XPD, APE1, and MUTYH polymorphisms increase head and neck cancer risk: effect of gene-gene and gene-environment interactions.
In the present study, we investigated the effect of the DNA repair gene polymorphisms XPD Asp312Asn (G>A), APE1 Asp148Glu (T>G), and MUTYH Tyr165Cys (G>A) on the risk for head and neck cancer (HNC) in association with tobacco use in a population of Northeast India. The study subjects comprised of 80 HNC patients and 92 healthy controls. Genotyping was performed using amplification refractory mutation system-PCR (ARMS-PCR) for XPD Asp312Asn (G>A) and PCR using confronting two-pair primers (PCR-CTPP) for APE1 Asp148Glu (T>G) and MUTYH Tyr165Cys (G>A). The XPD Asp/Asn genotype increased the risk for HNC by 2-fold (odds ratio, OR = 2.072; 95 % CI, 1.025-4.190; p < 0.05). Interaction between APE1 Asp/Asp and XPD Asp/Asn as well as MUTYH Tyr/Tyr and XPD Asp/Asn genotypes further increased the risk by 2.9 (OR = 2.97; 95 % CI, 1.16-7.61; p < 0.05) and 2.3 (OR = 2.37; 95 % CI, 1.11-5.10; p < 0.05) folds, respectively. The risk was further increased in heavy smokers with the XPD Asp/Asn genotype and heavy tobacco chewers with XPD Asn/Asn genotype by 7.7-fold (OR = 7.749; 95 % CI, 2.53-23.70; p < 0.05) and 10-fold (OR = 10; 95 % CI, 1.26-79.13; p < 0.05), respectively. We thus conclude that the XPD Asp312Asn and APE1 Asp148Glu polymorphisms increase the risk for HNC in association with smoking and/or tobacco chewing in the population under study.
Department of Biotechnology, Assam University, Silchar, 788011, India.
Sambuddha
S
Das
Department of Biotechnology, Assam University, Silchar, 788011, India.
Aditi
A
Bhowmik
Department of ENT, Silchar Medical College and Hospital, Silchar, 788014, India.
Abhinandan
A
Bhattacharjee
Department of Biochemistry, Silchar Medical College and Hospital, Silchar, 788014, India.
Biswadeep
B
Choudhury
Department of Pathology, Silchar Medical College and Hospital, Silchar, 788014, India.
Momota
M
Naiding
Department of Biotechnology, Assam University, Silchar, 788011, India.
Agniv Kr
AK
Laskar
Department of Biotechnology, Assam University, Silchar, 788011, India.
Sankar Kumar
SK
Ghosh
Department of Biotechnology, Assam University, Silchar, 788011, India. yashminchoudhury@gmail.com.
Yashmin
Y
Choudhury
D000328:Adult; D016022:Case-Control Studies; D045647:DNA Glycosylases / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012306:Risk; D012307:Risk Factors; D012907:Smoking / Q000235:genetics; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
D045647:DNA Glycosylases; C061738:mutY adenine glycosylase; D051759:Xeroderma Pigmentosum Group D Protein; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; C497292:ERCC2 protein, human
APE1; Head and neck cancer; MUTYH; Polymorphism; XPD