Inherited alterations of TGF beta signaling components in Appalachian cervical cancers

Thomas J. Knobloch, Juan Peng, Erinn M. Hade, David E. Cohn, Mack Ruffin, Michael A. Schiano, Byron C. Calhoun, William C. McBee, Jamie L. Lesnock, Holly H. Gallion, Jondavid Pollock, Bo Lu, Steve Oghumu, Zhaoxia Zhang, Marta T. Sears, Blessing E. Ogbemudia, Joseph T. Perrault, Logan C. Weghorst, Erin Strawser, Cecilia R. DeGraffinreidElectra D. Paskett, Christopher M. Weghorst

Research output: Contribution to journalArticle

Abstract

Purpose: This study examined targeted genomic variants of transforming growth factor beta (TGFB) signaling in Appalachian women. Appalachian women with cervical cancer were compared to healthy Appalachian counterparts to determine whether these polymorphic alleles were over-represented within this high-risk cancer population, and whether lifestyle or environmental factors modified the aggregate genetic risk in these Appalachian women. Methods: Appalachian women’s survey data and blood samples from the Community Awareness, Resources, and Education (CARE) CARE I and CARE II studies (n = 163 invasive cervical cancer cases, 842 controls) were used to assess gene–environment interactions and cancer risk. Polymorphic allele frequencies and socio-behavioral demographic measurements were compared using t tests and χ2 tests. Multivariable logistic regression was used to evaluate interaction effects between genomic variance and demographic, behavioral, and environmental characteristics. Results: Several alleles demonstrated significant interaction with smoking (TP53 rs1042522, TGFB1 rs1800469), alcohol consumption (NQO1 rs1800566), and sexual intercourse before the age of 18 (TGFBR1 rs11466445, TGFBR1 rs7034462, TGFBR1 rs11568785). Interestingly, we noted a significant interaction between “Appalachian self-identity” variables and NQO1 rs1800566. Multivariable logistic regression of cancer status in an over-dominant TGFB1 rs1800469/TGFBR1 rs11568785 model demonstrated a 3.03-fold reduction in cervical cancer odds. Similar decreased odds (2.78-fold) were observed in an over-dominant TGFB1 rs1800469/TGFBR1 rs7034462 model in subjects who had no sexual intercourse before age 18. Conclusions: This study reports novel associations between common low-penetrance alleles in the TGFB signaling cascade and modified risk of cervical cancer in Appalachian women. Furthermore, our unexpected findings associating Appalachian identity and NQO1 rs1800566 suggests that the complex environmental exposures that contribute to Appalachian self-identity in Appalachian cervical cancer patients represent an emerging avenue of scientific exploration.

Original languageEnglish (US)
Pages (from-to)1087-1100
Number of pages14
JournalCancer Causes and Control
Volume30
Issue number10
DOIs
StatePublished - Oct 1 2019

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Uterine Cervical Neoplasms
Transforming Growth Factor beta
Coitus
Alleles
Logistic Models
Demography
Neoplasms
Penetrance
Environmental Exposure
Gene Frequency
Alcohol Drinking
Life Style
Smoking
Education
Population

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Knobloch, T. J., Peng, J., Hade, E. M., Cohn, D. E., Ruffin, M., Schiano, M. A., ... Weghorst, C. M. (2019). Inherited alterations of TGF beta signaling components in Appalachian cervical cancers. Cancer Causes and Control, 30(10), 1087-1100. https://doi.org/10.1007/s10552-019-01221-y
Knobloch, Thomas J. ; Peng, Juan ; Hade, Erinn M. ; Cohn, David E. ; Ruffin, Mack ; Schiano, Michael A. ; Calhoun, Byron C. ; McBee, William C. ; Lesnock, Jamie L. ; Gallion, Holly H. ; Pollock, Jondavid ; Lu, Bo ; Oghumu, Steve ; Zhang, Zhaoxia ; Sears, Marta T. ; Ogbemudia, Blessing E. ; Perrault, Joseph T. ; Weghorst, Logan C. ; Strawser, Erin ; DeGraffinreid, Cecilia R. ; Paskett, Electra D. ; Weghorst, Christopher M. / Inherited alterations of TGF beta signaling components in Appalachian cervical cancers. In: Cancer Causes and Control. 2019 ; Vol. 30, No. 10. pp. 1087-1100.
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abstract = "Purpose: This study examined targeted genomic variants of transforming growth factor beta (TGFB) signaling in Appalachian women. Appalachian women with cervical cancer were compared to healthy Appalachian counterparts to determine whether these polymorphic alleles were over-represented within this high-risk cancer population, and whether lifestyle or environmental factors modified the aggregate genetic risk in these Appalachian women. Methods: Appalachian women’s survey data and blood samples from the Community Awareness, Resources, and Education (CARE) CARE I and CARE II studies (n = 163 invasive cervical cancer cases, 842 controls) were used to assess gene–environment interactions and cancer risk. Polymorphic allele frequencies and socio-behavioral demographic measurements were compared using t tests and χ2 tests. Multivariable logistic regression was used to evaluate interaction effects between genomic variance and demographic, behavioral, and environmental characteristics. Results: Several alleles demonstrated significant interaction with smoking (TP53 rs1042522, TGFB1 rs1800469), alcohol consumption (NQO1 rs1800566), and sexual intercourse before the age of 18 (TGFBR1 rs11466445, TGFBR1 rs7034462, TGFBR1 rs11568785). Interestingly, we noted a significant interaction between “Appalachian self-identity” variables and NQO1 rs1800566. Multivariable logistic regression of cancer status in an over-dominant TGFB1 rs1800469/TGFBR1 rs11568785 model demonstrated a 3.03-fold reduction in cervical cancer odds. Similar decreased odds (2.78-fold) were observed in an over-dominant TGFB1 rs1800469/TGFBR1 rs7034462 model in subjects who had no sexual intercourse before age 18. Conclusions: This study reports novel associations between common low-penetrance alleles in the TGFB signaling cascade and modified risk of cervical cancer in Appalachian women. Furthermore, our unexpected findings associating Appalachian identity and NQO1 rs1800566 suggests that the complex environmental exposures that contribute to Appalachian self-identity in Appalachian cervical cancer patients represent an emerging avenue of scientific exploration.",
author = "Knobloch, {Thomas J.} and Juan Peng and Hade, {Erinn M.} and Cohn, {David E.} and Mack Ruffin and Schiano, {Michael A.} and Calhoun, {Byron C.} and McBee, {William C.} and Lesnock, {Jamie L.} and Gallion, {Holly H.} and Jondavid Pollock and Bo Lu and Steve Oghumu and Zhaoxia Zhang and Sears, {Marta T.} and Ogbemudia, {Blessing E.} and Perrault, {Joseph T.} and Weghorst, {Logan C.} and Erin Strawser and DeGraffinreid, {Cecilia R.} and Paskett, {Electra D.} and Weghorst, {Christopher M.}",
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Knobloch, TJ, Peng, J, Hade, EM, Cohn, DE, Ruffin, M, Schiano, MA, Calhoun, BC, McBee, WC, Lesnock, JL, Gallion, HH, Pollock, J, Lu, B, Oghumu, S, Zhang, Z, Sears, MT, Ogbemudia, BE, Perrault, JT, Weghorst, LC, Strawser, E, DeGraffinreid, CR, Paskett, ED & Weghorst, CM 2019, 'Inherited alterations of TGF beta signaling components in Appalachian cervical cancers', Cancer Causes and Control, vol. 30, no. 10, pp. 1087-1100. https://doi.org/10.1007/s10552-019-01221-y

Inherited alterations of TGF beta signaling components in Appalachian cervical cancers. / Knobloch, Thomas J.; Peng, Juan; Hade, Erinn M.; Cohn, David E.; Ruffin, Mack; Schiano, Michael A.; Calhoun, Byron C.; McBee, William C.; Lesnock, Jamie L.; Gallion, Holly H.; Pollock, Jondavid; Lu, Bo; Oghumu, Steve; Zhang, Zhaoxia; Sears, Marta T.; Ogbemudia, Blessing E.; Perrault, Joseph T.; Weghorst, Logan C.; Strawser, Erin; DeGraffinreid, Cecilia R.; Paskett, Electra D.; Weghorst, Christopher M.

In: Cancer Causes and Control, Vol. 30, No. 10, 01.10.2019, p. 1087-1100.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Inherited alterations of TGF beta signaling components in Appalachian cervical cancers

AU - Knobloch, Thomas J.

AU - Peng, Juan

AU - Hade, Erinn M.

AU - Cohn, David E.

AU - Ruffin, Mack

AU - Schiano, Michael A.

AU - Calhoun, Byron C.

AU - McBee, William C.

AU - Lesnock, Jamie L.

AU - Gallion, Holly H.

AU - Pollock, Jondavid

AU - Lu, Bo

AU - Oghumu, Steve

AU - Zhang, Zhaoxia

AU - Sears, Marta T.

AU - Ogbemudia, Blessing E.

AU - Perrault, Joseph T.

AU - Weghorst, Logan C.

AU - Strawser, Erin

AU - DeGraffinreid, Cecilia R.

AU - Paskett, Electra D.

AU - Weghorst, Christopher M.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Purpose: This study examined targeted genomic variants of transforming growth factor beta (TGFB) signaling in Appalachian women. Appalachian women with cervical cancer were compared to healthy Appalachian counterparts to determine whether these polymorphic alleles were over-represented within this high-risk cancer population, and whether lifestyle or environmental factors modified the aggregate genetic risk in these Appalachian women. Methods: Appalachian women’s survey data and blood samples from the Community Awareness, Resources, and Education (CARE) CARE I and CARE II studies (n = 163 invasive cervical cancer cases, 842 controls) were used to assess gene–environment interactions and cancer risk. Polymorphic allele frequencies and socio-behavioral demographic measurements were compared using t tests and χ2 tests. Multivariable logistic regression was used to evaluate interaction effects between genomic variance and demographic, behavioral, and environmental characteristics. Results: Several alleles demonstrated significant interaction with smoking (TP53 rs1042522, TGFB1 rs1800469), alcohol consumption (NQO1 rs1800566), and sexual intercourse before the age of 18 (TGFBR1 rs11466445, TGFBR1 rs7034462, TGFBR1 rs11568785). Interestingly, we noted a significant interaction between “Appalachian self-identity” variables and NQO1 rs1800566. Multivariable logistic regression of cancer status in an over-dominant TGFB1 rs1800469/TGFBR1 rs11568785 model demonstrated a 3.03-fold reduction in cervical cancer odds. Similar decreased odds (2.78-fold) were observed in an over-dominant TGFB1 rs1800469/TGFBR1 rs7034462 model in subjects who had no sexual intercourse before age 18. Conclusions: This study reports novel associations between common low-penetrance alleles in the TGFB signaling cascade and modified risk of cervical cancer in Appalachian women. Furthermore, our unexpected findings associating Appalachian identity and NQO1 rs1800566 suggests that the complex environmental exposures that contribute to Appalachian self-identity in Appalachian cervical cancer patients represent an emerging avenue of scientific exploration.

AB - Purpose: This study examined targeted genomic variants of transforming growth factor beta (TGFB) signaling in Appalachian women. Appalachian women with cervical cancer were compared to healthy Appalachian counterparts to determine whether these polymorphic alleles were over-represented within this high-risk cancer population, and whether lifestyle or environmental factors modified the aggregate genetic risk in these Appalachian women. Methods: Appalachian women’s survey data and blood samples from the Community Awareness, Resources, and Education (CARE) CARE I and CARE II studies (n = 163 invasive cervical cancer cases, 842 controls) were used to assess gene–environment interactions and cancer risk. Polymorphic allele frequencies and socio-behavioral demographic measurements were compared using t tests and χ2 tests. Multivariable logistic regression was used to evaluate interaction effects between genomic variance and demographic, behavioral, and environmental characteristics. Results: Several alleles demonstrated significant interaction with smoking (TP53 rs1042522, TGFB1 rs1800469), alcohol consumption (NQO1 rs1800566), and sexual intercourse before the age of 18 (TGFBR1 rs11466445, TGFBR1 rs7034462, TGFBR1 rs11568785). Interestingly, we noted a significant interaction between “Appalachian self-identity” variables and NQO1 rs1800566. Multivariable logistic regression of cancer status in an over-dominant TGFB1 rs1800469/TGFBR1 rs11568785 model demonstrated a 3.03-fold reduction in cervical cancer odds. Similar decreased odds (2.78-fold) were observed in an over-dominant TGFB1 rs1800469/TGFBR1 rs7034462 model in subjects who had no sexual intercourse before age 18. Conclusions: This study reports novel associations between common low-penetrance alleles in the TGFB signaling cascade and modified risk of cervical cancer in Appalachian women. Furthermore, our unexpected findings associating Appalachian identity and NQO1 rs1800566 suggests that the complex environmental exposures that contribute to Appalachian self-identity in Appalachian cervical cancer patients represent an emerging avenue of scientific exploration.

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