Biological Aging Marker p16<sup>INK4a</sup> in T Cells and Breast Cancer Risk
Prior research has demonstrated that altered telomere length, a well-known marker for biological aging, is associated with various types of human cancer. However, whether such association extends to additional hallmarks of biological aging, including cellular senescence, has not been determined yet....
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-10-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/12/11/3122 |
| _version_ | 1797549919754518528 |
|---|---|
| author | Jie Shen Renduo Song Bernard F. Fuemmeler Kandace P. McGuire Wong-Ho Chow Hua Zhao |
| author_facet | Jie Shen Renduo Song Bernard F. Fuemmeler Kandace P. McGuire Wong-Ho Chow Hua Zhao |
| author_sort | Jie Shen |
| collection | DOAJ |
| description | Prior research has demonstrated that altered telomere length, a well-known marker for biological aging, is associated with various types of human cancer. However, whether such association extends to additional hallmarks of biological aging, including cellular senescence, has not been determined yet. In this two-stage study, we assessed the association between <em>p16<sup>INK4a</sup></em> mRNA expression in T cells, a marker of cellular senescence, and breast cancer risk. The discovery stage included 352 breast cancer patients and 324 healthy controls. <em>p16<sup>INK4a</sup></em> mRNA expression was significantly higher in individuals who were older, Black, and had family history of cancer than their counterparts in both cases and controls. <em>p16<sup>INK4a</sup></em> mRNA expression also differed by marital status, annual income, and smoking status in cases. In the discovery stage, we found that increased <em>p16<sup>INK4a</sup></em> mRNA expression was associated with 1.40-fold increased risk of breast cancer (OR = 1.40; 95%CI: 1.21, 1.68; <em>p </em>< 0.001). A marginally significant association was further observed in the validation stage with 47 cases and 48 controls using pre-diagnostic samples (OR = 1.28; 95%CI: 0.98, 2.97; <em>p </em>= 0.053). In addition, we found that <em>p16<sup>INK4a</sup></em> mRNA expression was higher in tumors with selected aggressive characteristics (e.g., poorly differentiated and large tumors) than their counterparts. In summary, our results demonstrate that higher <em>p16<sup>INK4a</sup></em> mRNA expression in T cells is a risk factor for breast cancer and further support the role of biological aging in the etiology of breast cancer development. Novelty and Impact Statements<strong>:</strong> The results from this study provide evidence that cellular senescence, a process of biological aging, plays a role in breast cancer etiology. In addition, our results also support that social demographics may modify cellular senescence and biological aging. |
| first_indexed | 2024-03-10T15:21:15Z |
| format | Article |
| id | doaj.art-f625acbc38ca48d383db61d744c547c5 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T15:21:15Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-f625acbc38ca48d383db61d744c547c52023-11-20T18:30:11ZengMDPI AGCancers2072-66942020-10-011211312210.3390/cancers12113122Biological Aging Marker p16<sup>INK4a</sup> in T Cells and Breast Cancer RiskJie Shen0Renduo Song1Bernard F. Fuemmeler2Kandace P. McGuire3Wong-Ho Chow4Hua Zhao5Departments of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartments of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USAHealth Behavior and Policy, School of Medicine, Virginia Commonwealth University, Richmond, VA 23284, USADepartment of Surgery, School of Medicine, Virginia Commonwealth University, Richmond, VA 23284, USADepartments of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartments of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USAPrior research has demonstrated that altered telomere length, a well-known marker for biological aging, is associated with various types of human cancer. However, whether such association extends to additional hallmarks of biological aging, including cellular senescence, has not been determined yet. In this two-stage study, we assessed the association between <em>p16<sup>INK4a</sup></em> mRNA expression in T cells, a marker of cellular senescence, and breast cancer risk. The discovery stage included 352 breast cancer patients and 324 healthy controls. <em>p16<sup>INK4a</sup></em> mRNA expression was significantly higher in individuals who were older, Black, and had family history of cancer than their counterparts in both cases and controls. <em>p16<sup>INK4a</sup></em> mRNA expression also differed by marital status, annual income, and smoking status in cases. In the discovery stage, we found that increased <em>p16<sup>INK4a</sup></em> mRNA expression was associated with 1.40-fold increased risk of breast cancer (OR = 1.40; 95%CI: 1.21, 1.68; <em>p </em>< 0.001). A marginally significant association was further observed in the validation stage with 47 cases and 48 controls using pre-diagnostic samples (OR = 1.28; 95%CI: 0.98, 2.97; <em>p </em>= 0.053). In addition, we found that <em>p16<sup>INK4a</sup></em> mRNA expression was higher in tumors with selected aggressive characteristics (e.g., poorly differentiated and large tumors) than their counterparts. In summary, our results demonstrate that higher <em>p16<sup>INK4a</sup></em> mRNA expression in T cells is a risk factor for breast cancer and further support the role of biological aging in the etiology of breast cancer development. Novelty and Impact Statements<strong>:</strong> The results from this study provide evidence that cellular senescence, a process of biological aging, plays a role in breast cancer etiology. In addition, our results also support that social demographics may modify cellular senescence and biological aging.https://www.mdpi.com/2072-6694/12/11/3122p16<sup>INK4a</sup>breast cancerstressbiological aging |
| spellingShingle | Jie Shen Renduo Song Bernard F. Fuemmeler Kandace P. McGuire Wong-Ho Chow Hua Zhao Biological Aging Marker p16<sup>INK4a</sup> in T Cells and Breast Cancer Risk Cancers p16<sup>INK4a</sup> breast cancer stress biological aging |
| title | Biological Aging Marker p16<sup>INK4a</sup> in T Cells and Breast Cancer Risk |
| title_full | Biological Aging Marker p16<sup>INK4a</sup> in T Cells and Breast Cancer Risk |
| title_fullStr | Biological Aging Marker p16<sup>INK4a</sup> in T Cells and Breast Cancer Risk |
| title_full_unstemmed | Biological Aging Marker p16<sup>INK4a</sup> in T Cells and Breast Cancer Risk |
| title_short | Biological Aging Marker p16<sup>INK4a</sup> in T Cells and Breast Cancer Risk |
| title_sort | biological aging marker p16 sup ink4a sup in t cells and breast cancer risk |
| topic | p16<sup>INK4a</sup> breast cancer stress biological aging |
| url | https://www.mdpi.com/2072-6694/12/11/3122 |
| work_keys_str_mv | AT jieshen biologicalagingmarkerp16supink4asupintcellsandbreastcancerrisk AT renduosong biologicalagingmarkerp16supink4asupintcellsandbreastcancerrisk AT bernardffuemmeler biologicalagingmarkerp16supink4asupintcellsandbreastcancerrisk AT kandacepmcguire biologicalagingmarkerp16supink4asupintcellsandbreastcancerrisk AT wonghochow biologicalagingmarkerp16supink4asupintcellsandbreastcancerrisk AT huazhao biologicalagingmarkerp16supink4asupintcellsandbreastcancerrisk |