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Hamada, Tsuyoshi,Liu, Li,Nowak, Jonathan A.,Mima, Kosuke,Cao, Yin,Ng, Kimmie,Twombly, Tyler S.,Song, Mingyang,Jung, Seungyoun,Dou, Ruoxu,Masugi, Yohei,Kosumi, Keisuke,Shi, Yan,da Silva, Annacarolina,G Elsevier 2018 European journal of cancer Vol.103 No.-
<P><B>Abstract</B></P> <P><B>Background</B></P> <P>High-level plasma 25-hydroxyvitamin D [25(OH)D] has been associated with lower colorectal cancer incidence and mortality. Considering evidence indicating immunomodulatory effects of vitamin D, we hypothesised that survival benefits from high systemic vitamin D level might be stronger for colorectal carcinoma with lower immune response to tumour.</P> <P><B>Methods</B></P> <P>Using 869 colon and rectal cancer cases within the Nurses' Health Study and Health Professionals Follow-up Study, we assessed the prognostic association of postdiagnosis 25(OH)D score [derived from diet and lifestyle variables to predict plasma 25(OH)D level] in strata of levels of histopathologic lymphocytic reaction. The Cox proportional hazards regression model was adjusted for potential confounders, including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, <I>PTGS2</I> (cyclooxygenase-2) expression and <I>KRAS</I>, <I>BRAF</I> and <I>PIK3CA</I> mutations.</P> <P><B>Results</B></P> <P>The association of postdiagnosis 25(OH)D score with colorectal cancer-specific mortality differed by levels of peritumoural lymphocytic reaction (<I>p</I> <SUB>interaction</SUB> = 0.001). Multivariable-adjusted mortality hazard ratios for a quintile-unit increase of 25(OH)D score were 0.69 [95% confidence interval (CI), 0.54–0.89] in cases with negative/low peritumoural lymphocytic reaction, 1.08 (95% CI, 0.93–1.26) in cases with intermediate peritumoural reaction and 1.25 (95% CI, 0.75–2.09) in cases with high peritumoural reaction. The survival association of the 25(OH)D score did not significantly differ by Crohn's-like lymphoid reaction, intratumoural periglandular reaction or tumour-infiltrating lymphocytes.</P> <P><B>Conclusions</B></P> <P>The association between the 25(OH)D score and colorectal cancer survival is stronger for carcinomas with lower peritumoural lymphocytic reaction. Our results suggesting interactive effects of vitamin D and immune response may contribute to personalised dietary and lifestyle intervention strategies.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The survival association of vitamin D is stronger in cancer with fewer lymphocytes. </LI> <LI> Vitamin D and peritumoural lymphocytes interact to modify cancer progression. </LI> <LI> Vitamin D may exert anti-tumour immune-enhancing effects. </LI> <LI> Peritumoural lymphocytic reaction may be a biomarker for benefits from vitamin D. </LI> <LI> Our data support immunomodulatory lifestyle interventions for cancer patients. </LI> </UL> </P>