Evaluation of breast cancer susceptibility loci in Chinese women.
BACKGROUND
Recent genome-wide association studies (GWAS), mostly conducted among women of European ancestry, have identified 16 single-nucleotide polymorphisms (SNP) associated with breast cancer.


METHODS
We evaluated these SNPs with the risk of breast cancer and further by estrogen receptor status in a population-based study of 6,498 cases and 3,999 controls in Chinese women. We also searched for novel genetic risk variants in four loci, 2q35, 5p12/MRPS30, 8q24.21, and 17q23.2/COX11, in a two-stage study. In stage I, 868 SNPs were analyzed in 2,073 cases and 2,084 controls. In stage II, 58 SNPs selected from stage I were evaluated, including 4,425 cases and 1,915 controls.


RESULTS
Statistically significant associations (P < 0.05) were observed for eight GWAS-identified SNPs, including rs4973768 (3p24/SLC4A7), rs889312 (5q11.2MAP3K1), rs2046210 (6q25.1), rs1219648 (10q26.13/FGFR2), rs2981582 (10q26.13/FGFR2), rs3817198 (11p15.5/LSP1), rs8051542 (16q12.1/TOX3), and rs3803662 (16q12.1/TOX3). Two additional SNPs, rs10941679 (5p12/MRPS30) and rs13281615 (8q24.21), showed a marginally significant association. Some of these associations varied by estrogen receptor status. In the fine-mapping analysis, five SNPs showed a consistent association with breast cancer risk in both stages: rs10169372 (2q35), rs283720 (8q24.21), rs10515083 (17q23.2/COX11), rs16955329 (17q23.2/COX11), and rs2787487 (17q23.2/COX11).


CONCLUSIONS
This study shows that approximately half of the SNPs initially reported from GWAS of breast cancer in European descendants can be directly replicated in Chinese. Our fine-mapping analyses revealed several candidates of risk variants that can be further evaluated in studies with a larger sample size.


CONCLUSIONS
Findings from this study may help guide future fine-mapping studies to identify causal variants for breast cancer.
Long
Jirong
J
Division of Epidemiology, Department ofMedicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Nashville, TN 37203-1738, USA. Jirong.Long@vanderbilt.edu
Shu
Xiao-Ou
XO
Cai
Qiuyin
Q
Gao
Yu-Tang
YT
Zheng
Ying
Y
Li
Guoliang
G
Li
Chun
C
Gu
Kai
K
Wen
Wanqing
W
Xiang
Yong-Bing
YB
Lu
Wei
W
Zheng
Wei
W
D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011960:Receptors, Estrogen / Q000096:biosynthesis; D012307:Risk Factors
D011960:Receptors, Estrogen