Estigators and cross-checked to reach an agreement. The following data was recorded in detail: the last name of the very first author, publication year, the country exactly where the study was performed, study design, sex, age at baseline, study period, measure and selection of exposure, sample size (situations and controls or cohort size), description of crucial baseline confounders, major cancer location, and outcomes of interest. Articles have been categorized depending on the results of interest: major CDK7 Inhibitor Biological Activity outcome (HNC incidence), secondary outcome (HNC mortality and HNC survival). Articles reportingFrontiers in Immunology | www.frontiersin.orgFebruary 2021 | Volume 12 | ArticlePu et al.Vitamin D in HNCRESULTSTotal searches yielded 4,921 entries. Just after the removal of 1,482 duplicates, three,439 titles and abstracts were assessed; 176 articles appeared to be potentially enrolled inside the review. Following a full-text critique, 160 articles were excluded, leaving 16 articles for final analyses, such as four IL-23 Inhibitor list research on VDR gene polymorphisms, nine on blood 25-OHD levels, and 3 on vitamin D intake. A flow diagram of our literature search approach was shown in Figure 1. List of excluded articles was provided in Supplementary Table 2.Study CharacteristicsSixteen observational studies were incorporated in our meta-analysis (245, 414), like nine case ontrol and seven cohort research that have been published involving 2000 and 2018. Of these 16 studies, ten were performed in Europe, three in North America, and 3 in Asia-Pacific. Inside the 81,908 participants, two,270 participants possessed the facts of VDR gene polymorphism reports, 73,004 participants had the info of 25hydroxyvitamin D concentrations, and 6634 participants derived in the investigations of vitamin D intake.Of these participants, 5272 HNC patients have been enrolled, which includes 1,064 VDR gene polymorphism, 2,146 25-hydroxyvitamin D concentrations, and two,062 vitamin D intake. Two cohort research and a nested case ontrol study incorporated only males. In most research, participants had been 40 years or older. Six studies have been population-based, nine studies were hospital-based, and one particular study included overall health experts. Most research analyzed the risk of HNC by comparing the highest towards the lowest fifth, fourth, or third of 25-hydroxyvitamin D or vitamin D intake. The VDR gene was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) in chosen research. Radioimmunoassay, automated immunoassay, and chromatographic methods have been utilized to detect the concentrations of 25-hydroxyvitamin D. All research of vitamin D intake were investigated on food frequency questionnaires. Table 1 summarized all the integrated research, and Supplementary Table three displayed the details of those studies. A total of 4 publications reported the association amongst VDR gene polymorphism and also the risk of HNC, all of which have been casecontrol studies. Two studies focused on Asians, as well as the other two studies focused on Caucasians. The following 4 VDR SNPs have been studied: TaqI (rs731236, alleles t/T), FokI (rs2228570, alleles f/F), and BsmI (rs1544410, alleles B/b). 3 research on FokI polymorphism incorporated 1,000 sufferers and 1,119 controls, 3 research on TaqIFIGURE 1 | Search technique and final incorporated and excluded research.Frontiers in Immunology | www.frontiersin.orgFebruary 2021 | Volume 12 | ArticlePu et al.Vitamin D in HNCTABLE 1 | Summary characteristics of incorporated research. Qualities Cohort studies Case.