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Global DNA Methylation, Measured by the Luminometric Methylation Assay (LUMA), Associates with Postmenopausal Breast Cancer in Non-Obese and Physically Active Women

Introduction: Little is known about how modifiable lifestyle factors interact with the epigenome to influence disease. Body mass index (BMI, weight kg/height m2) and physical activity are associated with postmenopausal breast cancer, but the mechanisms are not well-understood. We hypothesized that B...

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Autores principales: McCullough, Lauren E., Chen, Jia, White, Alexandra J., Xu, Xinran, Cho, Yoon Hee, Bradshaw, Patrick T., Eng, Sybil M., Teitelbaum, Susan L., Terry, Mary Beth, Garbowski, Gail, Neugut, Alfred I., Hibshoosh, Hanina, Santella, Regina M., Gammon, Marilie D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439941/
https://www.ncbi.nlm.nih.gov/pubmed/26000047
http://dx.doi.org/10.7150/jca.11359
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author McCullough, Lauren E.
Chen, Jia
White, Alexandra J.
Xu, Xinran
Cho, Yoon Hee
Bradshaw, Patrick T.
Eng, Sybil M.
Teitelbaum, Susan L.
Terry, Mary Beth
Garbowski, Gail
Neugut, Alfred I.
Hibshoosh, Hanina
Santella, Regina M.
Gammon, Marilie D.
author_facet McCullough, Lauren E.
Chen, Jia
White, Alexandra J.
Xu, Xinran
Cho, Yoon Hee
Bradshaw, Patrick T.
Eng, Sybil M.
Teitelbaum, Susan L.
Terry, Mary Beth
Garbowski, Gail
Neugut, Alfred I.
Hibshoosh, Hanina
Santella, Regina M.
Gammon, Marilie D.
author_sort McCullough, Lauren E.
collection PubMed
description Introduction: Little is known about how modifiable lifestyle factors interact with the epigenome to influence disease. Body mass index (BMI, weight kg/height m2) and physical activity are associated with postmenopausal breast cancer, but the mechanisms are not well-understood. We hypothesized that BMI or physical activity may modify the association between markers of global DNA methylation and postmenopausal breast cancer risk. Methods: Resources from a population-based case-control study (~1300 postmenopausal women) were used to construct logistic regression models. We explored whether the association between breast cancer and global methylation, assessed using the luminometric methylation assay (LUMA) and long interspersed elements-1 (LINE-1) methylation in white blood cell DNA, was modified by BMI or recreational physical activity (RPA). Results: The LUMA-breast cancer association was modified by BMI (multiplicative p=0.03) and RPA (p=0.004). Non-obese women in the highest quartile of LUMA experienced a greater than two-fold increased risk of postmenopausal breast cancer (BMI<25kg/m2: OR=2.16; 95% CI=1.35, 3.57 and BMI 25-29.9kg/m2: OR=2.96; 95% CI=1.69, 5.19) compared to women in the lowest LUMA quartile. Similar increases in the LUMA-breast cancer association were observed among women who were physically active (moderate RPA: OR=2.62; 95% CI=1.44, 4.75 and high RPA: OR=2.62; 95% CI=1.53, 4.49). Estimates among obese and inactive women were less pronounced and imprecise. Although we observed statistical interactions (p<0.05) between BMI and RPA with LINE-1, we were unable to discern any clear associations with breast cancer. Conclusions: The association between LUMA and postmenopausal breast cancer risk may be modified by postmenopausal body size and physical activity.
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spelling pubmed-44399412015-05-21 Global DNA Methylation, Measured by the Luminometric Methylation Assay (LUMA), Associates with Postmenopausal Breast Cancer in Non-Obese and Physically Active Women McCullough, Lauren E. Chen, Jia White, Alexandra J. Xu, Xinran Cho, Yoon Hee Bradshaw, Patrick T. Eng, Sybil M. Teitelbaum, Susan L. Terry, Mary Beth Garbowski, Gail Neugut, Alfred I. Hibshoosh, Hanina Santella, Regina M. Gammon, Marilie D. J Cancer Research Paper Introduction: Little is known about how modifiable lifestyle factors interact with the epigenome to influence disease. Body mass index (BMI, weight kg/height m2) and physical activity are associated with postmenopausal breast cancer, but the mechanisms are not well-understood. We hypothesized that BMI or physical activity may modify the association between markers of global DNA methylation and postmenopausal breast cancer risk. Methods: Resources from a population-based case-control study (~1300 postmenopausal women) were used to construct logistic regression models. We explored whether the association between breast cancer and global methylation, assessed using the luminometric methylation assay (LUMA) and long interspersed elements-1 (LINE-1) methylation in white blood cell DNA, was modified by BMI or recreational physical activity (RPA). Results: The LUMA-breast cancer association was modified by BMI (multiplicative p=0.03) and RPA (p=0.004). Non-obese women in the highest quartile of LUMA experienced a greater than two-fold increased risk of postmenopausal breast cancer (BMI<25kg/m2: OR=2.16; 95% CI=1.35, 3.57 and BMI 25-29.9kg/m2: OR=2.96; 95% CI=1.69, 5.19) compared to women in the lowest LUMA quartile. Similar increases in the LUMA-breast cancer association were observed among women who were physically active (moderate RPA: OR=2.62; 95% CI=1.44, 4.75 and high RPA: OR=2.62; 95% CI=1.53, 4.49). Estimates among obese and inactive women were less pronounced and imprecise. Although we observed statistical interactions (p<0.05) between BMI and RPA with LINE-1, we were unable to discern any clear associations with breast cancer. Conclusions: The association between LUMA and postmenopausal breast cancer risk may be modified by postmenopausal body size and physical activity. Ivyspring International Publisher 2015-05-01 /pmc/articles/PMC4439941/ /pubmed/26000047 http://dx.doi.org/10.7150/jca.11359 Text en © 2015 Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions.
spellingShingle Research Paper
McCullough, Lauren E.
Chen, Jia
White, Alexandra J.
Xu, Xinran
Cho, Yoon Hee
Bradshaw, Patrick T.
Eng, Sybil M.
Teitelbaum, Susan L.
Terry, Mary Beth
Garbowski, Gail
Neugut, Alfred I.
Hibshoosh, Hanina
Santella, Regina M.
Gammon, Marilie D.
Global DNA Methylation, Measured by the Luminometric Methylation Assay (LUMA), Associates with Postmenopausal Breast Cancer in Non-Obese and Physically Active Women
title Global DNA Methylation, Measured by the Luminometric Methylation Assay (LUMA), Associates with Postmenopausal Breast Cancer in Non-Obese and Physically Active Women
title_full Global DNA Methylation, Measured by the Luminometric Methylation Assay (LUMA), Associates with Postmenopausal Breast Cancer in Non-Obese and Physically Active Women
title_fullStr Global DNA Methylation, Measured by the Luminometric Methylation Assay (LUMA), Associates with Postmenopausal Breast Cancer in Non-Obese and Physically Active Women
title_full_unstemmed Global DNA Methylation, Measured by the Luminometric Methylation Assay (LUMA), Associates with Postmenopausal Breast Cancer in Non-Obese and Physically Active Women
title_short Global DNA Methylation, Measured by the Luminometric Methylation Assay (LUMA), Associates with Postmenopausal Breast Cancer in Non-Obese and Physically Active Women
title_sort global dna methylation, measured by the luminometric methylation assay (luma), associates with postmenopausal breast cancer in non-obese and physically active women
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439941/
https://www.ncbi.nlm.nih.gov/pubmed/26000047
http://dx.doi.org/10.7150/jca.11359
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