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
Department of Nutrition, Harvard School of Public Health, Boston, MA, United States.
Department of Epidemiology, Harvard School of Public Health, Boston, MA, United States.
Gut. 2016 Feb;65(2):296-304. doi: 10.1136/gutjnl-2014-308852. Epub 2015 Jan 15.
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.
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.
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 trend<0.001), but not risk of tumour with lower-level reaction (p for trend>0.50). 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).
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.
有证据表明维生素D和抗肿瘤免疫对结直肠癌风险具有保护作用。肿瘤微环境中的免疫细胞可将25-羟基维生素D[25(OH)D]转化为具有生物活性的1α,25-二羟基维生素D3，其作为自分泌和旁分泌因子影响肿瘤细胞和免疫细胞。因此，我们推测维生素D与结直肠癌风险之间的负相关关系在免疫反应水平高的癌症中可能比在免疫反应水平低的癌症中更强。
我们在护士健康研究和卫生专业人员随访研究中利用分子病理流行病学数据库设计了一项巢式病例对照研究（318例直肠癌和结肠癌病例以及624例匹配对照）。采用多变量条件逻辑回归根据淋巴细胞反应程度、肿瘤浸润T细胞（CD3+、CD8+、CD45RO+(PTPRC)和FOXP3+细胞）、微卫星不稳定性或CpG岛甲基化表型评估血浆25(OH)D与肿瘤亚型的关联。
血浆25(OH)D与结直肠癌的关联因肿瘤内腺周反应程度而异（异质性p=0.001）；高25(OH)D与高水平反应肿瘤的较低风险相关（比较最高三分位数与最低三分位数：OR 0.10；95%CI 0.03至0.35；趋势p<0.001），但与低水平反应肿瘤的风险无关（趋势p>0.50）。根据CD3+T细胞密度，25(OH)D与肿瘤亚型的关联存在统计学上无显著差异（异质性p=0.03；调整后的统计学显著性水平α=0.006）。
高血浆25(OH)D水平与免疫反应强烈的结直肠癌风险较低相关，支持维生素D通过肿瘤-宿主相互作用在癌症免疫预防中的作用。
