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01-10-2019 | Cervical Cancer | Original Paper

Inherited alterations of TGF beta signaling components in Appalachian cervical cancers

Authors: Thomas J. Knobloch, Juan Peng, Erinn M. Hade, David E. Cohn, Mack T. Ruffin IV, Michael A. Schiano, Byron C. Calhoun, William C. McBee Jr., 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. DeGraffinreid, Electra D. Paskett, Christopher M. Weghorst

Published in: Cancer Causes & Control | Issue 10/2019

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.

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Title: Inherited alterations of TGF beta signaling components in Appalachian cervical cancers
Authors: Thomas J. Knobloch
Juan Peng
Erinn M. Hade
David E. Cohn
Mack T. Ruffin IV
Michael A. Schiano
Byron C. Calhoun
William C. McBee Jr.
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. DeGraffinreid
Electra D. Paskett
Christopher M. Weghorst
Publication date: 01-10-2019
Publisher: Springer International Publishing
Keywords: Cervical Cancer
Cervical Cancer
Published in: Cancer Causes & Control / Issue 10/2019
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI: https://doi.org/10.1007/s10552-019-01221-y

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