Vitamin D-Related Gene Polymorphisms, Plasma 25-Hydroxy-Vitamin D, Cigarette Smoke and Non-Small Cell Lung Cancer (NSCLC) Risk.
Epidemiological studies regarding the relationship between vitamin D, genetic polymorphisms in the vitamin D metabolism, cigarette smoke and non-small cell lung cancer (NSCLC) risk have not been investigated comprehensively. To search for additional evidence, the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and radioimmunoassay method were utilized to evaluate 5 single-nucleotide polymorphisms (SNPs) in vitamin D receptor (VDR), 6 SNPs in 24-hydroxylase (CYP24A1), 2 SNPs in 1α-hydroxylase (CYP27B1) and 2 SNPs in vitamin D-binding protein (group-specific component, GC) and plasma vitamin D levels in 426 NSCLC cases and 445 controls from China. Exposure to cigarette smoke was ascertained through questionnaire information. Multivariable linear regressions and mixed effects models were used in statistical analysis. The results showed that Reference SNP rs6068816 in CYP24A1, rs1544410 and rs731236 in VDR and rs7041 in GC were statistically significant in relation to reduction in NSCLC risk (p < 0.001-0.05). No significant connection was seen between NSCLC risk and overall plasma 25-hydroxyvitamin D [25(OH)D] concentrations, regardless of smoking status. However, the mutation genotype of CYP24A1 rs6068816 and VDR rs1544410 were also significantly associated with increased 25(OH)D levels only in both the smoker and non-smoker cases (p < 0.01-0.05). Meanwhile, smokers and non-smokers with mutated homozygous rs2181874 in CYP24A1 had significantly increased NSCLC risk (odds ratio (OR) = 2.14, 95% confidence interval (CI) 1.47-3.43; p = 0.031; OR = 3.57, 95% CI 2.66-4.74; p = 0.019, respectively). Smokers with mutated homozygous rs10735810 in VDR had significantly increased NSCLC risk (OR = 1.93, 95% CI 1.41-2.76; p = 0.015). However, smokers with mutated homozygous rs6068816 in CYP24A1 had significantly decreased NSCLC risk (OR = 0.43, 95% CI 0.27-1.02; p = 0.006); and smokers and non-smokers with mutated homozygous rs1544410 in VDR had significantly decreased NSCLC risk (OR = 0.51, 95% CI 0.34-1.17; p = 0.002; OR = 0.26, 95% CI 0.20-0.69; p = 0.001, respectively). There are significant joint effects between smoking and CYP24A1 rs2181874, CYP24A1 rs6068816, VDR rs10735810, and VDR rs1544410 (p < 0.01-0.05). Smokers with mutated homozygous rs10735810 in VDR had significantly increased NSCLC risk (OR = 1.93, 95% CI 1.41-2.76; p = 0.015). In summary, the results suggested that the lower the distribution of vitamin D concentration, the more the genetic variations in CYP24A1, VDR and GC genes may be associated with NSCLC risk. In addition, there are significant joint associations of cigarette smoking and vitamin D deficiency on NSCLC risk.
School of Life Sciences, The Engineering Research Center of Sustainable Development and Utilization of Biomass Energy, Ministry of Education, Yunnan Normal University, Kunming 650500, China. xiayu98wu@163.com.
Xiayu
X
Wu
Yunnan Key laboratory for Basic Research on Bone and Joint Diseases, Yunnan Stem Cell Translational Research Center, Kunming University, Kunming 650500, China. jojo1988509@163.com.
Jiaoni
J
Cheng
Hospital of Kunming Medical College, Kunming 650101, China. yangky2214@163.com.
Kaiyun
K
Yang
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics; D000368:Aged; D000483:Alleles; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics; D012306:Risk; D012907:Smoking; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014809:Vitamin D-Binding Protein / Q000235:genetics; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics
D018167:Receptors, Calcitriol; D014809:Vitamin D-Binding Protein; D014807:Vitamin D; C104450:25-hydroxyvitamin D; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase
NSCLC; gene polymorphisms; risk; smoke; vitamin D
Nephron Clin Pract. 2013;124(1-2):17-22
24029861
Chin J Cancer Res. 2011 Mar;23(1):33-7
23467735
Gastroenterology. 2009 Sep;137(3):834-40, 840.e1-3
19454285
Eur J Endocrinol. 2005 Jan;152(1):39-45
15762185
Cancer Causes Control. 2012 Sep;23(9):1443-9
22740028
Zhonghua Liu Xing Bing Xue Za Zhi. 2015 Oct;36(10):1047-52
26837341
Clin J Oncol Nurs. 2011 Oct;15(5):557-60
21951742
Biochimie. 2003 Nov;85(11):1073-82
14726014
J Expo Sci Environ Epidemiol. 2013 Jan-Feb;23 (1):94-100
22968348
J Steroid Biochem Mol Biol. 2014 Oct;144 Pt A:91-5
24120915
Osteoporos Int. 2002 Jan;13(1):83-8
11883410
Clin Chim Acta. 2006 Oct;372(1-2):33-42
16697362
Mutat Res. 2001 Mar;488(1):65-76
11223405
Int J Cancer. 2013 Jun 1;132(11):2520-7
23169318
Interact Cardiovasc Thorac Surg. 2012 Feb;14(2):151-5
22159250
Lung Cancer. 2014 Dec;86(3):297-303
25456734
Gastroenterology. 2016 Aug;151(2):351-363.e28
27094239
Cancer Chemother Pharmacol. 2006 Jan;57(2):234-40
16180015
Radiol Clin North Am. 2012 Sep;50(5):863-76
22974775
Clin Biochem. 2009 Oct;42(15):1549-56
19631201
Am J Hum Genet. 2004 Jan;74(1):106-20
14681826
Tumour Biol. 2014 Feb;35(2):1323-30
24068566
Cancer. 2015 Jun 15;121(12):1949-56
25731953
J Clin Oncol. 2008 Dec 1;26(34):5596-602
18936471
Asian Pac J Cancer Prev. 2015;16(8):3339-44
25921141
Eur J Clin Nutr. 1999 Dec;53(12):920-6
10602348
Endocrinology. 1999 Jul;140(7):3303-10
10385427
Carcinogenesis. 2013 Mar;34(3):587-94
23180655
Int J Mol Sci. 2015 Oct 15;16(10 ):24369-86
26501255
Am J Respir Crit Care Med. 1997 May;155(5):1770-6
9154890
Oncotarget. 2015 Feb 10;6(4):2573-82
25544771
Cancer Biomark. 2015;15(5):663-8
26406955
Arch Biochem Biophys. 2012 Jul 1;523(1):9-18
22100522
Cancer Causes Control. 2014 Jul;25(7):819-27
24748579
J Thorac Oncol. 2014 Apr;9(4):473-82
24736069
Front Biosci (Schol Ed). 2011 Jun 01;3:1463-77
21622282
Autophagy. 2014;10(12):2346-61
25629933
Cancer Chemother Pharmacol. 2013 May;71(5):1173-82
23435876
Eur J Cancer Prev. 1999 Oct;8(5):441-7
10548400
Med Sci Monit. 2009 Aug;15(8):BR232-42
19644412
J Cancer Res Ther. 2007 Oct-Dec;3(4):225-30
18270398
Cancer Epidemiol Biomarkers Prev. 2008 Nov;17(11):3274-8
18990771
PLoS Med. 2008 Sep 30;5(9):e185
18788891
Eur J Cardiothorac Surg. 2011 Jul;40(1):83-90
21169031
PLoS One. 2015 Mar 23;10(3):e0117574
25799011
Cancer Immunol Immunother. 1995 Jul;41(1):37-45
7641218
Lung Cancer. 2007 Mar;55(3):263-70
17207891
Int J Clin Exp Med. 2012;5(1):72-9
22328951
Mol Cell Endocrinol. 2012 May 15;355(1):153-61
22386975
J Lipid Res. 2014 Jan;55(1):13-31
23564710
Nat Rev Immunol. 2009 May;9(5):377-84
19330016
Gynecol Endocrinol. 2015;31(12):976-9
26422783
BJU Int. 2009 Oct;104(7):909-14
19426195
Int J Cancer. 2016 May 1;138(9):2118-26
26650177
Clin Lung Cancer. 2013 Jul;14(4):433-9
23522953
Nutrition. 2010 Mar;26(3):255-62
20004077
Cancer Causes Control. 2015 Feb;26(2):205-18
25488826
Cancer Epidemiol Biomarkers Prev. 2010 Feb;19(2):525-36
20086113
Regul Toxicol Pharmacol. 2013 Oct;67(1):13-26
23764305
Genes Cancer. 2013 Nov;4(11-12):524-34
24386512
Ann Epidemiol. 2009 Feb;19(2):73-8
18329892
Nat Genet. 1999 Jul;22(3):231-8
10391209
Mol Biol Rep. 2014 Oct;41(10):6545-53
24996287
Nat Genet. 2012 Jul 15;44(8):895-9
22797725
CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
21296855
Exp Dermatol. 2010 Dec;19(12):1103-5
20812960
Tob Control. 2008 Aug;17(4):248-55
18483129
Cancer Causes Control. 2015 Feb;26(2):187-203
25421379
J Hum Genet. 2013 Nov;58(11):749-51
23924835
Br J Nurs. 2016 Aug 11;25(15):846-51
27523756
Lancet. 2010 Jul 17;376(9736):180-8
20541252
J Clin Endocrinol Metab. 1994 Aug;79(2):554-60
8045976
J Clin Oncol. 2007 Feb 10;25(5):479-85
17290055
Endocr J. 2014;61(2):133-41
24200978
Oncotarget. 2016 Jan 5;7(1):995-1013
26654942
Am J Clin Nutr. 2015 Jun;101(6):1206-15
25904602
Clin Cancer Res. 2011 Feb 15;17 (4):817-26
21169243