Abstract
Defective DNA repair may contribute to early age and late stage at time of diagnosis and mutations in critical tumor suppressor genes, such as TP53 in breast cancer. Using DNA samples from 436 breast cancer cases (374 Caucasians and 62 African-Americans), we tested these associations with 18 non-synonymous single-nucleotide polymorphisms (nsSNPs) in four DNA repair pathways: (i) base excision repair: ADPRT V762A, APE1 D148E, XRCC1 R194W/R280H/R399Q and POLD1 R119H; (ii) double-strand break repair: NBS1 E185Q and XRCC3 T241M; (iii) mismatch repair: MLH1 I219V, MSH3 R940Q/T1036A andMSH6 G39E and (iv) nucleotide excision repair: ERCC2 D312N/K751Q, ERCC4 R415Q, ERCC5 D1104H and XPC A499V/K939Q. Younger age at diagnosis (trend <0.001). A similar significant trend was also observed associating TP53 mutations with increasing numbers of risk genotypes for XRCC1 399 QQ, XPC 939 QQ, ERCC4 415 QQ and XPC 499 AA (Ptrend <0.001). Our pilot data suggest that nsSNPs of multiple DNA repair pathways are associated with younger age at diagnosis and TP53 mutations in breast cancer and larger studies are warranted to further evaluate these associations.
| Original language | English |
|---|---|
| Pages (from-to) | 1354-1360 |
| Number of pages | 7 |
| Journal | Carcinogenesis |
| Volume | 32 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2011 |
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ASJC Scopus subject areas
- Cancer Research
Cite this
Genetic polymorphisms of multiple DNA repair pathways impact age at diagnosis and TP53 mutations in breast cancer. / Smith, Tasha R.; Liu-Mares, Wen; van Emburgh, Beth O.; Levine, Edward A.; Allen, Glenn O.; Hill, Jeff W.; Reis, Isildinha M.; Kresty, Laura A.; Pegram, Mark D.; Miller, Mark S.; Hu, Jennifer J.
In: Carcinogenesis, Vol. 32, No. 9, 2011, p. 1354-1360.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Genetic polymorphisms of multiple DNA repair pathways impact age at diagnosis and TP53 mutations in breast cancer
AU - Smith, Tasha R.
AU - Liu-Mares, Wen
AU - van Emburgh, Beth O.
AU - Levine, Edward A.
AU - Allen, Glenn O.
AU - Hill, Jeff W.
AU - Reis, Isildinha M.
AU - Kresty, Laura A.
AU - Pegram, Mark D.
AU - Miller, Mark S.
AU - Hu, Jennifer J.
PY - 2011
Y1 - 2011
N2 - Defective DNA repair may contribute to early age and late stage at time of diagnosis and mutations in critical tumor suppressor genes, such as TP53 in breast cancer. Using DNA samples from 436 breast cancer cases (374 Caucasians and 62 African-Americans), we tested these associations with 18 non-synonymous single-nucleotide polymorphisms (nsSNPs) in four DNA repair pathways: (i) base excision repair: ADPRT V762A, APE1 D148E, XRCC1 R194W/R280H/R399Q and POLD1 R119H; (ii) double-strand break repair: NBS1 E185Q and XRCC3 T241M; (iii) mismatch repair: MLH1 I219V, MSH3 R940Q/T1036A andMSH6 G39E and (iv) nucleotide excision repair: ERCC2 D312N/K751Q, ERCC4 R415Q, ERCC5 D1104H and XPC A499V/K939Q. Younger age at diagnosis (trend <0.001). A similar significant trend was also observed associating TP53 mutations with increasing numbers of risk genotypes for XRCC1 399 QQ, XPC 939 QQ, ERCC4 415 QQ and XPC 499 AA (Ptrend <0.001). Our pilot data suggest that nsSNPs of multiple DNA repair pathways are associated with younger age at diagnosis and TP53 mutations in breast cancer and larger studies are warranted to further evaluate these associations.
AB - Defective DNA repair may contribute to early age and late stage at time of diagnosis and mutations in critical tumor suppressor genes, such as TP53 in breast cancer. Using DNA samples from 436 breast cancer cases (374 Caucasians and 62 African-Americans), we tested these associations with 18 non-synonymous single-nucleotide polymorphisms (nsSNPs) in four DNA repair pathways: (i) base excision repair: ADPRT V762A, APE1 D148E, XRCC1 R194W/R280H/R399Q and POLD1 R119H; (ii) double-strand break repair: NBS1 E185Q and XRCC3 T241M; (iii) mismatch repair: MLH1 I219V, MSH3 R940Q/T1036A andMSH6 G39E and (iv) nucleotide excision repair: ERCC2 D312N/K751Q, ERCC4 R415Q, ERCC5 D1104H and XPC A499V/K939Q. Younger age at diagnosis (trend <0.001). A similar significant trend was also observed associating TP53 mutations with increasing numbers of risk genotypes for XRCC1 399 QQ, XPC 939 QQ, ERCC4 415 QQ and XPC 499 AA (Ptrend <0.001). Our pilot data suggest that nsSNPs of multiple DNA repair pathways are associated with younger age at diagnosis and TP53 mutations in breast cancer and larger studies are warranted to further evaluate these associations.
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UR - http://www.scopus.com/inward/citedby.url?scp=80052413954&partnerID=8YFLogxK
U2 - 10.1093/carcin/bgr117
DO - 10.1093/carcin/bgr117
M3 - Article
C2 - 21700777
AN - SCOPUS:80052413954
VL - 32
SP - 1354
EP - 1360
JO - Carcinogenesis
JF - Carcinogenesis
SN - 0143-3334
IS - 9
ER -