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Diet and lifestyle factors interact with MAPK genes to influence survival: the Breast Cancer Health Disparities Study

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Abstract

Introduction

MAPK genes are activated by a variety of factors related to growth factors, hormones, and environmental stress.

Methods

We evaluated associations between 13 MAPK genes and survival among 1,187 nonHispanic White and 1,155 Hispanic/Native American (NA) women diagnosed with breast cancer. We assessed the influence of diet, lifestyle, and genetic ancestry on these associations. Percent NA ancestry was determined from 104 Ancestry Informative Markers. Adaptive rank truncation product (ARTP) was used to determine gene and pathway significance.

Results

Associations were predominantly observed among women with lower NA ancestry. Specifically, the mitogen-activated protein kinases (MAPK) pathway was associated with all-cause mortality (P ARTP = 0.02), but not with breast cancer-specific mortality (P ARTP = 0.10). However, MAP2K1 and MAP3K9 were associated with both breast cancer-specific and all-cause mortality. MAPK12 (P ARTP = 0.05) was only associated with breast cancer-specific mortality, and MAP3K1 (P ARTP = 0.02) and MAPK1 (P ARTP = 0.05) were only associated with all-cause mortality. Among women with higher NA ancestry, MAP3K2 was significantly associated with all-cause mortality (P ARTP = 0.04). Several diet and lifestyle factors, including alcohol consumption, caloric intake, dietary folate, and cigarette smoking, significantly modified the associations with MAPK genes and all-cause mortality.

Conclusions

Our study supports an association between MAPK genes and survival after diagnosis with breast cancer, especially among women with low NA ancestry. The interaction between genetic variation in the MAPK pathway with diet and lifestyle factors for all women supports the important role of these factors for breast cancer survivorship.

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Acknowledgments

We would also like to acknowledge the contributions of the following individuals to the study: Sandra Edwards for data harmonization oversight; Jennifer Herrick for data management and data harmonization; Erica Wolff and Michael Hoffman for laboratory support; Carolina Ortega for her assistance with data management for the Mexico Breast Cancer Study, Jocelyn Koo for data management for the San Francisco Bay Area Breast Cancer Study; Dr Tim Byers for his contribution to the 4-Corners Breast Cancer Study; and Dr Josh Galanter for assistance in selection of AIMs markers. The Breast Cancer Health Disparities Study was funded by Grant CA14002 from the National Cancer Institute to Dr Slattery. The San Francisco Bay Area Breast Cancer Study was supported by Grants CA63446 and CA77305 from the National Cancer Institute, Grant DAMD17-96-1-6071 from the US Department of Defense and Grant 7PB-0068 from the California Breast Cancer Research Program. The collection of cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Sect. 103885; the National Cancer Institute’s Surveillance, Epidemiology and End Results Program under contract HHSN261201000036C awarded to the Cancer Prevention Institute of California; and the Centers for Disease Control and Prevention’s National Program of Cancer Registries, under agreement #1U58 DP000807-01 awarded to the Public Health Institute. The 4-Corners Breast Cancer Study was funded by Grants CA078682, CA078762, CA078552, and CA078802 from the National Cancer Institute. The research also was supported by the Utah Cancer Registry, which is funded by contract N01-PC-67000 from the National Cancer Institute, with additional support from the State of Utah Department of Health, the New Mexico Tumor Registry, and the Arizona and Colorado cancer registries, funded by the Centers for Disease Control and Prevention National Program of Cancer Registries and additional state support. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official view of the National Cancer Institute or endorsement by the State of California Department of Public Health, the National Cancer Institute, and the Centers for Disease Control and Prevention or their Contractors and Subcontractors. The Mexico Breast Cancer Study was funded by Consejo Nacional de Ciencia y Tecnología (CONACyT) (SALUD-2002-C01-7462).

Conflict of interest

The authors have no conflict of interest to report.

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Authors and Affiliations

  1. Department of Medicine, University of Utah, 383 Colorow, Salt Lake City, UT, 84108, USA

    Martha L. Slattery, Abbie Lundgreen & Roger K. Wolff

  2. Department of Biology, University of Colorado at Colorado Springs, Colorado Springs, CO, 80918, USA

    Lisa H. Hines

  3. Department of Epidemiology and Population Health, James Graham Brown Cancer Center, School of Public Health and Information Sciences, University of Louisville, Louisville, KY, 40292, USA

    Kathy B. Baumgartner

  4. Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, 90089, USA

    Mariana C. Stern

  5. Cancer Prevention Institute of California, Fremont, CA, 94538, USA

    Esther M. John

  6. Division of Epidemiology, Department of Health Research and Policy and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, 94305, USA

    Esther M. John

Authors
  1. Martha L. Slattery
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  2. Lisa H. Hines
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  3. Abbie Lundgreen
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  4. Kathy B. Baumgartner
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  5. Roger K. Wolff
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  6. Mariana C. Stern
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  7. Esther M. John
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Corresponding author

Correspondence to Martha L. Slattery.

Additional information

Novelty This study evaluates lifestyle and genetic factors that influence breast cancer survival. These factors are evaluated in a large genetically admixed population.

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Slattery, M.L., Hines, L.H., Lundgreen, A. et al. Diet and lifestyle factors interact with MAPK genes to influence survival: the Breast Cancer Health Disparities Study. Cancer Causes Control 25, 1211–1225 (2014). https://doi.org/10.1007/s10552-014-0426-y

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  • DOI: https://doi.org/10.1007/s10552-014-0426-y

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