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Haplotype analysis of eight genes of the monoubiquitinated FANCD2-DNA damage-repair pathway in breast cancer patients.

Abstract：

BACKGROUND:Ten genes are associated with increased susceptibility to inherited breast cancer have also been associated with population breast cancer risk, and all are involved directly or indirectly in the monoubiquitinated FANCD2-DNA damage repair pathway. We analyzed 13 haplotype blocks in eight of these genes to estimate the breast cancer risk conferred by individual haplotypes. METHODS:Haplotype blocks were constructed with 48 tag single-nucleotide polymorphisms (tSNPs) identified in eight breast cancer susceptibility genes, TP53, PTEN, CHEK2, ATM, NBS1, RAD50, BRIP1, and PALB2. Genotyping was performed by SNPscan on 734 female patients and 672 female age-matched controls. RESULTS:Forty-five tSNPs were successfully genotyped by SNPscan, and call rates for each tSNP were above 98.9%. Thirteen haplotype blocks of eight genes were constructed with 41 successfully genotyped tSNPs. We found that seven haplotypes from four haplotype blocks located within three genes (NBS1, PTEN, and BRIP1) were significantly associated with breast cancer risk. Among these, four haplotypes (ATC in block 1 of NBS1, GCCCC and GCCCT in block 2 of NBS1, and GCT in block 2 of BRIP1) were correlated with breast cancer risk in sporadic cases (OR (95% CI) 1.350(1.124-1.623), 0.752(0.584-0.969), 0.803(0.649-0.993), and 0.776(0.604-0.997), respectively), and only one haplotype (GGCCT in block 2 of NBS1) was significantly associated with breast cancer risk in familial and early-onset cases (OR(95% CI) 1.902(1.134-3.191)). CONCLUSIONS:Four haplotypes within two genes (NBS1 and BRIP1) involved in the monoubiquitinated FANCD2-DNA damage-repair pathway are significantly associated with increased sporadic breast cancer risk, while one haplotype within NBS1 is correlated with an increased risk of familial or early-onset breast cancer, indicating that specific haplotypes may be distinct predictors of breast cancer.

journal_name

Cancer Epidemiol

journal_title

Cancer epidemiology

authors

Tang LL,Chen FY,Wang H,Hu XL,Dai X,Mao J,Shen ZT,Wu YH,Wang SM,Hai J,Yan GJ,Li H,Huang J

doi

10.1016/j.canep.2012.12.010

subject

Has Abstract

pub_date

2013-06-01 00:00:00

pages

311-7

issue

eissn

1877-7821

issn

1877-783X

pii

S1877-7821(13)00003-9

journal_volume

pub_type

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Haplotype analysis of eight genes of the monoubiquitinated FANCD2-DNA damage-repair pathway in breast cancer patients.