High prevalence of BRCA1 and BRCA2 mutations in unselected Nigerian breast cancer patients.
Inherited mutations in the BRCA1 and BRCA2 genes are the strongest genetic predictors of breast cancer and are the primary causes of familial breast/ovarian cancer syndrome. The frequency, spectrum and penetrance of mutant BRCA1/BRCA2 alleles have been determined for several populations, but little information is available for populations of African ancestry, who suffer a disproportionate burden of early onset breast cancer. We have performed complete sequence analysis of all BRCA1 and BRCA2 exons and intron-exon boundaries for 434 Nigerian breast cancer patients from the University College Hospital in Ibadan, Nigeria. In contrast to previous suggestions that BRCA1/BRCA2 mutation frequencies are low or undetectable in African American populations, we find that Nigerian breast cancer patients have an exceptionally high frequency of BRCA1 and BRCA2 mutations (7.1 and 3.9%, respectively). Sixteen different BRCA1 mutations were detected, seven of which have never been reported previously, while thirteen different BRCA2 mutations were seen, six of which were previously unreported. Thus, our data support enrichment for genetic risk factors in this relatively young cohort. To improve breast cancer outcomes, we suggest that family-based models of risk assessment and genetic counseling coupled with interventions to reduce breast cancer risk should be broadly disseminated in Nigeria and other underserved and understudied populations.
Department of Medicine, University of Chicago, Chicago, IL 60637, USA. jfackent@medicine.bsd.uchicago.edu
James D
JD
Fackenthal
Jing
J
Zhang
Bifeng
B
Zhang
Yonglan
Y
Zheng
Fitsum
F
Hagos
Devin R
DR
Burrill
Qun
Q
Niu
Dezheng
D
Huo
Walmy E
WE
Sveen
Temidayo
T
Ogundiran
Clemet
C
Adebamowo
Abayomi
A
Odetunde
Adeyinka G
AG
Falusi
Olufunmilayo I
OI
Olopade
D001741:Black or African American / Q000235:genetics; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D015331:Cohort Studies; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D059645:Mutation Rate; D009549:Nigeria / Q000453:epidemiology; D015995:Prevalence; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate
D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D004273:DNA, Neoplasm