Int J Cancer. 2017 Jul 15;141(2):336-341. doi: 10.1002/ijc.30740. Epub 2017 Apr 24.
Gromowski T1, Gapska P1, Scott RJ2, Kąklewski K1, Marciniak W3, Durda K1, Lener M1, Górski B1, Cybulski C1, Sukiennicki G1, Kaczmarek K1, Jaworska-Bieniek K1, Paszkowska-Szczur K1, Waloszczyk P4, Lubiński J1,3, Dębniak T1.
- 1 Departmentof Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
- 2 Discipline of Medical Genetics, Faculty of Health, University of Newcastle and Hunter Medical Research Institute, Newcastle, NSW, Australia.
- 3 Read-Gene S.A., Grzepnica, Dobra Szczecińska, Poland.
- 4 Independent Laboratory of Pathology, Zdunomed, Szczecin, Poland.
The first aim of our study was to examine the association between common variants in VDR [rs2228570 (FokI), rs1544410 (BsmI), rs7975232 (ApaI), rs731236 (TaqI) and rs11568820 (Cdx2)] and lung cancer risk in the Polish population. Genotyping and statistical analysis which included Chi-square test with Yates correction and haplotype frequency analysis were performed on a series of 840 consecutively collected lung cancer patients and 920 healthy controls. The second aim was to evaluate the link between serum 25(OH)D concentration and the number of lung cancers in a subgroup of 200 patients. A separate control group that consisted of 400 matched (by age, sex, smoking habits and the season of blood collection) healthy individuals was used to avoid posterior adjustment on the matched variables. Statistical analysis with the use of Chi-square test with Yates was performed.
We found no statistically significant difference in the distribution of the allels of studied VDR variants among cases and controls.
A statistically significant over-representation of VDR haplotypes:
- rs731236_A + rs1544410_T [odds ratio (OR) = 2.43, 95% confidence interval (CI) = 1.11-5.32, p < 0.001],
- rs731236_G + rs1544410_T (OR = 1.54, 95% CI = 1.31-1.81, p < 0.001) and
- rs731236_G + rs1544410_C (OR = 0.04, 95% CI = 0.03-0.07, p < 0.001)
was detected. We found a tendency toward an increased number of lung cancers among individuals with low serum levels of 25(OH)D. To answer the question, whether VDR can be regarded as lung cancer susceptibility gene and low 25(OH)D serum levels is associated with lung cancer occurrences, additional, multicenter study needs to be performed.
PMID: 28411367 DOI: 10.1002/ijc.30740
Lung Cancer 1.4 X more likely if poor VDR, but half as likely if good VDR mutation - Meta-analysis - Jan 2019
The association of vitamin D receptor gene polymorphism with lung cancer risk: an update meta-analysis
Comb Chem High Throughput Screen. 2019 Jan 25. doi: 10.2174/1386207322666190125150557.
Yu ZH1, Chen M1, Zhang QQ1, Hu X2.
1 Department of Oncology, Tongde Hospital of Zhejiang Province, Hangzhou. China.
2 Department of Thoracic Surgery, The Second Hospital of Jiaxing, Jiaxing. China.
The association between vitamin D receptor (VDR) genetic polymorphism and lung cancer risk has been evaluated by previous meta-analyses. Due to emergence of novel studies and inappropriate inclusion of overlapping populations, an update meta-analysis on recent evidences is necessarily needed. We comprehensively searched databases of PubMed, Web of Science and Chinese National Knowledge Infrastructure and finally obtained 7 eligible studies according to the inclusion criteria. Four positions on VDR gene, namely ApaI (rs7975232), BsmI (rs1544410), FokI (rs10735810) and TaqI (rs731236), were considered in this investigation. Data pooling found no significant association of lung cancer risk with ApaI or FokI. In contrast, it was indicated that the BsmI A allele was negatively related to the lung cancer risk, compared with the G allele (OR = 0.51, 95% CI = 0.33-0.79). Individuals with BsmI AA (OR = 0.53, 95% CI = 0.26-1.11) and AG genotypes (OR = 0.46, 95% CI = 0.30-0.71) showed decreased risk of lung cancer, compared with those with GG genotype. Regarding the TaqI polymorphism, the T allele carriers were at increased risk of lung cancer (OR = 1.25, 95% CI = 1.04-1.50). Compared with the TaqI TC+CC genotype, the TT genotype was positively associated with lung cancer risk (OR = 1.42, 95% CI = 1.11-1.82). No publication bias was identified in any of the analysis. In conclusion, VDR genetic polymorphism may be correlated to lung cancer risk. Given limited number of the included studies, more observations are warranted to draw a safer conclusion.