Colorectal Neoplasia and Vitamin D
Colorectal Neoplasia and Vitamin D
Background The effect of vitamin D on colorectal adenomas may vary with regard to gender, localisation and histological type of the lesion.
Aim To define the role of vitamin D and gender in a Caucasian cohort of subjects undergoing screening colonoscopy after consideration of established risk factors.
Methods One thousand five hundred and thirty-two subjects (813 males, 58.8 ± 9.7 years; 719 females, 59.7 ± 10.7 years) were allocated to tertiles of 25-hydroxyvitamin D3 [25(OH)D3] serum concentrations. The number, localisation, size and histology of the detected colonic lesions were recorded.
Results Among men, no association was found between vitamin D and the total number, size and histological stage of adenomas at any site. In female subjects, less women with adenomas were found in the highest vitamin D tertile (N = 42/239; 17.2%) as compared to the low vitamin D group (N = 60/240; 25.0%; P = 0.035). In particular, the number of women with adenomas in the proximal colon was significantly lower in the highest tertile (N = 21/239, 8.8%) compared to the low vitamin D group (N = 41/240; 17.1%; P = 0.007). The rates at other sites were not different. The inverse association of vitamin D serum concentrations with the presence of adenomas in the proximal colon was maintained after adjustment for potential confounders. In 80 women on vitamin D supplementation, the rate of adenomas was lower compared to those not on supplementation (3/80; 3.8%; vs. 90/719; 12.5%; P = 0.016).
Conclusions A potential preventive effect of vitamin D on colorectal adenomas was found in the proximal colon in women. This observation is supported by further decrease of lesions in the proximal colon of women on vitamin D supplementation.
Besides its well-defined role in calcium and bone homoeostasis, other nonskeletal effects of vitamin D (VD) have received increasing attention. Mostly epidemiological data suggest that lower serum VD concentrations are linked to multiple adverse health-related outcomes such as autoimmune disease, type 2 diabetes, cardiovascular disease, asthma and colon cancer.
Although 1,25(OH)vitamin D3 is the active metabolite binding to the VD nuclear receptor (VDR), determination of the relatively stable precursor molecule 25(OH)vitamin D3 is commonly used to assess VD status. Higher serum concentrations of VD may decrease cancer risk by facilitating apoptosis and differentiation and by inhibiting proliferation, invasion and neoangiogenesis. Epidemiological studies already suggested a lower risk for colorectal adenomas with higher sun exposure more than 30 years ago. A recent meta-analysis suggested a 7% risk reduction for colorectal adenoma per 10 ng/mL increase in VD serum concentration. A 34% risk reduction of the top vs. the lowest quintile of VD serum concentrations was also reported.
The chemopreventive effect of adequate VD serum concentration may be different in men and women and also be different at various anatomical sites of the colon, i.e. proximal colon, distal colon or rectum. In Japanese men, a higher prevalence of distal colonic adenoma was linked to low VD status. A reduced risk for distal adenoma was found particularly in women with higher VD intake in a sigmoidoscopy study.
Molecular interactions have been demonstrated between oestrogen and VD in the colonic epithelium providing a potential molecular explanation for the differences observed between men and women. In particular, oestrogens may increase colonic 1-α-hydroxylase in the colonic epithelium and thereby increasing intracellular availability of the active VD metabolite. In addition, oestrogens appear to increase VD receptor levels in the colonic epithelium.
As these reports suggest a potentially profound effect of sex hormones on the effect of VD in carcinogenesis, we hypothesised that the associations between VD status and colorectal polyps could differ between men and women in a screening cohort. We thus performed a detailed analysis of the data obtained from a Caucasian cohort undergoing screening colonoscopy. We aimed to study the rate, histology and localisation of the colorectal lesions in men and women according to their VD status and after consideration of confounding risk factors such as gender, age, a family history of colorectal cancer (CRC), smoking status and impaired glucose metabolism.
Abstract and Introduction
Abstract
Background The effect of vitamin D on colorectal adenomas may vary with regard to gender, localisation and histological type of the lesion.
Aim To define the role of vitamin D and gender in a Caucasian cohort of subjects undergoing screening colonoscopy after consideration of established risk factors.
Methods One thousand five hundred and thirty-two subjects (813 males, 58.8 ± 9.7 years; 719 females, 59.7 ± 10.7 years) were allocated to tertiles of 25-hydroxyvitamin D3 [25(OH)D3] serum concentrations. The number, localisation, size and histology of the detected colonic lesions were recorded.
Results Among men, no association was found between vitamin D and the total number, size and histological stage of adenomas at any site. In female subjects, less women with adenomas were found in the highest vitamin D tertile (N = 42/239; 17.2%) as compared to the low vitamin D group (N = 60/240; 25.0%; P = 0.035). In particular, the number of women with adenomas in the proximal colon was significantly lower in the highest tertile (N = 21/239, 8.8%) compared to the low vitamin D group (N = 41/240; 17.1%; P = 0.007). The rates at other sites were not different. The inverse association of vitamin D serum concentrations with the presence of adenomas in the proximal colon was maintained after adjustment for potential confounders. In 80 women on vitamin D supplementation, the rate of adenomas was lower compared to those not on supplementation (3/80; 3.8%; vs. 90/719; 12.5%; P = 0.016).
Conclusions A potential preventive effect of vitamin D on colorectal adenomas was found in the proximal colon in women. This observation is supported by further decrease of lesions in the proximal colon of women on vitamin D supplementation.
Introduction
Besides its well-defined role in calcium and bone homoeostasis, other nonskeletal effects of vitamin D (VD) have received increasing attention. Mostly epidemiological data suggest that lower serum VD concentrations are linked to multiple adverse health-related outcomes such as autoimmune disease, type 2 diabetes, cardiovascular disease, asthma and colon cancer.
Although 1,25(OH)vitamin D3 is the active metabolite binding to the VD nuclear receptor (VDR), determination of the relatively stable precursor molecule 25(OH)vitamin D3 is commonly used to assess VD status. Higher serum concentrations of VD may decrease cancer risk by facilitating apoptosis and differentiation and by inhibiting proliferation, invasion and neoangiogenesis. Epidemiological studies already suggested a lower risk for colorectal adenomas with higher sun exposure more than 30 years ago. A recent meta-analysis suggested a 7% risk reduction for colorectal adenoma per 10 ng/mL increase in VD serum concentration. A 34% risk reduction of the top vs. the lowest quintile of VD serum concentrations was also reported.
The chemopreventive effect of adequate VD serum concentration may be different in men and women and also be different at various anatomical sites of the colon, i.e. proximal colon, distal colon or rectum. In Japanese men, a higher prevalence of distal colonic adenoma was linked to low VD status. A reduced risk for distal adenoma was found particularly in women with higher VD intake in a sigmoidoscopy study.
Molecular interactions have been demonstrated between oestrogen and VD in the colonic epithelium providing a potential molecular explanation for the differences observed between men and women. In particular, oestrogens may increase colonic 1-α-hydroxylase in the colonic epithelium and thereby increasing intracellular availability of the active VD metabolite. In addition, oestrogens appear to increase VD receptor levels in the colonic epithelium.
As these reports suggest a potentially profound effect of sex hormones on the effect of VD in carcinogenesis, we hypothesised that the associations between VD status and colorectal polyps could differ between men and women in a screening cohort. We thus performed a detailed analysis of the data obtained from a Caucasian cohort undergoing screening colonoscopy. We aimed to study the rate, histology and localisation of the colorectal lesions in men and women according to their VD status and after consideration of confounding risk factors such as gender, age, a family history of colorectal cancer (CRC), smoking status and impaired glucose metabolism.
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