Associations of Diet and Lifestyle with Cell Cycle Biomarkers in the Normal-appearing Colorectal Mucosa of Colorectal Adenoma Patients Open Access

Guang, Xuan (Spring 2019)

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Expression of cell cycle biomarkers of proliferation (Mib-1), differentiation (p21), apoptosis-promotion (BAX) and apoptosis-inhibition (Bcl-2) in the normal-appearing colorectal mucosa were associated with colorectal adenoma. However, there are few data on associations of diet, lifestyle or other factors with expression of these biomarkers in the normal colorectal mucosa of humans.


We measured Mib-1, p21, BAX, Bcl-2 expression in the normal-appearing rectal mucosa, using automated IHC and image analysis, in a subset of 104 participants in a large chemoprevention trial. Diet was assessed using a Block Brief 2000 Food Frequency Questionnaire. Physical activity was assessed by asking participants how much time they spent in moderate or vigorous activities during the past week. Cross-sectional associations of participants’ characteristics with the biomarkers at baseline were assessed using multivariable general linear models to compare adjusted mean biomarker expression across categories of the participants’ characteristics.


Whole crypt adjusted mean BAX expression was 49.4% higher (P=0.11) among patients with higher relative to lower physical activity. Adjusted Bcl-2 expression was 45.3% lower (P=0.05) among patients with higher relative to lower total calcium intakes. Adjusted Mib-1 expression was 19.4% lower (P=0.10) among patients with higher relative to lower fruit intakes. Adjusted P21 expression was 37.5% higher (P=0.18) among patients with higher relative to lower serum 25-OH vitamin D concentrations.       


Our findings support 1) a possible direct association of physical activity with BAX expression; 2) an inverse association of total calcium intake with Bcl-2 expression; 3) inverse associations of fruit intake with Mib-1 expression; and 4) a direct association of serum 25-OH vitamin D concentrations with p21 expression in the normal-appearing colorectal mucosa of sporadic colorectal adenoma patients.

Table of Contents

Introduction. 1

Methods. 2

Immunohistochemistry Protocol 4

Statistical Analysis. 5

Results. 6

Apoptosis-promoting (BAX) 7

Apoptosis-inhibiting (Bcl- 2) 8

Proliferation (Mib-1) 8

Differentiation (p21) 9

Discussion. 10

Apoptosis. 11

Proliferation. 12

Differentiation. 13

Strengths and Limitations. 13

Conclusions. 14

References 15

Figure. 19

Tables. 20

Supplements 34

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