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Inherited alterations of TGF beta signaling components in Appalachian cervical cancers.
- Source :
-
Cancer causes & control : CCC [Cancer Causes Control] 2019 Oct; Vol. 30 (10), pp. 1087-1100. Date of Electronic Publication: 2019 Aug 21. - Publication Year :
- 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.<br />Methods: Appalachian women's survey data and blood samples from the Community Awareness, Resources, and Education (CARE) CARE I and CARE II studies (nā=ā163 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 Ļ <superscript>2</superscript> tests. Multivariable logistic regression was used to evaluate interaction effects between genomic variance and demographic, behavioral, and environmental characteristics.<br />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.<br />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.
- Subjects :
- Adult
Aged
Alleles
Female
Gene-Environment Interaction
Humans
Kentucky epidemiology
Logistic Models
Middle Aged
NAD(P)H Dehydrogenase (Quinone) genetics
Ohio epidemiology
Receptor, Transforming Growth Factor-beta Type I genetics
Risk Factors
Signal Transduction
Uterine Cervical Neoplasms epidemiology
West Virginia epidemiology
Young Adult
Transforming Growth Factor beta1 genetics
Uterine Cervical Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1573-7225
- Volume :
- 30
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Cancer causes & control : CCC
- Publication Type :
- Academic Journal
- Accession number :
- 31435875
- Full Text :
- https://doi.org/10.1007/s10552-019-01221-y