| 1. |
- Berntsson, Jonna, et al.
(författare)
-
Pre-diagnostic anthropometry, sex, and risk of colorectal cancer according to tumor immune cell composition
- 2019
-
Ingår i: OncoImmunology. - 2162-4011. ; 8:12
-
Tidskriftsartikel (refereegranskat)abstract
- Obesity is a well-established risk factor for colorectal cancer (CRC), but the association with the tumor microenvironment has been sparsely described. Herein, we examined the relationship between pre-diagnostic anthropometry and CRC risk according to tumor immune cell composition, with particular reference to potential sex differences. The density of different immune cell subsets was assessed by immunohistochemistry in tissue microarrays with tumors from 584 incident CRC cases in a prospective, population-based cohort (n = 28098). Multivariable Cox regression models, adjusted for age, smoking, alcohol intake, and educational level, were applied to calculate risk of immune marker-defined CRC in relation to quartiles of pre-diagnostic height, weight, body mass index (BMI), waist and hip circumferences, waist-hip ratio (WHR), and body fat percentage (BFP). Obesity was all over significantly associated with risk of CRC with low density of FoxP3+ T cells and low programmed cell-death protein 1 (PD-L1) expression on tumor cells, but with high density of CD8+ T cells and CD20+ B cells. In women, obesity was significantly associated with risk of PD-L1 high tumors (p= 0.009 for weight, p= 0.039 for BMI). Contrastingly, in men, obesity defined by all anthropometric factors was significantly associated with PD-L1 low tumors (p= 0.005 for weight, p = 0.002 for BMI, p<0.001 for waist, p= 0.011 for hip, p<0.001 for WHR, and p= 0.004 for BFP). In summary, obesity appears to influence the immune landscape of CRC, possibly in a sex-dependent manner. Thus, anthropometry and sex may be important factors to take into account when assessing the prognostic or predictive value of relevant complementary immune biomarkers.
|
|
| 2. |
- Berntsson, Jonna
(författare)
-
The immune microenvironment of colorectal cancer - Relationship with survival, sidedness, and pre-diagnostic anthropometry
- 2019
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Colorectal cancer (CRC) is the third most common cancer worldwide. Increasing evidence suggests that CRC should be considered a heterogeneous disease, with multiple differences between proximal and distal tumours. The immune system may, depending on the context, promote or inhibit tumour growth, and different immune cell subsets have been found to be associated with impaired or improved prognosis in CRC. The major aim of this thesis was to investigate the prognostic impact of different immune cell signatures in CRC, with particular reference to primary tumour location, and, furthermore, to perform a characterization of immune cell signatures in relation to anthropometric factors.The study cohort for Papers I-III consists of all 626 cases of CRC in the prospective, population-based cohort Malmö Diet and Cancer Study (MDCS) from 1991 up until December 31, 2008, of which tumours from 557 cases were available for tissue microarray construction, including 201 (36.2%) right-sided and 145 (26.1%) left-sided colon cancers, and 209 (37.7%) rectal cancers. Immunohistochemistry was applied to assess the density of tumour-infiltrating immune cells. For Paper IV, the analyses were restricted to the 584 cases included in the European Prospective Investigation into Cancer (EPIC) cohort, of which the MDCS forms part. Anthropometric measurements were taken at baseline. Cox proportional hazards regression models were applied to study the hazard ratios for survival, and the risk of CRC with particular immune cell compositions.Paper I shows that dense infiltration of B cells is an independent favourable prognostic factor in CRC. Paper II demonstrates that high infiltration of cytotoxic T cells is an independent favourable prognostic factor only in right-sided colon cancer, whereas high infiltration of regulatory T cells is an independent prognostic factor only in rectal cancer. Moreover, re-analysis of the data from paper I revealed that the prognostic impact of B cells is only evident in right-sided tumours.Paper III demonstrates that high expression of programmed cell deaht ligand 1 (PD-L1) on immune cells is an independent favourable prognostic factor only in patients with right-sided and left-sided colon cancer. Paper IV shows that obesity, indicated by several anthropometric factors, is associated with risk of CRC with high infiltration of B cells and cytotoxic T cells but with low infiltration of regulatory T cells in both sexes, albeit with weaker associations in women. Moreover, the results show that obesity is associated with risk of CRC with low PD-L1 expression on immune cells in men, but with high PD-L1 expression on immune cells in women.These results show that the prognostic impact of tumour-infiltrating immune cells in CRC differs according to primary tumour location. It is also demonstrated that obesity might influence the immune microenvironment of CRC. In summary, the findings indicate that primary tumour location, anthropometric factors, and sex are all important factors to include in future studies on the tumour microenvironment of CRC.
|
|
| 3. |
- Murphy, Neil, et al.
(författare)
-
Heterogeneity of Colorectal Cancer Risk Factors by Anatomical Subsite in 10 European Countries : A Multinational Cohort Study
- 2019
-
Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 17:7, s. 1323-1331
-
Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Colorectal cancer located at different anatomical subsites may have distinct etiologies and risk factors. Previous studies that have examined this hypothesis have yielded inconsistent results, possibly because most studies have been of insufficient size to identify heterogeneous associations with precision.Methods: In the European Prospective Investigation into Cancer and Nutrition study, we used multivariable joint Cox proportional hazards models, which accounted for tumorsat different anatomical sites (proximal colon, distal colon, and rectum) as competing risks, to examine the relationships between 14 established/suspected lifestyle, anthropometric, and reproductive/menstrual risk factors with colorectal cancer risk. Heterogeneity across sites was tested using Wald tests.Results: After a median of 14.9 years of follow-up of 521,330 men and women, 6291 colorectal cancer cases occurred. Physical activity was related inversely to proximal colon and distal colon cancer, but not to rectal cancer (P heterogeneity = .03). Height was associated positively with proximal and distal colon cancer only, but not rectal cancer (P heterogeneity = .0001). For men, but not women, heterogeneous relationships were observed for body mass index (P heterogeneity = .008) and waist circumference (P heterogeneity = .03), with weaker positive associations found for rectal cancer, compared with proximal and distal colon cancer. Current smoking was associated with a greater risk of rectal and proximal colon cancer, but not distal colon cancer (P heterogeneity = .05). No heterogeneity by anatomical site was found for alcohol consumption, diabetes, nonsteroidal anti-inflammatory drug use, and reproductive/menstrual factors.Conclusions: The relationships between physical activity, anthropometry, and smoking with colorectal cancer risk differed by subsite, supporting the hypothesis that tumors in different anatomical regions may have distinct etiologies.
|
|
