The purpose of this study was to investigate the potential role of the cyclin D1 gene G870A polymorphism in the likelihood of the development of lung cancer and the overall survival of lung cancer patients in the North Indian population.
Methods:
The study consisted of 353 lung cancer cases and 351 age- and gender-matched healthy controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLPP) was done for the CCND1 gene. The association analysis was done using the multiple linear regression, and the survival analysis was done using the Kaplan-Meier and the Cox regression models.
Results:
The GA genotype was associated with an increased risk for overall lung cancer (odds ratio [OR] = 1.63; p = 0.01). Combined variant genotype showed a significant association for overall lung cancer (OR 1.50; p = 0.03). In addition, smokers with the carrier genotype of CCND1 were found to have a significantly higher risk for lung cancer (OR 1.57; p = 0.04). No significant correlation was observed between the overall survival of lung cancer patients and CCND1 polymorphism. However, on stratifying the subjects on the basis of histology, it was evident that small-cell lung cancer (SCLC) patients carrying the mutant (AA) genotype showed nearly a fivefold increased mortality rate compared to the wild (GG) genotype (p = 0.03).
Conclusions:
Our results suggest that polymorphic CCND1 may increase the risk of lung cancer in smokers from North India, and it may be associated with the overall survival of SCLC patients.
BrayF. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 11. Lyon, France: International Agency for Research on Cancer; 2013. http://globocan.iarc.fr, accessed on day/month/year. Accessed November 23, 2017.
2.
WoganGNHechtSSFeltonJSConneyAHLoebLA. Environmental and chemical carcinogenesis. Semin Cancer Biol. 2004;14(6):473-486.
3.
AmosCIXuWSpitzMR. Is there a genetic basis for lung cancer susceptibility?Recent Results Cancer Res. 1999;151:3-12.
4.
ShahPPSinghAPSinghMet al. Interaction of cytochrome P4501A1 genotypes with other risk factors and susceptibility to lung cancer. Mutat Res. 2008;639(1-2):1-10.
5.
ParkMTLeeSJ. Cell cycle and cancer. J Biochem Mol Biol. 2003;36(1):60-65.
6.
CaputiMGroegerAMEspositoVet al. Prognostic role of cyclin D1 in lung cancer. Relationship to proliferating cell nuclear antigen. Am J Respir Cell Mol Biol. 1999;20(4):746-750.
7.
KnudsenKEDiehlJAHaimanCAKnudsenES. Cyclin D1: polymorphism, aberrant splicing and cancer risk. Oncogene. 2006;25(11):1620-1628.
8.
GautschiORatschillerDGuggerMBetticherDCHeighwayJ. Cyclin D1 in non-small cell lung cancer: a key driver of malignant transformation. Lung Cancer. 2007;55(1):1-14.
9.
ZhouCAnHHuMet al. The cyclin D1 (CCND1) G870A polymorphism and lung cancer susceptibility: a meta-analysis. Tumour Biol. 2013;34(6):3831-3837.
10.
GuptaVKFeberAXiLet al. Association between CCND1 G/A870 polymorphism, allele-specific amplification, cyclin D1 expression, and survival in esophageal and lung carcinoma. Clin Cancer Res. 2008;14(23):7804-7812.
11.
ShuXOMooreDBCaiQet al. Association of cyclin D1 genotype with breast cancer risk and survival. Cancer Epidemiol Biomarkers Prev. 2005;14(1):91-97.
12.
GautschiOHugliBZieglerAet al. Cyclin D1 (CCND1) A870G gene polymorphism modulates smoking-induced lung cancer risk and response to platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients. Lung Cancer. 2006;51(3):303-311.
13.
PanovSZ. Molecular biology of the lung cancer. Radiol Oncol. 2005;39(3):197-210.
14.
TashiroETsuchiyaAImotoM. Functions of cyclin D1 as an oncogene and regulation of cyclin D1 expression. Cancer Sci. 2007;98(5):629-635.
15.
BuchSCDiergaardeBNukuiTet al. Genetic variability in DNA repair and cell cycle control pathway genes and risk of smoking-related lung cancer. Mol Carcinog. 2012;51(S1)(Suppl 1):E11-E20.
16.
HoYSChenCHWangYJet al. Tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces cell proliferation in normal human bronchial epithelial cells through NFkappaB activation and cyclin D1 up-regulation. Toxicol Appl Pharmacol. 2005;205(2):133-148.
17.
SodhiKKBahlCSinghNBeheraDSharmaS. Functional genetic variants in pre-miR-146a and 196a2 genes are associated with risk of lung cancer in North Indians. Future Oncol. 2015;11(15):2159-2173.
18.
SatinderKChanderSRPushpinderKInduGVeenaJ. Cyclin D1 (G870A) polymorphism and risk of cervix cancer: a case control study in north Indian population. Mol Cell Biochem. 2008;315(1-2):151-157.
19.
KumariABahlCSinghNBeheraDSharmaS. Association of p53 codon 72 polymorphism and survival of North Indian lung cancer patients treated with platinum-based chemotherapy. Mol Biol Rep. 2016;43(12):1383-1394.
20.
SobtiRCKaurPKaurSet al. Effects of cyclin D1 (CCND1) polymorphism on susceptibility to lung cancer in a North Indian population. Cancer Genet Cytogenet. 2006;170(2):108-114.
21.
HongYEuKWSeow-ChoenFFook-ChongSCheahPY. GG genotype of cyclin D1 G870A polymorphism is associated with increased risk and advanced colorectal cancer in patients in Singapore. Eur J Cancer. 2005;41(7):1037-1044.
22.
FengBJHuangWShugartYYet al. Genome-wide scan for familial nasopharyngeal carcinoma reveals evidence of linkage to chromosome 4. Nat Genet. 2002;31(4):395-399.
23.
CatarinoRJBredaECoelhoVet al. Association of the A870G cyclin D1 gene polymorphism with genetic susceptibility to nasopharyngeal carcinoma. Head Neck. 2006;28(7):603-608.
24.
ChienCRSuSYCohenLLinHWLeeRTShihYC. Use of Chinese medicine among survivors of nasopharyngeal carcinoma in Taiwan: a population-based study. Integr Cancer Ther. 2012;11(3):221-231.
25.
WangLHabuchiTTakahashiTet al. Cyclin D1 gene polymorphism is associated with an increased risk of urinary bladder cancer. Carcinogenesis. 2002;23:257e64.
26.
JiangJWangJSuzukiSet al. Elevated risk of colorectal cancer associated with AA genotype of the cyclin D1 A870G polymorphism in an Indian population. J Cancer Res Clin Oncol. 2006;132:193e9.
27.
QiulingSYuxinZSuhuaZChengXShuguangLFengshengH. Cyclin D1 gene polymorphism and susceptibility to lung cancer in a Chinese population. Carcinogenesis. 2003;24(9):1499-1503.
28.
McKayJAGithangaJIndaloAet al. Distinct differences in a cyclin D1 single nucleotide polymorphism between ethnic groups. GeneScreen. 2001;1(3):139-142.
29.
KripplPLangsenlehnerURennerWet al. The 870G>A polymorphism of the cyclin D1 gene is not associated with breast cancer. Breast Cancer Res Treat. 2003;82(3):165-168.
30.
McKayJADouglasJJRossVGCurranSMurrayGICassidyJ; Aberdeen Colorectal Initiative. Cyclin D1 protein expression and gene polymorphism in colorectal cancer. Int J Cancer. 2000;88(1):77-81.
31.
LinYCYehCJWangLHLeeCWChenCH. The effect of CCND1 +870A>G and VEGF +936C>T polymorphisms on oral cancer development and disease-free survival in a Taiwan population. Oral Oncol. 2012;48(6):535-540.
32.
HsiaTCLiuCJLinCHet al. Interaction of CCND1 genotype and smoking habit in Taiwan lung cancer patients. Anticancer Res. 2011;31(10):3601-3605.
33.
AkkizHBayramSBekarAAkgöllüEÖzdilB. Cyclin D1 G870A polymorphism is associated with an increased risk of hepatocellular carcinoma in the Turkish population: case-control study. Cancer Epidemiol. 2010;34(3):298-302.
34.
GuptaVKFeberAXiLet al. Association between CCND1 G/A870 polymorphism, allele-specific amplification, cyclin D1 expression, and survival in esophageal and lung carcinoma. Clin Cancer Res. 2008;14(23):7804-7812.
35.
BetticherDCHeighwayJHasletonPSet al. Prognostic significance of CCND1 (cyclin D1) overexpression in primary resected non-small-cell lung cancer. Br J Cancer. 1996;73(3):294-300.
