Dataset Information

A functionally significant SNP in TP53 and breast cancer risk in African-American women.

ABSTRACT: A coding region polymorphism exists in the TP53 gene (Pro47Ser; rs1800371) in individuals of African descent, which reduces p53 tumor suppressor function in a mouse model. It has been unclear whether this functionally significant polymorphism alters cancer risk in humans. This analysis included 6907 women with breast cancer and 7644 controls from the AMBER, ROOT, and AABC consortia. We used multivariable logistic regression to estimate associations between the TP53 Pro47Ser allele and overall breast cancer risk. Because polymorphisms in TP53 tend to be associated with cancer risk in pre-menopausal women, we also limited our analyses to this population in the AMBER and ROOT consortia, where menopausal status was known, and conducted a fixed effects meta-analysis. In an analysis of all women in the AMBER, ROOT, and AABC consortia, we found no evidence for association of the Pro47Ser variant with breast cancer risk. However, when we restricted our analysis to only pre-menopausal women from the AMBER and ROOT consortia, there was a per allele odds ratio of 1.72 (95% confidence interval 1.08-2.76; p-value?=?0.023). Although the Pro47Ser variant was not associated with overall breast cancer risk, it may increase risk among pre-menopausal women of African ancestry. Following up on more studies in human populations may better elucidate the role of this variant in breast cancer etiology. However, because of the low frequency of the polymorphism in women of African ancestry, its impact at a population level may be minimal.

SUBMITTER: Murphy ME

PROVIDER: S-EPMC5445618 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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A functionally significant SNP in TP53 and breast cancer risk in African-American women.

Murphy Maureen E ME Liu Song S Yao Song S Huo Dezheng D Liu Qin Q Dolfi Sonia C SC Hirshfield Kim M KM Hong Chi-Chen CC Hu Qiang Q Olshan Andrew F AF Ogundiran Temidayo O TO Adebamowo Clement C Domchek Susan M SM Nathanson Katherine L KL Nemesure Barbara B Ambs Stefan S Blot William J WJ Feng Ye Y John Esther M EM Bernstein Leslie L Zheng Wei W Hu Jennifer J JJ Ziegler Regina G RG Nyante Sarah S Ingles Sue A SA Press Michael F MF Deming Sandra L SL Rodriguez-Gil Jorge L JL Haiman Christopher A CA Olopade Olufunmilayo I OI Lunetta Kathryn L KL Palmer Julie R JR Ambrosone Christine B CB

NPJ breast cancer 20170227

A coding region polymorphism exists in the <i>TP53</i> gene (Pro47Ser; rs1800371) in individuals of African descent, which reduces p53 tumor suppressor function in a mouse model. It has been unclear whether this functionally significant polymorphism alters cancer risk in humans. This analysis included 6907 women with breast cancer and 7644 controls from the AMBER, ROOT, and AABC consortia. We used multivariable logistic regression to estimate associations between the TP53 Pro47Ser allele and ove ...[more]

PMID: 28649645

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Project description:Breast cancer risk prediction remains imperfect, particularly among non-white populations. This study examines the impact of including single-nucleotide polymorphism (SNP) alleles in risk prediction for white and African American women undergoing screening mammogram. Using a prospective cohort study, standard risk information and buccal swabs were collected at the time of screening mammography. A 12 SNP panel was performed by deCODE genetics. Five-year and lifetime risks incorporating SNPs were calculated by multiplying estimated Breast Cancer Risk Assessment Tool (BCRAT) risk by the total genetic risk ratio. Concordance between the BCRAT and the combined model (BCRAT + SNPs) in identifying high-risk women was measured using the kappa statistic. SNP data were available for 810 women (39 % African American, 55 % white). The mean BCRAT 5-year risk was 1.71 % for whites and 1.18 % for African Americans. Mean genetic risk ratios were 1.09 in whites and 1.29 in African Americans. Among whites, three SNPs had higher frequencies, and among African Americans, seven SNPs had higher and four had lower high-risk allele frequencies than previously reported. Agreement between the BCRAT and the combined model was relatively low for identifying high-risk women (5-year ? = 0.54, lifetime ? = 0.36). Addition of SNPs had the greatest effect among African Americans, with 12.4 % identified as having high-5-year risk by BCRAT, but 33 % by the combined model. A greater proportion of African Americans were reclassified as having high-5-year risk than whites using the combined model (21 vs. 10 %). The addition of SNPs to the BCRAT reclassifies the high-risk status of some women undergoing screening mammography, particularly African Americans. Further research is needed to determine the clinical validity and utility of the SNP panel for use in breast cancer risk prediction, particularly among African Americans for whom these risk alleles have generally not been validated.

Dataset Information

A functionally significant SNP in TP53 and breast cancer risk in African-American women.

Publications

A functionally significant SNP in TP53 and breast cancer risk in African-American women.

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