Genetic variants in microRNA and microRNA biogenesis pathway genes and breast cancer risk among women of African ancestry

Frank Qian, Ye Feng, Yonglan Zheng, Temidayo O. Ogundiran, Oladosu Ojengbede, Wei Zheng, William Blot, Christine B. Ambrosone, Esther M. John, Leslie Bernstein, Jennifer Hu, Regina G. Ziegler, Sarah Nyante, Elisa V. Bandera, Sue A. Ingles, Michael F. Press, Katherine L. Nathanson, Anselm Hennis, Barbara Nemesure, Stefan Ambs & 4 others Laurence N. Kolonel, Olufunmilayo I. Olopade, Christopher A. Haiman, Dezheng Huo

Research output: Contribution to journalArticle

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Abstract

MicroRNAs (miRNA) regulate breast biology by binding to specific RNA sequences, leading to RNA degradation and inhibition of translation of their target genes. While germline genetic variations may disrupt some of these interactions between miRNAs and their targets, studies assessing the relationship between genetic variations in the miRNA network and breast cancer risk are still limited, particularly among women of African ancestry. We systematically put together a list of 822 and 10,468 genetic variants among primary miRNA sequences and 38 genes in the miRNA biogenesis pathway, respectively; and examined their association with breast cancer risk in the ROOT consortium which includes women of African ancestry. Findings were replicated in an independent consortium. Logistic regression was used to estimate the odds ratio (OR) and 95 % confidence intervals (CI). For overall breast cancer risk, three single-nucleotide polymorphisms (SNPs) in miRNA biogenesis genes DROSHA rs78393591 (OR = 0.69, 95 % CI: 0.55–0.88, P = 0.003), ESR1 rs523736 (OR = 0.88, 95 % CI: 0.82–0.95, P = 3.99 × 10−4), and ZCCHC11 rs114101502 (OR = 1.33, 95 % CI: 1.11–1.59, P = 0.002), and one SNP in primary miRNA sequence (rs116159732 in miR-6826, OR = 0.74, 95 % CI: 0.63–0.89, P = 0.001) were found to have significant associations in both discovery and validation phases. In a subgroup analysis, two SNPs were associated with risk of estrogen receptor (ER)-negative breast cancer, and three SNPs were associated with risk of ER-positive breast cancer. Several variants in miRNA and miRNA biogenesis pathway genes were associated with breast cancer risk. Risk associations varied by ER status, suggesting potential new mechanisms in etiology.

Original languageEnglish (US)
Pages (from-to)1-15
Number of pages15
JournalHuman Genetics
DOIs
StateAccepted/In press - Jul 5 2016

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MicroRNAs
Breast Neoplasms
Genes
Odds Ratio
Single Nucleotide Polymorphism
Confidence Intervals
Estrogen Receptors
RNA Stability
Breast
Logistic Models

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Qian, F., Feng, Y., Zheng, Y., Ogundiran, T. O., Ojengbede, O., Zheng, W., ... Huo, D. (Accepted/In press). Genetic variants in microRNA and microRNA biogenesis pathway genes and breast cancer risk among women of African ancestry. Human Genetics, 1-15. https://doi.org/10.1007/s00439-016-1707-1

Genetic variants in microRNA and microRNA biogenesis pathway genes and breast cancer risk among women of African ancestry. / Qian, Frank; Feng, Ye; Zheng, Yonglan; Ogundiran, Temidayo O.; Ojengbede, Oladosu; Zheng, Wei; Blot, William; Ambrosone, Christine B.; John, Esther M.; Bernstein, Leslie; Hu, Jennifer; Ziegler, Regina G.; Nyante, Sarah; Bandera, Elisa V.; Ingles, Sue A.; Press, Michael F.; Nathanson, Katherine L.; Hennis, Anselm; Nemesure, Barbara; Ambs, Stefan; Kolonel, Laurence N.; Olopade, Olufunmilayo I.; Haiman, Christopher A.; Huo, Dezheng.

In: Human Genetics, 05.07.2016, p. 1-15.

Research output: Contribution to journalArticle

Qian, F, Feng, Y, Zheng, Y, Ogundiran, TO, Ojengbede, O, Zheng, W, Blot, W, Ambrosone, CB, John, EM, Bernstein, L, Hu, J, Ziegler, RG, Nyante, S, Bandera, EV, Ingles, SA, Press, MF, Nathanson, KL, Hennis, A, Nemesure, B, Ambs, S, Kolonel, LN, Olopade, OI, Haiman, CA & Huo, D 2016, 'Genetic variants in microRNA and microRNA biogenesis pathway genes and breast cancer risk among women of African ancestry', Human Genetics, pp. 1-15. https://doi.org/10.1007/s00439-016-1707-1
Qian, Frank ; Feng, Ye ; Zheng, Yonglan ; Ogundiran, Temidayo O. ; Ojengbede, Oladosu ; Zheng, Wei ; Blot, William ; Ambrosone, Christine B. ; John, Esther M. ; Bernstein, Leslie ; Hu, Jennifer ; Ziegler, Regina G. ; Nyante, Sarah ; Bandera, Elisa V. ; Ingles, Sue A. ; Press, Michael F. ; Nathanson, Katherine L. ; Hennis, Anselm ; Nemesure, Barbara ; Ambs, Stefan ; Kolonel, Laurence N. ; Olopade, Olufunmilayo I. ; Haiman, Christopher A. ; Huo, Dezheng. / Genetic variants in microRNA and microRNA biogenesis pathway genes and breast cancer risk among women of African ancestry. In: Human Genetics. 2016 ; pp. 1-15.
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abstract = "MicroRNAs (miRNA) regulate breast biology by binding to specific RNA sequences, leading to RNA degradation and inhibition of translation of their target genes. While germline genetic variations may disrupt some of these interactions between miRNAs and their targets, studies assessing the relationship between genetic variations in the miRNA network and breast cancer risk are still limited, particularly among women of African ancestry. We systematically put together a list of 822 and 10,468 genetic variants among primary miRNA sequences and 38 genes in the miRNA biogenesis pathway, respectively; and examined their association with breast cancer risk in the ROOT consortium which includes women of African ancestry. Findings were replicated in an independent consortium. Logistic regression was used to estimate the odds ratio (OR) and 95 {\%} confidence intervals (CI). For overall breast cancer risk, three single-nucleotide polymorphisms (SNPs) in miRNA biogenesis genes DROSHA rs78393591 (OR = 0.69, 95 {\%} CI: 0.55–0.88, P = 0.003), ESR1 rs523736 (OR = 0.88, 95 {\%} CI: 0.82–0.95, P = 3.99 × 10−4), and ZCCHC11 rs114101502 (OR = 1.33, 95 {\%} CI: 1.11–1.59, P = 0.002), and one SNP in primary miRNA sequence (rs116159732 in miR-6826, OR = 0.74, 95 {\%} CI: 0.63–0.89, P = 0.001) were found to have significant associations in both discovery and validation phases. In a subgroup analysis, two SNPs were associated with risk of estrogen receptor (ER)-negative breast cancer, and three SNPs were associated with risk of ER-positive breast cancer. Several variants in miRNA and miRNA biogenesis pathway genes were associated with breast cancer risk. Risk associations varied by ER status, suggesting potential new mechanisms in etiology.",
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AU - Qian, Frank

AU - Feng, Ye

AU - Zheng, Yonglan

AU - Ogundiran, Temidayo O.

AU - Ojengbede, Oladosu

AU - Zheng, Wei

AU - Blot, William

AU - Ambrosone, Christine B.

AU - John, Esther M.

AU - Bernstein, Leslie

AU - Hu, Jennifer

AU - Ziegler, Regina G.

AU - Nyante, Sarah

AU - Bandera, Elisa V.

AU - Ingles, Sue A.

AU - Press, Michael F.

AU - Nathanson, Katherine L.

AU - Hennis, Anselm

AU - Nemesure, Barbara

AU - Ambs, Stefan

AU - Kolonel, Laurence N.

AU - Olopade, Olufunmilayo I.

AU - Haiman, Christopher A.

AU - Huo, Dezheng

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