect of a single BRCA2 mutation on cancer in Iceland.
Level 3 - non-randomized controlled study
Cohort study using genealogical record linkage and cancer registry data
PubMed 12114473 · doi:10.1136/jmg.39.7.457
What was done
A cohort study in Iceland linked a breast cancer family resource with the Icelandic Cancer Registry to evaluate cancer risk among relatives of breast cancer probands. Out of 995 breast cancer patients, 887 were tested for the specific Icelandic founder mutation BRCA2 999del5 (90 carriers, 797 non-carriers). Relative risks (RR) of malignancies were estimated among first- and second-degree relatives.
What was found
First-degree relatives of probands carrying the BRCA2 999del5 mutation had a relative risk of breast cancer of 7.55 (95% CI 6.04 to 9.03), compared to 1.72 (95% CI 1.49 to 1.96) in first-degree relatives of non-carrier probands. For prostate and ovarian cancer, first- and second-degree relatives of mutation carriers had significantly increased relative risks, whereas no significant familial risk for these cancers was detected in families of non-carriers.
Why it matters
The study quantifies the contribution of a single founder mutation to familial cancer risk at a population scale, demonstrating that BRCA2 999del5 accounts for a major share of familial breast cancer and nearly all familial clustering of prostate and ovarian cancer in Icelandic breast cancer families.
Limits
The findings are specific to the Icelandic population and a single founder mutation (999del5), limiting generalizability to populations with heterogeneous BRCA mutations. The abstract does not provide exact numerical effect estimates or confidence intervals for the prostate and ovarian cancer risks, nor absolute risk figures. Other potential genetic or environmental co-factors in non-carrier familial clustering were not reported.
Cited by
- context Data from Iceland showed that carrying a BRCA2 mutation was associated with a difference of up to seven years in healthy aging/lifespan, predominantly due to cancer.