Int7G24A Variant of Transforming Growth Factor-β Receptor Type I is Associated with Invasive Breast Cancer

Taiping Chen; Chad R. Jackson; Andrew Link; Michael P. Markey; Bruce M. Colligan; Larry E. Douglass; Jackson O. Pemberton; James A. Deddens; Jeremy R. Graff; Julia Carter

doi:10.1158/1078-0432.CCR-05-1518

Int7G24A Variant of Transforming Growth Factor-β Receptor Type I is Associated with Invasive Breast Cancer

Taiping Chen, Chad R. Jackson, Andrew Link, Michael P. Markey, Bruce M. Colligan, Larry E. Douglass, Jackson O. Pemberton, James A. Deddens, Jeremy R. Graff, Julia Carter

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

Abstract

Purpose: The transforming growth factor-β (TGF-β) signaling pathway has been frequently implicated in breast cancer. An intronic variant ( Int7G24A ) of TGF-β receptor type I ( TGFBR1 ) is associated with kidney and bladder cancers in our recent study. We hypothesize that this germline variant may be involved in development and progression of breast cancer. Experimental Design: Case-control studies were designed from archived paraffin-embedded tissue specimens from the same geographic area with a homogenous ethnic population. We analyzed 223 patients (25 with preinvasive tumors and 198 with invasive and metastatic breast cancers) and 153 noncancer controls. The Int7G24A was identified by PCR-RFLP. Another germline deletion ( TGFBR1*6A ) and somatic mutations in the TGFBR1 were also analyzed by PCR and single-strand conformational polymorphism. Results: The Int7G24A allele was evident in 32% of patients with preinvasive neoplasms and 48% of patients with invasive breast cancers compared with 26% controls ( P = 0.00008). In addition, 11 (5.6%) homozygous Int7G24A carriers were found in patients with invasive breast cancers, whereas only 3 (2%) homozygous carriers were found in the control group. The TGFBR1*6A allele was not significantly associated with breast cancer patients and only one somatic mutation was found in 71 breast cancers. Conclusion: These data suggest that the germline Int7G24A variant may represent a risk factor for invasive breast cancer and a marker for breast cancer progression. A separate study with a larger sample size is warranted to validate the association of the Int7G24A with human breast cancer.

Original language	American English
Journal	Clinical Cancer Research
Volume	12
Issue number	2
DOIs	https://doi.org/10.1158/1078-0432.CCR-05-1518
State	Published - Jan 15 2006
Externally published	Yes

Disciplines

Biochemistry, Biophysics, and Structural Biology
Molecular Biology

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@article{b5c9723056ae4c64a3649982de67b924,

title = "Int7G24A Variant of Transforming Growth Factor-β Receptor Type I is Associated with Invasive Breast Cancer",

abstract = " Purpose: The transforming growth factor-β (TGF-β) signaling pathway has been frequently implicated in breast cancer. An intronic variant ( Int7G24A ) of TGF-β receptor type I ( TGFBR1 ) is associated with kidney and bladder cancers in our recent study. We hypothesize that this germline variant may be involved in development and progression of breast cancer. Experimental Design: Case-control studies were designed from archived paraffin-embedded tissue specimens from the same geographic area with a homogenous ethnic population. We analyzed 223 patients (25 with preinvasive tumors and 198 with invasive and metastatic breast cancers) and 153 noncancer controls. The Int7G24A was identified by PCR-RFLP. Another germline deletion ( TGFBR1*6A ) and somatic mutations in the TGFBR1 were also analyzed by PCR and single-strand conformational polymorphism. Results: The Int7G24A allele was evident in 32% of patients with preinvasive neoplasms and 48% of patients with invasive breast cancers compared with 26% controls ( P = 0.00008). In addition, 11 (5.6%) homozygous Int7G24A carriers were found in patients with invasive breast cancers, whereas only 3 (2%) homozygous carriers were found in the control group. The TGFBR1*6A allele was not significantly associated with breast cancer patients and only one somatic mutation was found in 71 breast cancers. Conclusion: These data suggest that the germline Int7G24A variant may represent a risk factor for invasive breast cancer and a marker for breast cancer progression. A separate study with a larger sample size is warranted to validate the association of the Int7G24A with human breast cancer. ",

author = "Taiping Chen and Jackson, {Chad R.} and Andrew Link and Markey, {Michael P.} and Colligan, {Bruce M.} and Douglass, {Larry E.} and Pemberton, {Jackson O.} and Deddens, {James A.} and Graff, {Jeremy R.} and Julia Carter",

year = "2006",

month = jan,

day = "15",

doi = "10.1158/1078-0432.CCR-05-1518",

language = "American English",

volume = "12",

journal = "Clinical Cancer Research",

number = "2",

}

TY - JOUR

T1 - Int7G24A Variant of Transforming Growth Factor-β Receptor Type I is Associated with Invasive Breast Cancer

AU - Chen, Taiping

AU - Jackson, Chad R.

AU - Link, Andrew

AU - Markey, Michael P.

AU - Colligan, Bruce M.

AU - Douglass, Larry E.

AU - Pemberton, Jackson O.

AU - Deddens, James A.

AU - Graff, Jeremy R.

AU - Carter, Julia

PY - 2006/1/15

Y1 - 2006/1/15

N2 - Purpose: The transforming growth factor-β (TGF-β) signaling pathway has been frequently implicated in breast cancer. An intronic variant ( Int7G24A ) of TGF-β receptor type I ( TGFBR1 ) is associated with kidney and bladder cancers in our recent study. We hypothesize that this germline variant may be involved in development and progression of breast cancer. Experimental Design: Case-control studies were designed from archived paraffin-embedded tissue specimens from the same geographic area with a homogenous ethnic population. We analyzed 223 patients (25 with preinvasive tumors and 198 with invasive and metastatic breast cancers) and 153 noncancer controls. The Int7G24A was identified by PCR-RFLP. Another germline deletion ( TGFBR1*6A ) and somatic mutations in the TGFBR1 were also analyzed by PCR and single-strand conformational polymorphism. Results: The Int7G24A allele was evident in 32% of patients with preinvasive neoplasms and 48% of patients with invasive breast cancers compared with 26% controls ( P = 0.00008). In addition, 11 (5.6%) homozygous Int7G24A carriers were found in patients with invasive breast cancers, whereas only 3 (2%) homozygous carriers were found in the control group. The TGFBR1*6A allele was not significantly associated with breast cancer patients and only one somatic mutation was found in 71 breast cancers. Conclusion: These data suggest that the germline Int7G24A variant may represent a risk factor for invasive breast cancer and a marker for breast cancer progression. A separate study with a larger sample size is warranted to validate the association of the Int7G24A with human breast cancer.

AB - Purpose: The transforming growth factor-β (TGF-β) signaling pathway has been frequently implicated in breast cancer. An intronic variant ( Int7G24A ) of TGF-β receptor type I ( TGFBR1 ) is associated with kidney and bladder cancers in our recent study. We hypothesize that this germline variant may be involved in development and progression of breast cancer. Experimental Design: Case-control studies were designed from archived paraffin-embedded tissue specimens from the same geographic area with a homogenous ethnic population. We analyzed 223 patients (25 with preinvasive tumors and 198 with invasive and metastatic breast cancers) and 153 noncancer controls. The Int7G24A was identified by PCR-RFLP. Another germline deletion ( TGFBR1*6A ) and somatic mutations in the TGFBR1 were also analyzed by PCR and single-strand conformational polymorphism. Results: The Int7G24A allele was evident in 32% of patients with preinvasive neoplasms and 48% of patients with invasive breast cancers compared with 26% controls ( P = 0.00008). In addition, 11 (5.6%) homozygous Int7G24A carriers were found in patients with invasive breast cancers, whereas only 3 (2%) homozygous carriers were found in the control group. The TGFBR1*6A allele was not significantly associated with breast cancer patients and only one somatic mutation was found in 71 breast cancers. Conclusion: These data suggest that the germline Int7G24A variant may represent a risk factor for invasive breast cancer and a marker for breast cancer progression. A separate study with a larger sample size is warranted to validate the association of the Int7G24A with human breast cancer.

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U2 - 10.1158/1078-0432.CCR-05-1518

DO - 10.1158/1078-0432.CCR-05-1518

M3 - Article

VL - 12

JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 2

ER -

Int7G24A Variant of Transforming Growth Factor-β Receptor Type I is Associated with Invasive Breast Cancer

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