Polymorphisms in BRCA1, BRCA1-interacting genes and susceptibility of breast cancer in Chinese women.
OBJECTIVE
BRCA1-interacting protein C-terminal helicase 1 (BRIP1) and zinc finger protein 350 (ZNF350) work with BRCA1 in tumor suppression procedures. Low penetrance variants of these three genes may jointly affect individuals' breast cancer susceptibility in general population.


METHODS
We focused on potentially functional single nucleotide polymorphisms (SNPs) in the coding regions of BRIP1, ZNF350 and BRCA1 and pairwise-tagging approach was used to minimize the number of SNPs. Five SNPs were selected and genotyped by PCR-restriction fraction length polymorphism or PCR-primer introduced restriction analysis assays in a case-control study with 568 breast cancer cases and 624 controls in a Chinese population.


RESULTS
All of the five SNPs except rs2278415 of ZNF350 conferred a modestly increased risk, although, with no statistical significance. Joint effect analyses indicated that all the variant genotypes of ZNF350 polymorphisms accounted for increased breast cancer risk among subjects carrying variant homozygote of BRCA1 rs799917, particularly for ZNF350 rs4986773 (OR = 2.03, 95%CI = 1.02-4.05, the test for gene-gene interaction P (int) = 0.059).


CONCLUSIONS
BRCA1 and ZNF350 may jointly contribute to individuals' susceptibility of breast cancer in Chinese women. Further functional studies are warranted to validate our findings.
Huo
Xiang
X
Laboratory of Reproductive Medicine, Cancer Center of Nanjing Medical University, Nanjing 210029, China.
Lu
Cheng
C
Huang
Xinen
X
Hu
Zhibin
Z
Jin
Guangfu
G
Ma
Hongxia
H
Wang
Xuechen
X
Qin
Jianwei
J
Wang
Xinru
X
Shen
Hongbing
H
Tang
Jinhai
J
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D051856:Fanconi Anemia Complementation Group Proteins; D005260:Female; D019398:Genes, BRCA1; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D020365:RNA Helicases / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*
D004268:DNA-Binding Proteins; D051856:Fanconi Anemia Complementation Group Proteins; D012097:Repressor Proteins; C422407:ZNF350 protein, human; C000618935:BRIP1 protein, human; D020365:RNA Helicases