Plasma 25-hydroxyvitamin D and colorectal cancer risk according to tumour immunity status

Mingyang Song, Reiko Nishihara, Molin Wang, Andrew T. Chan, Zhi Rong Qian, Kentaro Inamura, Xuehong Zhang, Kimmie Ng, Sun A. Kim, Kosuke Mima, Yasutaka Sukawa, Katsuhiko Nosho, Charles S. Fuchs, Edward L. Giovannucci, Kana Wu, Shuji Ogino

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Objective Evidence suggests protective effects of vitamin D and antitumour immunity on colorectal cancer risk. Immune cells in tumour microenvironment can convert 25-hydroxyvitamin D [25(OH)D] to bioactive 1α,25- dihydroxyvitamin D3, which influences neoplastic and immune cells as an autocrine and paracrine factor. Thus, we hypothesised that the inverse association between vitamin D and colorectal cancer risk might be stronger for cancers with high-level immune response than those with low-level immune response. Design We designed a nested case-control study (318 rectal and colon carcinoma cases and 624 matched controls) within the Nurses' Health Study and Health Professionals Follow-up Study using molecular pathological epidemiology database. Multivariable conditional logistic regression was used to assess the association of plasma 25 (OH)D with tumour subtypes according to the degree of lymphocytic reaction, tumour-infiltrating T cells (CD3+, CD8+, CD45RO+ (PTPRC) and FOXP3+ cells), microsatellite instability or CpG island methylator phenotype. Results The association of plasma 25(OH)D with colorectal carcinoma differed by the degree of intratumoural periglandular reaction (p for heterogeneity=0.001); high 25(OH)D was associated with lower risk of tumour with high-level reaction (comparing the highest versus lowest tertile: OR 0.10; 95% CI 0.03 to 0.35; p for trend0.50). A statistically non-significant difference was observed for the associations of 25(OH)D with tumour subtypes according to CD3+ T cell density (p for heterogeneity=0.03; adjusted statistical significance level of α=0.006). Conclusions High plasma 25(OH)D level is associated with lower risk of colorectal cancer with intense immune reaction, supporting a role of vitamin D in cancer immunoprevention through tumour-host interaction.

Original languageEnglish
Pages (from-to)296-304
Number of pages9
JournalGut
Volume65
Issue number2
DOIs
Publication statusPublished - 2016 Feb 1
Externally publishedYes

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Colorectal Neoplasms
Immunity
Neoplasms
Vitamin D
T-Lymphocytes
Microsatellite Instability
CpG Islands
Tumor Microenvironment
Molecular Epidemiology
Calcitriol
Health
25-hydroxyvitamin D
Case-Control Studies
Colon
Cell Count
Logistic Models
Nurses
Databases
Carcinoma
Phenotype

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Song, M., Nishihara, R., Wang, M., Chan, A. T., Qian, Z. R., Inamura, K., ... Ogino, S. (2016). Plasma 25-hydroxyvitamin D and colorectal cancer risk according to tumour immunity status. Gut, 65(2), 296-304. https://doi.org/10.1136/gutjnl-2014-308852

Plasma 25-hydroxyvitamin D and colorectal cancer risk according to tumour immunity status. / Song, Mingyang; Nishihara, Reiko; Wang, Molin; Chan, Andrew T.; Qian, Zhi Rong; Inamura, Kentaro; Zhang, Xuehong; Ng, Kimmie; Kim, Sun A.; Mima, Kosuke; Sukawa, Yasutaka; Nosho, Katsuhiko; Fuchs, Charles S.; Giovannucci, Edward L.; Wu, Kana; Ogino, Shuji.

In: Gut, Vol. 65, No. 2, 01.02.2016, p. 296-304.

Research output: Contribution to journalArticle

Song, M, Nishihara, R, Wang, M, Chan, AT, Qian, ZR, Inamura, K, Zhang, X, Ng, K, Kim, SA, Mima, K, Sukawa, Y, Nosho, K, Fuchs, CS, Giovannucci, EL, Wu, K & Ogino, S 2016, 'Plasma 25-hydroxyvitamin D and colorectal cancer risk according to tumour immunity status', Gut, vol. 65, no. 2, pp. 296-304. https://doi.org/10.1136/gutjnl-2014-308852
Song M, Nishihara R, Wang M, Chan AT, Qian ZR, Inamura K et al. Plasma 25-hydroxyvitamin D and colorectal cancer risk according to tumour immunity status. Gut. 2016 Feb 1;65(2):296-304. https://doi.org/10.1136/gutjnl-2014-308852
Song, Mingyang ; Nishihara, Reiko ; Wang, Molin ; Chan, Andrew T. ; Qian, Zhi Rong ; Inamura, Kentaro ; Zhang, Xuehong ; Ng, Kimmie ; Kim, Sun A. ; Mima, Kosuke ; Sukawa, Yasutaka ; Nosho, Katsuhiko ; Fuchs, Charles S. ; Giovannucci, Edward L. ; Wu, Kana ; Ogino, Shuji. / Plasma 25-hydroxyvitamin D and colorectal cancer risk according to tumour immunity status. In: Gut. 2016 ; Vol. 65, No. 2. pp. 296-304.
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abstract = "Objective Evidence suggests protective effects of vitamin D and antitumour immunity on colorectal cancer risk. Immune cells in tumour microenvironment can convert 25-hydroxyvitamin D [25(OH)D] to bioactive 1α,25- dihydroxyvitamin D3, which influences neoplastic and immune cells as an autocrine and paracrine factor. Thus, we hypothesised that the inverse association between vitamin D and colorectal cancer risk might be stronger for cancers with high-level immune response than those with low-level immune response. Design We designed a nested case-control study (318 rectal and colon carcinoma cases and 624 matched controls) within the Nurses' Health Study and Health Professionals Follow-up Study using molecular pathological epidemiology database. Multivariable conditional logistic regression was used to assess the association of plasma 25 (OH)D with tumour subtypes according to the degree of lymphocytic reaction, tumour-infiltrating T cells (CD3+, CD8+, CD45RO+ (PTPRC) and FOXP3+ cells), microsatellite instability or CpG island methylator phenotype. Results The association of plasma 25(OH)D with colorectal carcinoma differed by the degree of intratumoural periglandular reaction (p for heterogeneity=0.001); high 25(OH)D was associated with lower risk of tumour with high-level reaction (comparing the highest versus lowest tertile: OR 0.10; 95{\%} CI 0.03 to 0.35; p for trend0.50). A statistically non-significant difference was observed for the associations of 25(OH)D with tumour subtypes according to CD3+ T cell density (p for heterogeneity=0.03; adjusted statistical significance level of α=0.006). Conclusions High plasma 25(OH)D level is associated with lower risk of colorectal cancer with intense immune reaction, supporting a role of vitamin D in cancer immunoprevention through tumour-host interaction.",
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T1 - Plasma 25-hydroxyvitamin D and colorectal cancer risk according to tumour immunity status

AU - Song, Mingyang

AU - Nishihara, Reiko

AU - Wang, Molin

AU - Chan, Andrew T.

AU - Qian, Zhi Rong

AU - Inamura, Kentaro

AU - Zhang, Xuehong

AU - Ng, Kimmie

AU - Kim, Sun A.

AU - Mima, Kosuke

AU - Sukawa, Yasutaka

AU - Nosho, Katsuhiko

AU - Fuchs, Charles S.

AU - Giovannucci, Edward L.

AU - Wu, Kana

AU - Ogino, Shuji

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N2 - Objective Evidence suggests protective effects of vitamin D and antitumour immunity on colorectal cancer risk. Immune cells in tumour microenvironment can convert 25-hydroxyvitamin D [25(OH)D] to bioactive 1α,25- dihydroxyvitamin D3, which influences neoplastic and immune cells as an autocrine and paracrine factor. Thus, we hypothesised that the inverse association between vitamin D and colorectal cancer risk might be stronger for cancers with high-level immune response than those with low-level immune response. Design We designed a nested case-control study (318 rectal and colon carcinoma cases and 624 matched controls) within the Nurses' Health Study and Health Professionals Follow-up Study using molecular pathological epidemiology database. Multivariable conditional logistic regression was used to assess the association of plasma 25 (OH)D with tumour subtypes according to the degree of lymphocytic reaction, tumour-infiltrating T cells (CD3+, CD8+, CD45RO+ (PTPRC) and FOXP3+ cells), microsatellite instability or CpG island methylator phenotype. Results The association of plasma 25(OH)D with colorectal carcinoma differed by the degree of intratumoural periglandular reaction (p for heterogeneity=0.001); high 25(OH)D was associated with lower risk of tumour with high-level reaction (comparing the highest versus lowest tertile: OR 0.10; 95% CI 0.03 to 0.35; p for trend0.50). A statistically non-significant difference was observed for the associations of 25(OH)D with tumour subtypes according to CD3+ T cell density (p for heterogeneity=0.03; adjusted statistical significance level of α=0.006). Conclusions High plasma 25(OH)D level is associated with lower risk of colorectal cancer with intense immune reaction, supporting a role of vitamin D in cancer immunoprevention through tumour-host interaction.

AB - Objective Evidence suggests protective effects of vitamin D and antitumour immunity on colorectal cancer risk. Immune cells in tumour microenvironment can convert 25-hydroxyvitamin D [25(OH)D] to bioactive 1α,25- dihydroxyvitamin D3, which influences neoplastic and immune cells as an autocrine and paracrine factor. Thus, we hypothesised that the inverse association between vitamin D and colorectal cancer risk might be stronger for cancers with high-level immune response than those with low-level immune response. Design We designed a nested case-control study (318 rectal and colon carcinoma cases and 624 matched controls) within the Nurses' Health Study and Health Professionals Follow-up Study using molecular pathological epidemiology database. Multivariable conditional logistic regression was used to assess the association of plasma 25 (OH)D with tumour subtypes according to the degree of lymphocytic reaction, tumour-infiltrating T cells (CD3+, CD8+, CD45RO+ (PTPRC) and FOXP3+ cells), microsatellite instability or CpG island methylator phenotype. Results The association of plasma 25(OH)D with colorectal carcinoma differed by the degree of intratumoural periglandular reaction (p for heterogeneity=0.001); high 25(OH)D was associated with lower risk of tumour with high-level reaction (comparing the highest versus lowest tertile: OR 0.10; 95% CI 0.03 to 0.35; p for trend0.50). A statistically non-significant difference was observed for the associations of 25(OH)D with tumour subtypes according to CD3+ T cell density (p for heterogeneity=0.03; adjusted statistical significance level of α=0.006). Conclusions High plasma 25(OH)D level is associated with lower risk of colorectal cancer with intense immune reaction, supporting a role of vitamin D in cancer immunoprevention through tumour-host interaction.

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