MicroRNA related polymorphisms and breast cancer risk

Sofia Khan; Dario Greco; Kyriaki Michailidou; Roger L Milne; Taru A Muranen; Tuomas Heikkinen; Kirsimari Aaltonen; Joe Dennis; Manjeet K Bolla; Jianjun Liu; Per Hall; Astrid Irwanto; Keith Humphreys; Jingmei Li; Kamila Czene; Jenny Chang-Claude; Rebecca Hein; Anja Rudolph; Petra Seibold; Dieter Flesch-Janys; Olivia Fletcher; Julian Peto; Isabel dos Santos Silva; Nichola Johnson; Lorna Gibson; Zoe Aitken; John L Hopper; Helen Tsimiklis; Minh Bui; Enes Makalic; Daniel F Schmidt; Melissa C Southey; Carmel Apicella; Jennifer Stone; Quinten Waisfisz; Hanne Meijers-Heijboer; Muriel A Adank; Rob B van der Luijt; Alfons Meindl; Rita K Schmutzler; Bertram Müller-Myhsok; Peter Lichtner; Clare Turnbull; Nazneen Rahman; Stephen J Chanock; David J Hunter; Angela Cox; Simon S Cross; Malcolm W R Reed; Jonine Figueroa; kConFab Investigators; Ian Tomlinson

doi:10.1371/journal.pone.0109973

MicroRNA related polymorphisms and breast cancer risk

Sofia Khan, Dario Greco, Kyriaki Michailidou, Roger L Milne, Taru A Muranen, Tuomas Heikkinen, Kirsimari Aaltonen, Joe Dennis, Manjeet K Bolla, Jianjun Liu, Per Hall, Astrid Irwanto, Keith Humphreys, Jingmei Li, Kamila Czene, Jenny Chang-Claude, Rebecca Hein, Anja Rudolph, Petra Seibold, Dieter Flesch-JanysOlivia Fletcher, Julian Peto, Isabel dos Santos Silva, Nichola Johnson, Lorna Gibson, Zoe Aitken, John L Hopper, Helen Tsimiklis, Minh Bui, Enes Makalic, Daniel F Schmidt, Melissa C Southey, Carmel Apicella, Jennifer Stone, Quinten Waisfisz, Hanne Meijers-Heijboer, Muriel A Adank, Rob B van der Luijt, Alfons Meindl, Rita K Schmutzler, Bertram Müller-Myhsok, Peter Lichtner, Clare Turnbull, Nazneen Rahman, Stephen J Chanock, David J Hunter, Angela Cox, Simon S Cross, Malcolm W R Reed, Jonine Figueroa, kConFab Investigators, Ian Tomlinson

Research output: Contribution to journal › Article › peer-review

Abstract

Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88-0.96), rs1052532 (OR 0.97; 95% CI: 0.95-0.99), rs10719 (OR 0.97; 95% CI: 0.94-0.99), rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI: 1.01-1.05) located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects.

Original language	English
Pages (from-to)	e109973
Journal	PLoS ONE
Volume	9
Issue number	11
DOIs	https://doi.org/10.1371/journal.pone.0109973
Publication status	Published - 2014

Keywords

3' Untranslated Regions
Binding Sites
Breast Neoplasms
Case-Control Studies
Chromosome Mapping
Computational Biology
Female
Genome-Wide Association Study
Genotype
Humans
MicroRNAs
Polymorphism, Single Nucleotide
Receptors, Estrogen

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10.1371/journal.pone.0109973

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Khan, S., Greco, D., Michailidou, K., Milne, R. L., Muranen, T. A., Heikkinen, T., Aaltonen, K., Dennis, J., Bolla, M. K., Liu, J., Hall, P., Irwanto, A., Humphreys, K., Li, J., Czene, K., Chang-Claude, J., Hein, R., Rudolph, A., Seibold, P., ... Tomlinson, I. (2014). MicroRNA related polymorphisms and breast cancer risk. PLoS ONE, 9(11), e109973. https://doi.org/10.1371/journal.pone.0109973

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title = "MicroRNA related polymorphisms and breast cancer risk",

abstract = "Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88-0.96), rs1052532 (OR 0.97; 95% CI: 0.95-0.99), rs10719 (OR 0.97; 95% CI: 0.94-0.99), rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI: 1.01-1.05) located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects.",

keywords = "3' Untranslated Regions, Binding Sites, Breast Neoplasms, Case-Control Studies, Chromosome Mapping, Computational Biology, Female, Genome-Wide Association Study, Genotype, Humans, MicroRNAs, Polymorphism, Single Nucleotide, Receptors, Estrogen",

author = "Sofia Khan and Dario Greco and Kyriaki Michailidou and Milne, {Roger L} and Muranen, {Taru A} and Tuomas Heikkinen and Kirsimari Aaltonen and Joe Dennis and Bolla, {Manjeet K} and Jianjun Liu and Per Hall and Astrid Irwanto and Keith Humphreys and Jingmei Li and Kamila Czene and Jenny Chang-Claude and Rebecca Hein and Anja Rudolph and Petra Seibold and Dieter Flesch-Janys and Olivia Fletcher and Julian Peto and {dos Santos Silva}, Isabel and Nichola Johnson and Lorna Gibson and Zoe Aitken and Hopper, {John L} and Helen Tsimiklis and Minh Bui and Enes Makalic and Schmidt, {Daniel F} and Southey, {Melissa C} and Carmel Apicella and Jennifer Stone and Quinten Waisfisz and Hanne Meijers-Heijboer and Adank, {Muriel A} and {van der Luijt}, {Rob B} and Alfons Meindl and Schmutzler, {Rita K} and Bertram M{\"u}ller-Myhsok and Peter Lichtner and Clare Turnbull and Nazneen Rahman and Chanock, {Stephen J} and Hunter, {David J} and Angela Cox and Cross, {Simon S} and Reed, {Malcolm W R} and Jonine Figueroa and {kConFab Investigators} and Ian Tomlinson",

year = "2014",

doi = "10.1371/journal.pone.0109973",

language = "English",

volume = "9",

pages = "e109973",

journal = "PLoS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "11",

}

Khan, S, Greco, D, Michailidou, K, Milne, RL, Muranen, TA, Heikkinen, T, Aaltonen, K, Dennis, J, Bolla, MK, Liu, J, Hall, P, Irwanto, A, Humphreys, K, Li, J, Czene, K, Chang-Claude, J, Hein, R, Rudolph, A, Seibold, P, Flesch-Janys, D, Fletcher, O, Peto, J, dos Santos Silva, I, Johnson, N, Gibson, L, Aitken, Z, Hopper, JL, Tsimiklis, H, Bui, M, Makalic, E, Schmidt, DF, Southey, MC, Apicella, C, Stone, J, Waisfisz, Q, Meijers-Heijboer, H, Adank, MA, van der Luijt, RB, Meindl, A, Schmutzler, RK, Müller-Myhsok, B, Lichtner, P, Turnbull, C, Rahman, N, Chanock, SJ, Hunter, DJ, Cox, A, Cross, SS, Reed, MWR, Figueroa, J, kConFab Investigators & Tomlinson, I 2014, 'MicroRNA related polymorphisms and breast cancer risk', PLoS ONE, vol. 9, no. 11, pp. e109973. https://doi.org/10.1371/journal.pone.0109973

TY - JOUR

T1 - MicroRNA related polymorphisms and breast cancer risk

AU - Khan, Sofia

AU - Greco, Dario

AU - Michailidou, Kyriaki

AU - Milne, Roger L

AU - Muranen, Taru A

AU - Heikkinen, Tuomas

AU - Aaltonen, Kirsimari

AU - Dennis, Joe

AU - Bolla, Manjeet K

AU - Liu, Jianjun

AU - Hall, Per

AU - Irwanto, Astrid

AU - Humphreys, Keith

AU - Li, Jingmei

AU - Czene, Kamila

AU - Chang-Claude, Jenny

AU - Hein, Rebecca

AU - Rudolph, Anja

AU - Seibold, Petra

AU - Flesch-Janys, Dieter

AU - Fletcher, Olivia

AU - Peto, Julian

AU - dos Santos Silva, Isabel

AU - Johnson, Nichola

AU - Gibson, Lorna

AU - Aitken, Zoe

AU - Hopper, John L

AU - Tsimiklis, Helen

AU - Bui, Minh

AU - Makalic, Enes

AU - Schmidt, Daniel F

AU - Southey, Melissa C

AU - Apicella, Carmel

AU - Stone, Jennifer

AU - Waisfisz, Quinten

AU - Meijers-Heijboer, Hanne

AU - Adank, Muriel A

AU - van der Luijt, Rob B

AU - Meindl, Alfons

AU - Schmutzler, Rita K

AU - Müller-Myhsok, Bertram

AU - Lichtner, Peter

AU - Turnbull, Clare

AU - Rahman, Nazneen

AU - Chanock, Stephen J

AU - Hunter, David J

AU - Cox, Angela

AU - Cross, Simon S

AU - Reed, Malcolm W R

AU - Figueroa, Jonine

AU - kConFab Investigators

AU - Tomlinson, Ian

PY - 2014

Y1 - 2014

N2 - Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88-0.96), rs1052532 (OR 0.97; 95% CI: 0.95-0.99), rs10719 (OR 0.97; 95% CI: 0.94-0.99), rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI: 1.01-1.05) located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects.

AB - Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88-0.96), rs1052532 (OR 0.97; 95% CI: 0.95-0.99), rs10719 (OR 0.97; 95% CI: 0.94-0.99), rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI: 1.01-1.05) located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects.

KW - 3' Untranslated Regions

KW - Binding Sites

KW - Breast Neoplasms

KW - Case-Control Studies

KW - Chromosome Mapping

KW - Computational Biology

KW - Female

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - MicroRNAs

KW - Polymorphism, Single Nucleotide

KW - Receptors, Estrogen

U2 - 10.1371/journal.pone.0109973

DO - 10.1371/journal.pone.0109973

M3 - Article

C2 - 25390939

VL - 9

SP - e109973

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 11

ER -

MicroRNA related polymorphisms and breast cancer risk

Abstract

Keywords

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