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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. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: This article describes recruitment of a subpopulation of women in a rural area, extending an existing method of a 2‐phase address‐based sampling protocol to include a mixed‐mode approach. Methods: Phase 1 included a household enumeration questionnaire mailed to randomly selected households (n = 1,950) in 3 Ohio Appalachian counties to identify members of the eligible subgroup. The second phase of recruitment involved contacting 1 randomly selected eligible woman enumerated by each household, based on return of the questionnaire. These women (n = 599) were invited by field interviewers to participate in a one‐time in‐person health survey. Findings: Of the women invited to participate, a total of 408 completed the interview. Based on American Association for Public Opinion Research Response Rate 1 calculations, the response rates were 44.4% and 70.3% for phases 1 and 2, respectively. Response rates in this study were encouraging, especially for the second phase in‐person interview. Conclusion: We discuss implications for future research using a mixed‐mode approach in this subpopulation. [ABSTRACT FROM AUTHOR]

Introduction: Electronic cigarette (e-cigarette) use among adolescents is associated with increased risk of subsequent cigarette smoking initiation in observational research. However, the existing research was not designed to answer causal questions about whether adolescent e-cigarette users would have initiated cigarette smoking if they had never used e-cigarettes. The current study used a causal inference framework to identify whether male adolescent e-cigarette users were at increased risk of initiating cigarette smoking and smokeless tobacco (SLT) use, compared to similar boys who had never used e-cigarettes.Methods: Boys from urban and Appalachian Ohio (N = 1220; ages 11-16 years at enrollment) reported use of e-cigarettes, cigarettes, and SLT at baseline and every six months for two years. A propensity score matching design was implemented, matching one e-cigarette user to two similar e-cigarette non-users. This analysis was completed in 25 multiple imputed datasets to account for missing data. Risk ratios (RRs) comparing risk of initiating cigarettes and SLT for e-cigarette users and nonusers were estimated.Results: Compared to non-users, e-cigarette users were more than twice as likely to later initiate both cigarette smoking (RR = 2.71; 95% CI: 1.89, 3.87) and SLT (RR = 2.42; 95% CI: 1.73, 3.38). They were also more likely to become current (i.e., past 30-day) cigarette smokers (RR = 2.20; 95% CI: 1.33, 3.64) and SLT users (RR = 1.64; 95% CI: 1.01, 2.64).Conclusions: Adolescent boys who used e-cigarettes had increased risk of later initiating traditional tobacco products when compared to similar boys who had never used e-cigarettes. [ABSTRACT FROM AUTHOR]

The Appalachian region experiences higher incidence and mortality due to cervical cancer compared with other regions of the United States. The goal of the Ohio State University Center for Population Health and Health Disparities (CPHHD), called the Community Awareness Resources and Education (CARE) project, was to understand reasons for this disparity. The first wave (2003-2008) of funding included three projects focusing on the known risk factors for cervical cancer, lack of screening, smoking, and infection with human papillomavirus (HPV). On the basis of the results of these projects, the second wave (2011-2017) included four projects, designed to address a multi-level model of factors contributing to cervical disparities in Appalachia. The results of these projects were then used to refine a multi-level model that explains cervical cancer disparities in Appalachia. Future funded projects will take these multi-level explanations for cervical disparities and focus on implementation science strategies to reduce the burden of cervical cancer morbidity and mortality in Appalachia. See all articles in this Special Collection Honoring Paul F. Engstrom, MD, Champion of Cancer Prevention ., (©2020 American Association for Cancer Research.)