Investigation of the Interplay between Circulating Lipids and IGF-I and Relevance to Breast Cancer Risk: An Observational and Mendelian Randomization Study

Circulating lipids and insulin-like growth factor 1 (IGF-I) have been reliably associated with breast cancer. Observational studies suggest an interplay between lipids and IGF-I, however, whether these relationships are causal and if pathways from these phenotypes to breast cancer overlap is unclear...

Celý popis

Uloženo v:
Podrobná bibliografie
Vydáno v:Cancer epidemiology, biomarkers & prevention Ročník 30; číslo 12; s. 2207
Hlavní autoři: Tan, Vanessa Y, Bull, Caroline J, Biernacka, Kalina M, Teumer, Alexander, Richardson, Tom G, Sanderson, Eleanor, Corbin, Laura J, Dudding, Tom, Qi, Qibin, Kaplan, Robert C, Rotter, Jerome I, Friedrich, Nele, Völker, Uwe, Mayerle, Julia, Perks, Claire M, Holly, Jeff M P, Timpson, Nicholas J
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 01.12.2021
Témata:
ISSN:1538-7755, 1538-7755
On-line přístup:Zjistit podrobnosti o přístupu
Tagy: Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
Abstract Circulating lipids and insulin-like growth factor 1 (IGF-I) have been reliably associated with breast cancer. Observational studies suggest an interplay between lipids and IGF-I, however, whether these relationships are causal and if pathways from these phenotypes to breast cancer overlap is unclear. Mendelian randomization (MR) was conducted to estimate the relationship between lipids or IGF-I and breast cancer risk using genetic summary statistics for lipids (low-density lipoprotein cholesterol, LDL-C; high-density lipoprotein cholesterol, HDL-C; triglycerides, TGs), IGF-I and breast cancer from GLGC/UKBB ( = 239,119), CHARGE/UKBB ( = 252,547), and Breast Cancer Association Consortium ( = 247,173), respectively. Cross-sectional observational and MR analyses were conducted to assess the bi-directional relationship between lipids and IGF-I in SHIP ( = 3,812) and UKBB ( = 422,389), and using genetic summary statistics from GLGC ( = 188,577) and CHARGE/UKBB ( = 469,872). In multivariable MR (MVMR) analyses, the OR for breast cancer per 1-SD increase in HDL-C and TG was 1.08 [95% confidence interval (CI), 1.04-1.13] and 0.94 (95% CI, 0.89-0.98), respectively. The OR for breast cancer per 1-SD increase in IGF-I was 1.09 (95% CI, 1.04-1.15). MR analyses suggested a bi-directional TG-IGF-I relationship (TG-IGF-I per 1-SD: -0.13; 95% CI, -0.23 to -0.04; and IGF-I-TG per 1-SD: -0.11; 95% CI, -0.18 to -0.05). There was little evidence for a causal relationship between HDL-C and LDL-C with IGF-I. In MVMR analyses, associations of TG or IGF-I with breast cancer were robust to adjustment for IGF-I or TG, respectively. Our findings suggest a causal role of HDL-C, TG, and IGF-I in breast cancer. Observational and MR analyses support an interplay between IGF-I and TG; however, MVMR estimates suggest that TG and IGF-I may act independently to influence breast cancer. Our findings should be considered in the development of prevention strategies for breast cancer, where interventions are known to modify circulating lipids and IGF-I.
AbstractList Circulating lipids and insulin-like growth factor 1 (IGF-I) have been reliably associated with breast cancer. Observational studies suggest an interplay between lipids and IGF-I, however, whether these relationships are causal and if pathways from these phenotypes to breast cancer overlap is unclear. Mendelian randomization (MR) was conducted to estimate the relationship between lipids or IGF-I and breast cancer risk using genetic summary statistics for lipids (low-density lipoprotein cholesterol, LDL-C; high-density lipoprotein cholesterol, HDL-C; triglycerides, TGs), IGF-I and breast cancer from GLGC/UKBB ( = 239,119), CHARGE/UKBB ( = 252,547), and Breast Cancer Association Consortium ( = 247,173), respectively. Cross-sectional observational and MR analyses were conducted to assess the bi-directional relationship between lipids and IGF-I in SHIP ( = 3,812) and UKBB ( = 422,389), and using genetic summary statistics from GLGC ( = 188,577) and CHARGE/UKBB ( = 469,872). In multivariable MR (MVMR) analyses, the OR for breast cancer per 1-SD increase in HDL-C and TG was 1.08 [95% confidence interval (CI), 1.04-1.13] and 0.94 (95% CI, 0.89-0.98), respectively. The OR for breast cancer per 1-SD increase in IGF-I was 1.09 (95% CI, 1.04-1.15). MR analyses suggested a bi-directional TG-IGF-I relationship (TG-IGF-I per 1-SD: -0.13; 95% CI, -0.23 to -0.04; and IGF-I-TG per 1-SD: -0.11; 95% CI, -0.18 to -0.05). There was little evidence for a causal relationship between HDL-C and LDL-C with IGF-I. In MVMR analyses, associations of TG or IGF-I with breast cancer were robust to adjustment for IGF-I or TG, respectively. Our findings suggest a causal role of HDL-C, TG, and IGF-I in breast cancer. Observational and MR analyses support an interplay between IGF-I and TG; however, MVMR estimates suggest that TG and IGF-I may act independently to influence breast cancer. Our findings should be considered in the development of prevention strategies for breast cancer, where interventions are known to modify circulating lipids and IGF-I.
Circulating lipids and insulin-like growth factor 1 (IGF-I) have been reliably associated with breast cancer. Observational studies suggest an interplay between lipids and IGF-I, however, whether these relationships are causal and if pathways from these phenotypes to breast cancer overlap is unclear.BACKGROUNDCirculating lipids and insulin-like growth factor 1 (IGF-I) have been reliably associated with breast cancer. Observational studies suggest an interplay between lipids and IGF-I, however, whether these relationships are causal and if pathways from these phenotypes to breast cancer overlap is unclear.Mendelian randomization (MR) was conducted to estimate the relationship between lipids or IGF-I and breast cancer risk using genetic summary statistics for lipids (low-density lipoprotein cholesterol, LDL-C; high-density lipoprotein cholesterol, HDL-C; triglycerides, TGs), IGF-I and breast cancer from GLGC/UKBB (N = 239,119), CHARGE/UKBB (N = 252,547), and Breast Cancer Association Consortium (N = 247,173), respectively. Cross-sectional observational and MR analyses were conducted to assess the bi-directional relationship between lipids and IGF-I in SHIP (N = 3,812) and UKBB (N = 422,389), and using genetic summary statistics from GLGC (N = 188,577) and CHARGE/UKBB (N = 469,872).METHODSMendelian randomization (MR) was conducted to estimate the relationship between lipids or IGF-I and breast cancer risk using genetic summary statistics for lipids (low-density lipoprotein cholesterol, LDL-C; high-density lipoprotein cholesterol, HDL-C; triglycerides, TGs), IGF-I and breast cancer from GLGC/UKBB (N = 239,119), CHARGE/UKBB (N = 252,547), and Breast Cancer Association Consortium (N = 247,173), respectively. Cross-sectional observational and MR analyses were conducted to assess the bi-directional relationship between lipids and IGF-I in SHIP (N = 3,812) and UKBB (N = 422,389), and using genetic summary statistics from GLGC (N = 188,577) and CHARGE/UKBB (N = 469,872).In multivariable MR (MVMR) analyses, the OR for breast cancer per 1-SD increase in HDL-C and TG was 1.08 [95% confidence interval (CI), 1.04-1.13] and 0.94 (95% CI, 0.89-0.98), respectively. The OR for breast cancer per 1-SD increase in IGF-I was 1.09 (95% CI, 1.04-1.15). MR analyses suggested a bi-directional TG-IGF-I relationship (TG-IGF-I β per 1-SD: -0.13; 95% CI, -0.23 to -0.04; and IGF-I-TG β per 1-SD: -0.11; 95% CI, -0.18 to -0.05). There was little evidence for a causal relationship between HDL-C and LDL-C with IGF-I. In MVMR analyses, associations of TG or IGF-I with breast cancer were robust to adjustment for IGF-I or TG, respectively.RESULTSIn multivariable MR (MVMR) analyses, the OR for breast cancer per 1-SD increase in HDL-C and TG was 1.08 [95% confidence interval (CI), 1.04-1.13] and 0.94 (95% CI, 0.89-0.98), respectively. The OR for breast cancer per 1-SD increase in IGF-I was 1.09 (95% CI, 1.04-1.15). MR analyses suggested a bi-directional TG-IGF-I relationship (TG-IGF-I β per 1-SD: -0.13; 95% CI, -0.23 to -0.04; and IGF-I-TG β per 1-SD: -0.11; 95% CI, -0.18 to -0.05). There was little evidence for a causal relationship between HDL-C and LDL-C with IGF-I. In MVMR analyses, associations of TG or IGF-I with breast cancer were robust to adjustment for IGF-I or TG, respectively.Our findings suggest a causal role of HDL-C, TG, and IGF-I in breast cancer. Observational and MR analyses support an interplay between IGF-I and TG; however, MVMR estimates suggest that TG and IGF-I may act independently to influence breast cancer.CONCLUSIONSOur findings suggest a causal role of HDL-C, TG, and IGF-I in breast cancer. Observational and MR analyses support an interplay between IGF-I and TG; however, MVMR estimates suggest that TG and IGF-I may act independently to influence breast cancer.Our findings should be considered in the development of prevention strategies for breast cancer, where interventions are known to modify circulating lipids and IGF-I.IMPACTOur findings should be considered in the development of prevention strategies for breast cancer, where interventions are known to modify circulating lipids and IGF-I.
Author Bull, Caroline J
Dudding, Tom
Timpson, Nicholas J
Perks, Claire M
Rotter, Jerome I
Biernacka, Kalina M
Friedrich, Nele
Teumer, Alexander
Sanderson, Eleanor
Qi, Qibin
Mayerle, Julia
Holly, Jeff M P
Kaplan, Robert C
Tan, Vanessa Y
Richardson, Tom G
Völker, Uwe
Corbin, Laura J
Author_xml – sequence: 1
  givenname: Vanessa Y
  orcidid: 0000-0001-7938-127X
  surname: Tan
  fullname: Tan, Vanessa Y
  organization: Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
– sequence: 2
  givenname: Caroline J
  orcidid: 0000-0002-2176-5120
  surname: Bull
  fullname: Bull, Caroline J
  organization: Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
– sequence: 3
  givenname: Kalina M
  orcidid: 0000-0001-6344-7449
  surname: Biernacka
  fullname: Biernacka, Kalina M
  organization: IGFs & Metabolic Endocrinology Group, School of Translational Health Sciences, Learning & Research Building, Southmead Hospital, Bristol, United Kingdom
– sequence: 4
  givenname: Alexander
  orcidid: 0000-0002-8309-094X
  surname: Teumer
  fullname: Teumer, Alexander
  organization: Department of Population Medicine and Lifestyle Diseases Prevention, Medical University of Bialystok, Bialystok, Poland
– sequence: 5
  givenname: Tom G
  orcidid: 0000-0002-7918-2040
  surname: Richardson
  fullname: Richardson, Tom G
  organization: Novo Nordisk Research Centre, Headington, Oxford, United Kingdom
– sequence: 6
  givenname: Eleanor
  surname: Sanderson
  fullname: Sanderson, Eleanor
  organization: Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
– sequence: 7
  givenname: Laura J
  orcidid: 0000-0002-4032-9500
  surname: Corbin
  fullname: Corbin, Laura J
  organization: Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
– sequence: 8
  givenname: Tom
  orcidid: 0000-0003-3756-040X
  surname: Dudding
  fullname: Dudding, Tom
  organization: Bristol Dental School, University of Bristol, Bristol, United Kingdom
– sequence: 9
  givenname: Qibin
  surname: Qi
  fullname: Qi, Qibin
  organization: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York
– sequence: 10
  givenname: Robert C
  surname: Kaplan
  fullname: Kaplan, Robert C
  organization: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
– sequence: 11
  givenname: Jerome I
  orcidid: 0000-0001-7191-1723
  surname: Rotter
  fullname: Rotter, Jerome I
  organization: The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California
– sequence: 12
  givenname: Nele
  surname: Friedrich
  fullname: Friedrich, Nele
  organization: Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany
– sequence: 13
  givenname: Uwe
  surname: Völker
  fullname: Völker, Uwe
  organization: Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany
– sequence: 14
  givenname: Julia
  surname: Mayerle
  fullname: Mayerle, Julia
  organization: Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
– sequence: 15
  givenname: Claire M
  orcidid: 0000-0003-1562-891X
  surname: Perks
  fullname: Perks, Claire M
  organization: IGFs & Metabolic Endocrinology Group, School of Translational Health Sciences, Learning & Research Building, Southmead Hospital, Bristol, United Kingdom
– sequence: 16
  givenname: Jeff M P
  surname: Holly
  fullname: Holly, Jeff M P
  organization: IGFs & Metabolic Endocrinology Group, School of Translational Health Sciences, Learning & Research Building, Southmead Hospital, Bristol, United Kingdom
– sequence: 17
  givenname: Nicholas J
  surname: Timpson
  fullname: Timpson, Nicholas J
  email: N.J.Timpson@bristol.ac.uk
  organization: Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
BackLink https://www.ncbi.nlm.nih.gov/pubmed/34583967$$D View this record in MEDLINE/PubMed
BookMark eNpNkM1OwzAQhC0Eovw9AshHLgHb6doOt1LxE6moqMC5cpwNGFKnxE5ReRVellKKxGlnpG93R7NPtn3jkZBjzs44B33OGUCSZRLOru7zRPCEpRy2yB6HVCdKAWz_0z2yH8IrY0xlALukl_ZBp5lUe-Qr9wsM0T2b6BpPm4rGF6S5j9jOa7OkBcYPRE-HrrVdvYL8Mx25uSsDNb6k-c11kq_VBGtcGG-RxoZetmhCpMMf39KJC28XdODpuAjYLtafTL3eukNfYu2Mp5OVbWbu8zfHQ-zK5SHZqUwd8GgzD8jT9dXj8DYZjW_y4WCUWGAyJpVCYCVqzTiXtsgKY7lmwkhVCZRGS5SVEawEKCzPRFX008r2rZAiU0wLIw7I6e_dedu8d6s2pjMXLNa18dh0YSpAKZUyncIKPdmgXTHDcjpv3cy0y-lfoeIbPxd8lQ
CitedBy_id crossref_primary_10_1186_s12937_025_01077_w
crossref_primary_10_1016_j_bbcan_2022_188800
crossref_primary_10_1186_s12944_024_02103_2
crossref_primary_10_3390_ijms24054974
crossref_primary_10_1093_eurheartj_ehac822
crossref_primary_10_1007_s13668_023_00457_0
crossref_primary_10_1038_s41598_023_41130_4
crossref_primary_10_1186_s12933_022_01714_2
ContentType Journal Article
Copyright 2021 The Authors; Published by the American Association for Cancer Research.
Copyright_xml – notice: 2021 The Authors; Published by the American Association for Cancer Research.
DBID CGR
CUY
CVF
ECM
EIF
NPM
7X8
DOI 10.1158/1055-9965.EPI-21-0315
DatabaseName Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
MEDLINE - Academic
DatabaseTitle MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
MEDLINE - Academic
DatabaseTitleList MEDLINE
MEDLINE - Academic
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: 7X8
  name: MEDLINE - Academic
  url: https://search.proquest.com/medline
  sourceTypes: Aggregation Database
DeliveryMethod no_fulltext_linktorsrc
Discipline Medicine
EISSN 1538-7755
ExternalDocumentID 34583967
Genre Research Support, Non-U.S. Gov't
Journal Article
Observational Study
Research Support, N.I.H., Extramural
GrantInformation_xml – fundername: Cancer Research UK
  grantid: A19169
– fundername: Cancer Research UK
  grantid: C18281/A29019
– fundername: NCATS NIH HHS
  grantid: UL1 TR001881
– fundername: NHLBI NIH HHS
  grantid: K01 HL129892
– fundername: Cancer Research UK
  grantid: 19169
– fundername: NHLBI NIH HHS
  grantid: R01 HL105756
– fundername: Cancer Research UK
  grantid: 29019
– fundername: Wellcome Trust
  grantid: 202802/Z/16/Z
– fundername: Wellcome Trust
  grantid: 202802
– fundername: Medical Research Council
  grantid: MC_UU_12013/3
GroupedDBID ---
.55
18M
29B
2FS
2WC
34G
39C
3O-
53G
5GY
5VS
6J9
AAFWJ
ABOCM
ACPRK
ADBBV
ADCOW
AENEX
AFHIN
AFRAH
AI.
ALMA_UNASSIGNED_HOLDINGS
BR6
BTFSW
C1A
CGR
CS3
CUY
CVF
DIK
DU5
E3Z
EBS
ECM
EIF
EJD
F5P
FRP
H13
H~9
IH2
KQ8
L7B
NPM
OK1
P2P
PQQKQ
QTD
RCR
RHI
SJN
UDS
VH1
W8F
WHG
WOQ
X7M
ZXP
7X8
ID FETCH-LOGICAL-c506t-f7e50de880116cb9bac1802a67f2e6a86e6fa20d55bc192fb43fc4c26297082a2
IEDL.DBID 7X8
ISICitedReferencesCount 9
ISICitedReferencesURI http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000728190200001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN 1538-7755
IngestDate Thu Jul 10 18:20:01 EDT 2025
Mon Jul 21 06:03:13 EDT 2025
IsDoiOpenAccess false
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 12
Language English
License 2021 The Authors; Published by the American Association for Cancer Research.
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c506t-f7e50de880116cb9bac1802a67f2e6a86e6fa20d55bc192fb43fc4c26297082a2
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ObjectType-Undefined-3
ORCID 0000-0002-7918-2040
0000-0002-2176-5120
0000-0001-6344-7449
0000-0002-4032-9500
0000-0001-7938-127X
0000-0003-1562-891X
0000-0003-3756-040X
0000-0001-7191-1723
0000-0002-8309-094X
OpenAccessLink https://doi.org/10.1158/1055-9965.epi-21-0315
PMID 34583967
PQID 2577730835
PQPubID 23479
ParticipantIDs proquest_miscellaneous_2577730835
pubmed_primary_34583967
PublicationCentury 2000
PublicationDate 2021-12-01
PublicationDateYYYYMMDD 2021-12-01
PublicationDate_xml – month: 12
  year: 2021
  text: 2021-12-01
  day: 01
PublicationDecade 2020
PublicationPlace United States
PublicationPlace_xml – name: United States
PublicationTitle Cancer epidemiology, biomarkers & prevention
PublicationTitleAlternate Cancer Epidemiol Biomarkers Prev
PublicationYear 2021
SSID ssj0007955
Score 2.4349806
Snippet Circulating lipids and insulin-like growth factor 1 (IGF-I) have been reliably associated with breast cancer. Observational studies suggest an interplay...
SourceID proquest
pubmed
SourceType Aggregation Database
Index Database
StartPage 2207
SubjectTerms Breast Neoplasms - blood
Breast Neoplasms - genetics
Causality
Cholesterol, HDL - blood
Cholesterol, LDL - blood
Cross-Sectional Studies
Female
Genome-Wide Association Study
Humans
Insulin-Like Growth Factor I - genetics
Mendelian Randomization Analysis
Triglycerides - blood
Title Investigation of the Interplay between Circulating Lipids and IGF-I and Relevance to Breast Cancer Risk: An Observational and Mendelian Randomization Study
URI https://www.ncbi.nlm.nih.gov/pubmed/34583967
https://www.proquest.com/docview/2577730835
Volume 30
WOSCitedRecordID wos000728190200001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText
inHoldings 1
isFullTextHit
isPrint
link http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1Rb9MwELaAoWkvjI1tjMF0SHs1S9zYTvaCRrWySmupKkB9qxzbmSogKU2Z1N_Cn-XOdRkvSEi8JPGDJcs5X77cfXcfY2fWUr2kzHiptMIflCLnuROap84Zl2cdlwQdss83ejjMJ5NiFANubaRVbnxicNSusRQjP0fT0miNCBjezr9zUo2i7GqU0HjItjoIZciq9eS-W7guguppONRaSxkreFKZn5MuJEesL99cjfpcEK0olX9HmeFr09v933U-ZU8izoTLtWHssQe-3mfbg5hJf8Z-_tFgo6mhqQCRIKwpiF_NCiJ_C7qzhQ0KX_UtkM61a8HUDvrve7wfnsZUoE6mA8sG3hHFfQldGi9gPGu_XMBlDR_K37FfXBPNGlDknSIsMMZh8y1WgwLRGlcH7FPv6mP3mkehBm5lopa80l4mzqMrSFNly6I0lhrLGaUr4ZXJlVeVEYmTsrSIKKsy61Q2s0KJQiMEMeKQPaqb2j9nkEnnqKU9ArsqK_PEFBYBqcJ5Hm9eHLPXm22f4kGg7IapffOjnd5v_DE7Wr-76XzdsWPaoexwofSLf5h9wnYE8VYCZeUl26rQDfhX7LG9W87axWmwMLwOR4Nfjl3ayA
linkProvider ProQuest
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Investigation+of+the+Interplay+between+Circulating+Lipids+and+IGF-I+and+Relevance+to+Breast+Cancer+Risk%3A+An+Observational+and+Mendelian+Randomization+Study&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention&rft.au=Tan%2C+Vanessa+Y&rft.au=Bull%2C+Caroline+J&rft.au=Biernacka%2C+Kalina+M&rft.au=Teumer%2C+Alexander&rft.date=2021-12-01&rft.eissn=1538-7755&rft.volume=30&rft.issue=12&rft.spage=2207&rft_id=info:doi/10.1158%2F1055-9965.EPI-21-0315&rft_id=info%3Apmid%2F34583967&rft_id=info%3Apmid%2F34583967&rft.externalDocID=34583967
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1538-7755&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1538-7755&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1538-7755&client=summon