Polymorphisms in the TOX3/LOC643714 locus and risk of breast cancer in African-American women.
BACKGROUND
The rs3803662 single nucleotide polymorphism (SNP) in the TOX3/LOC643714 region was identified as a breast cancer susceptibility genetic variant in recent genome-wide association studies of women of European ancestry and has been replicated in other populations of European ancestry. The position of the causal variant tagged by the rs3803662 marker is still unknown. In fact, because the rs3803662 polymorphism is located between the TOX3 and the LOC643714 loci, it is unclear which gene is the one causally related to the risk of breast cancer. Because linkage disequilibrium blocks are smaller in populations of African ancestry, fine-mapping in African ancestry samples might be an effective approach to narrowing the position of the causal variant(s) in the TOX3/LOC643714 locus.


METHODS
We evaluated a total of 60 tagging SNPs throughout the TOX3/LOC643714 region in a nested case-control study of breast cancer within the Black Women's Health Study, which included 906 cases and 1,111 controls.


RESULTS
No significant association was found for the rs3803662 SNP. However, four other SNPs (rs3104746, rs3112562, rs3104793, and rs8046994), all of them located in the LOC643714 gene, were associated with risk of breast cancer. The strongest association was observed for rs3104746: each copy of the A-rs3104746 allele was associated with a 23% higher risk of breast cancer (odds ratios, 1.23; 95% confidence intervals, 1.05-1.44; P=0.009).


CONCLUSIONS
Our results confirm the association observed in genome-wide association studies of European ancestry populations.


CONCLUSIONS
The results narrow the locus to a smaller linkage disequilibrium block in the LOC643714 gene.
Ruiz-Narváez
Edward A
EA
Slone Epidemiology Center at Boston University, Department of Epidemiology, School of Public Health, 1010 Commonwealth Avenue, Boston MA 02215, USA. eruiznar@bu.edu
Rosenberg
Lynn
L
Cozier
Yvette C
YC
Cupples
L Adrienne
LA
Adams-Campbell
Lucile L
LL
Palmer
Julie R
JR
D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D051017:Apoptosis Regulatory Proteins; D001943:Breast Neoplasms / Q000208:ethnology* / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D055106:Genome-Wide Association Study; D006609:High Mobility Group Proteins; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011980:Receptors, Progesterone / Q000235:genetics*; D012307:Risk Factors; D015996:Survival Rate; D015534:Trans-Activators; D055815:Young Adult
D051017:Apoptosis Regulatory Proteins; D006609:High Mobility Group Proteins; D011980:Receptors, Progesterone; C521752:TOX3 protein, human; D015534:Trans-Activators
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