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Original Article |

Basal Cell Carcinoma:  Stressful Life Events and the Tumor Environment

Christopher P. Fagundes, PhD; Ronald Glaser, PhD; Sheri L. Johnson, PhD; Rebecca R. Andridge, PhD; Eric V. Yang, PhD; Michael P. Di Gregorio, MS; Min Chen, MS; David R. Lambert, MD; Scott D. Jewell, MD; Mark A. Bechtel, MD; Dean W. Hearne, MD; Joel B. Herron, MD; Janice K. Kiecolt-Glaser, PhD
Arch Gen Psychiatry. 2012;69(6):618-626. doi:10.1001/archgenpsychiatry.2011.1535.
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Context  Child emotional maltreatment can result in lasting immune dysregulation that may be heightened in the context of more recent life stress. Basal cell carcinoma (BCC) is the most common skin cancer, and the immune system plays a prominent role in tumor appearance and progression.

Objective  To address associations among recent severe life events, childhood parental emotional maltreatment, depression, and messenger RNA (mRNA) coding for immune markers associated with BCC tumor progression and regression.

Design  We collected information about early parent-child experiences, severe life events in the past year as assessed by the Life Events and Difficulties Schedule, depression, and mRNA for immune markers associated with BCC tumor progression and regression from patients with BCC tumors.

Setting  University medical center.

Participants  Ninety-one patients with BCC (ages, 23-92 years) who had a previous BCC tumor.

Main Outcome Measures  The expression of 4 BCC tumor mRNA markers (CD25, CD3ϵ, intercellular adhesion molecule 1, and CD68) that have been linked to BCC tumor progression and regression were assessed in BCC tumor biopsy specimens.

Results  Both maternal and paternal emotional maltreatment interacted with the occurrence of severe life events to predict the local immune response to the tumor (adjusted P = .009 and P = .03, respectively). Among BCC patients who had experienced a severe life event within the past year, those who were emotionally maltreated by their mothers (P = .007) or fathers (P = .02) as children had a poorer immune response to the BCC tumor. Emotional maltreatment was unrelated to BCC immune responses among those who did not experience a severe life event. Depressive symptoms were not associated with the local tumor immune response.

Conclusions  Troubled early parent-child relationships, in combination with a severe life event in the past year, predicted immune responses to a BCC tumor. The immunoreactivity observed in BCCs and the surrounding stroma reflects an anti–tumor-specific immune response that can be altered by stress.

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Figures

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Grahic Jump Location

Figure. Interaction plot illustrating the association among maternal emotional maltreatment, severe life events, and composite messenger RNA (mRNA) z score from the adjusted model in Table 2. Values of all other variables in the model are set to their sample means.

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