Genetic variation in stromal proteins decorin and lumican with breast cancer: Investigations in two case-control studies

Linda E. Kelemen, Fergus J Couch, Shahana Ahmed, Alison M. Dunning, Paul D P Pharoah, Douglas F. Easton, Zachary S. Fredericksen, Robert A. Vierkant, V. Shane Pankratz, Ellen L Goode, Christopher G. Scott, David N. Rider, Xianshu Wang, James R Cerhan, Celine M Vachon

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Abstract

Introduction: The stroma is the supportive framework of biologic tissue in the breast, consisting of various proteins such as the proteoglycans, decorin and lumican. Altered expression of decorin and lumican is associated with breast tumors. We hypothesized that genetic variation in the decorin (DCN) and lumican (LUM) genes may contribute to breast cancer.Methods: We investigated associations of 14 common polymorphisms in the DCN and LUM genes with 798 breast cancer cases and 843 controls from Mayo Clinic, MN, USA. One polymorphism per gene with the strongest risk association in the Mayo Clinic sample was genotyped in 4,470 breast cancer cases and 4,560 controls from East Anglia, England (Studies of Epidemiology and Risk Factors in Cancer Heredity (SEARCH)).Results: In the Mayo Clinic sample, six polymorphisms were associated with breast cancer risk (Ptrend ≤ 0.05). The association with LUM rs2268578, evaluated further in SEARCH, was positive, although the odds ratios (OR) were weaker and not statistically significant. ORs were 1.4 (95% confidence interval [CI], 1.1 to 1.8) for heterozygotes and 2.2 (95% CI, 1.1 to 4.3; P2 df = 0.002) for homozygotes in the Mayo Clinic sample, and were 1.1 (95% CI, 0.9 to 1.2) for heterozygotes and 1.4 (95% CI, 1.0 to 2.1; P2 df = 0.13) for homozygotes in the SEARCH sample. In combined analyses, the ORs were 1.1 (95% CI, 1.0 to 1.2) for heterozygotes and 1.6 (95% CI, 1.2 to 2.3; P2 df = 0.005) for homozygotes. Positive associations for this polymorphism were observed for estrogen receptor-positive tumors in both the Mayo Clinic sample (OR for heterozygotes = 1.5, 1.1 to 1.9 and OR for homozygotes = 2.5, 1.2 to 5.3;P2 df = 0.001) and the SEARCH sample (OR for heterozygotes = 1.0, 0.9 to 1.1 and OR for homozygotes = 1.6, 1.0 to 2.5; P2 df = 0.10). In combined analyses, the ORs were 1.1 (95% CI, 0.9 to 1.2) for heterozygotes and 1.9 (95% CI, 1.3 to 2.8; P2 df = 0.001) for homozygotes.Conclusions: Although LUM rs2268578 was associated with breast cancer in the Mayo Clinic study, particularly estrogen receptor-positive breast cancer, weaker and modest associations were observed in the SEARCH sample. These modest associations will require larger samples to adequately assess the importance of this polymorphism in breast cancer.

Original languageEnglish (US)
Article numberR98
JournalBreast Cancer Research
Volume10
Issue number6
DOIs
StatePublished - Nov 26 2008

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Decorin
Case-Control Studies
Homozygote
Heterozygote
Heredity
Confidence Intervals
Breast Neoplasms
Epidemiology
Odds Ratio
Proteins
Neoplasms
Estrogen Receptors
Genes
Lumican
England
Breast

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Genetic variation in stromal proteins decorin and lumican with breast cancer : Investigations in two case-control studies. / Kelemen, Linda E.; Couch, Fergus J; Ahmed, Shahana; Dunning, Alison M.; Pharoah, Paul D P; Easton, Douglas F.; Fredericksen, Zachary S.; Vierkant, Robert A.; Pankratz, V. Shane; Goode, Ellen L; Scott, Christopher G.; Rider, David N.; Wang, Xianshu; Cerhan, James R; Vachon, Celine M.

In: Breast Cancer Research, Vol. 10, No. 6, R98, 26.11.2008.

Research output: Contribution to journalArticle

Kelemen, LE, Couch, FJ, Ahmed, S, Dunning, AM, Pharoah, PDP, Easton, DF, Fredericksen, ZS, Vierkant, RA, Pankratz, VS, Goode, EL, Scott, CG, Rider, DN, Wang, X, Cerhan, JR & Vachon, CM 2008, 'Genetic variation in stromal proteins decorin and lumican with breast cancer: Investigations in two case-control studies', Breast Cancer Research, vol. 10, no. 6, R98. https://doi.org/10.1186/bcr2201
Kelemen, Linda E. ; Couch, Fergus J ; Ahmed, Shahana ; Dunning, Alison M. ; Pharoah, Paul D P ; Easton, Douglas F. ; Fredericksen, Zachary S. ; Vierkant, Robert A. ; Pankratz, V. Shane ; Goode, Ellen L ; Scott, Christopher G. ; Rider, David N. ; Wang, Xianshu ; Cerhan, James R ; Vachon, Celine M. / Genetic variation in stromal proteins decorin and lumican with breast cancer : Investigations in two case-control studies. In: Breast Cancer Research. 2008 ; Vol. 10, No. 6.
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title = "Genetic variation in stromal proteins decorin and lumican with breast cancer: Investigations in two case-control studies",
abstract = "Introduction: The stroma is the supportive framework of biologic tissue in the breast, consisting of various proteins such as the proteoglycans, decorin and lumican. Altered expression of decorin and lumican is associated with breast tumors. We hypothesized that genetic variation in the decorin (DCN) and lumican (LUM) genes may contribute to breast cancer.Methods: We investigated associations of 14 common polymorphisms in the DCN and LUM genes with 798 breast cancer cases and 843 controls from Mayo Clinic, MN, USA. One polymorphism per gene with the strongest risk association in the Mayo Clinic sample was genotyped in 4,470 breast cancer cases and 4,560 controls from East Anglia, England (Studies of Epidemiology and Risk Factors in Cancer Heredity (SEARCH)).Results: In the Mayo Clinic sample, six polymorphisms were associated with breast cancer risk (Ptrend ≤ 0.05). The association with LUM rs2268578, evaluated further in SEARCH, was positive, although the odds ratios (OR) were weaker and not statistically significant. ORs were 1.4 (95{\%} confidence interval [CI], 1.1 to 1.8) for heterozygotes and 2.2 (95{\%} CI, 1.1 to 4.3; P2 df = 0.002) for homozygotes in the Mayo Clinic sample, and were 1.1 (95{\%} CI, 0.9 to 1.2) for heterozygotes and 1.4 (95{\%} CI, 1.0 to 2.1; P2 df = 0.13) for homozygotes in the SEARCH sample. In combined analyses, the ORs were 1.1 (95{\%} CI, 1.0 to 1.2) for heterozygotes and 1.6 (95{\%} CI, 1.2 to 2.3; P2 df = 0.005) for homozygotes. Positive associations for this polymorphism were observed for estrogen receptor-positive tumors in both the Mayo Clinic sample (OR for heterozygotes = 1.5, 1.1 to 1.9 and OR for homozygotes = 2.5, 1.2 to 5.3;P2 df = 0.001) and the SEARCH sample (OR for heterozygotes = 1.0, 0.9 to 1.1 and OR for homozygotes = 1.6, 1.0 to 2.5; P2 df = 0.10). In combined analyses, the ORs were 1.1 (95{\%} CI, 0.9 to 1.2) for heterozygotes and 1.9 (95{\%} CI, 1.3 to 2.8; P2 df = 0.001) for homozygotes.Conclusions: Although LUM rs2268578 was associated with breast cancer in the Mayo Clinic study, particularly estrogen receptor-positive breast cancer, weaker and modest associations were observed in the SEARCH sample. These modest associations will require larger samples to adequately assess the importance of this polymorphism in breast cancer.",
author = "Kelemen, {Linda E.} and Couch, {Fergus J} and Shahana Ahmed and Dunning, {Alison M.} and Pharoah, {Paul D P} and Easton, {Douglas F.} and Fredericksen, {Zachary S.} and Vierkant, {Robert A.} and Pankratz, {V. Shane} and Goode, {Ellen L} and Scott, {Christopher G.} and Rider, {David N.} and Xianshu Wang and Cerhan, {James R} and Vachon, {Celine M}",
year = "2008",
month = "11",
day = "26",
doi = "10.1186/bcr2201",
language = "English (US)",
volume = "10",
journal = "Breast Cancer Research",
issn = "1465-5411",
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TY - JOUR

T1 - Genetic variation in stromal proteins decorin and lumican with breast cancer

T2 - Investigations in two case-control studies

AU - Kelemen, Linda E.

AU - Couch, Fergus J

AU - Ahmed, Shahana

AU - Dunning, Alison M.

AU - Pharoah, Paul D P

AU - Easton, Douglas F.

AU - Fredericksen, Zachary S.

AU - Vierkant, Robert A.

AU - Pankratz, V. Shane

AU - Goode, Ellen L

AU - Scott, Christopher G.

AU - Rider, David N.

AU - Wang, Xianshu

AU - Cerhan, James R

AU - Vachon, Celine M

PY - 2008/11/26

Y1 - 2008/11/26

N2 - Introduction: The stroma is the supportive framework of biologic tissue in the breast, consisting of various proteins such as the proteoglycans, decorin and lumican. Altered expression of decorin and lumican is associated with breast tumors. We hypothesized that genetic variation in the decorin (DCN) and lumican (LUM) genes may contribute to breast cancer.Methods: We investigated associations of 14 common polymorphisms in the DCN and LUM genes with 798 breast cancer cases and 843 controls from Mayo Clinic, MN, USA. One polymorphism per gene with the strongest risk association in the Mayo Clinic sample was genotyped in 4,470 breast cancer cases and 4,560 controls from East Anglia, England (Studies of Epidemiology and Risk Factors in Cancer Heredity (SEARCH)).Results: In the Mayo Clinic sample, six polymorphisms were associated with breast cancer risk (Ptrend ≤ 0.05). The association with LUM rs2268578, evaluated further in SEARCH, was positive, although the odds ratios (OR) were weaker and not statistically significant. ORs were 1.4 (95% confidence interval [CI], 1.1 to 1.8) for heterozygotes and 2.2 (95% CI, 1.1 to 4.3; P2 df = 0.002) for homozygotes in the Mayo Clinic sample, and were 1.1 (95% CI, 0.9 to 1.2) for heterozygotes and 1.4 (95% CI, 1.0 to 2.1; P2 df = 0.13) for homozygotes in the SEARCH sample. In combined analyses, the ORs were 1.1 (95% CI, 1.0 to 1.2) for heterozygotes and 1.6 (95% CI, 1.2 to 2.3; P2 df = 0.005) for homozygotes. Positive associations for this polymorphism were observed for estrogen receptor-positive tumors in both the Mayo Clinic sample (OR for heterozygotes = 1.5, 1.1 to 1.9 and OR for homozygotes = 2.5, 1.2 to 5.3;P2 df = 0.001) and the SEARCH sample (OR for heterozygotes = 1.0, 0.9 to 1.1 and OR for homozygotes = 1.6, 1.0 to 2.5; P2 df = 0.10). In combined analyses, the ORs were 1.1 (95% CI, 0.9 to 1.2) for heterozygotes and 1.9 (95% CI, 1.3 to 2.8; P2 df = 0.001) for homozygotes.Conclusions: Although LUM rs2268578 was associated with breast cancer in the Mayo Clinic study, particularly estrogen receptor-positive breast cancer, weaker and modest associations were observed in the SEARCH sample. These modest associations will require larger samples to adequately assess the importance of this polymorphism in breast cancer.

AB - Introduction: The stroma is the supportive framework of biologic tissue in the breast, consisting of various proteins such as the proteoglycans, decorin and lumican. Altered expression of decorin and lumican is associated with breast tumors. We hypothesized that genetic variation in the decorin (DCN) and lumican (LUM) genes may contribute to breast cancer.Methods: We investigated associations of 14 common polymorphisms in the DCN and LUM genes with 798 breast cancer cases and 843 controls from Mayo Clinic, MN, USA. One polymorphism per gene with the strongest risk association in the Mayo Clinic sample was genotyped in 4,470 breast cancer cases and 4,560 controls from East Anglia, England (Studies of Epidemiology and Risk Factors in Cancer Heredity (SEARCH)).Results: In the Mayo Clinic sample, six polymorphisms were associated with breast cancer risk (Ptrend ≤ 0.05). The association with LUM rs2268578, evaluated further in SEARCH, was positive, although the odds ratios (OR) were weaker and not statistically significant. ORs were 1.4 (95% confidence interval [CI], 1.1 to 1.8) for heterozygotes and 2.2 (95% CI, 1.1 to 4.3; P2 df = 0.002) for homozygotes in the Mayo Clinic sample, and were 1.1 (95% CI, 0.9 to 1.2) for heterozygotes and 1.4 (95% CI, 1.0 to 2.1; P2 df = 0.13) for homozygotes in the SEARCH sample. In combined analyses, the ORs were 1.1 (95% CI, 1.0 to 1.2) for heterozygotes and 1.6 (95% CI, 1.2 to 2.3; P2 df = 0.005) for homozygotes. Positive associations for this polymorphism were observed for estrogen receptor-positive tumors in both the Mayo Clinic sample (OR for heterozygotes = 1.5, 1.1 to 1.9 and OR for homozygotes = 2.5, 1.2 to 5.3;P2 df = 0.001) and the SEARCH sample (OR for heterozygotes = 1.0, 0.9 to 1.1 and OR for homozygotes = 1.6, 1.0 to 2.5; P2 df = 0.10). In combined analyses, the ORs were 1.1 (95% CI, 0.9 to 1.2) for heterozygotes and 1.9 (95% CI, 1.3 to 2.8; P2 df = 0.001) for homozygotes.Conclusions: Although LUM rs2268578 was associated with breast cancer in the Mayo Clinic study, particularly estrogen receptor-positive breast cancer, weaker and modest associations were observed in the SEARCH sample. These modest associations will require larger samples to adequately assess the importance of this polymorphism in breast cancer.

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