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http://dx.doi.org/10.7314/APJCP.2016.17.5.2491

Susceptible and Protective Associations of HLA Alleles and Haplotypes with Cervical Cancer in South India  

Rathika, Chinniah (Department of Immunology, School of Biological Sciences, Madurai Kamaraj University)
Murali, Vijayan (Department of Biotechnology and Genetic Engineering, Bharathidasan University)
Dhivakar, Mani (Department of Immunology, School of Biological Sciences, Madurai Kamaraj University)
Kamaraj, Raju (Department of Immunology, School of Biological Sciences, Madurai Kamaraj University)
Malini, Ravi Padma (Department of Immunology, School of Biological Sciences, Madurai Kamaraj University)
Ramgopal, Sivanadham (Department of Immunology, School of Biological Sciences, Madurai Kamaraj University)
Balakrishnan, Karuppiah (Department of Immunology, School of Biological Sciences, Madurai Kamaraj University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.17, no.5, 2016 , pp. 2491-2497 More about this Journal
Abstract
Background: Human leukocyte antigen (HLA) genes have been implicated in cervical cancer in several populations. Objectives: To study the predispositions of HLA alleles/haplotypes with cervical cancer. Materials and Methods: Clinically diagnosed and PAP smear confirmed cervical cancer patients (n 48) and age matched controls (n 47) were genotyped for HLA-A,-B,-DRB1* and DQB1* alleles by PCR-SSP methods. Results: The frequencies of alleles DRB1*04 (OR=2.57), DRB1*15 (OR=2.04), DQB1*0301 (OR=4.91), DQB1*0601 (OR=2.21), B*15 (OR=13.03) and B*07 (OR=6.23) were higher in cervical cancer patients than in the controls. The frequencies of alleles DRB1*10 (OR=0.22) and B*35 (OR=0.19) were decreased. Strong disease associations were observed for haplotypes DRB1*15-DQB1*0601 (OR=6.56; p< $3.5{\times}10^{-4}$), DRB1*14-DQB1*0501 (OR=6.51; p<0.039) and A*11-B*07 (OR=3.95; p<0.005). The reduced frequencies of haplotypes DRB1*10-DQB1*0501 (OR=0.45), A*03-B*35 (OR=0.25) and A*11-B*35 (OR= 0.06) among patients suggested a protective association. HLA-C* typing of 8 patients who possessed a unique three locus haplotype 'A*11-B*07-DRB1*04' (8/48; 16.66%; OR=6.51; p<0.039) revealed the presence of a four locus haplotype 'A*11-B*07-C*01-DRB1*04' in patients (4/8; 50%). Amino acid variation analysis of susceptible allele DQB1*0601 suggested 'tyrosine' at positions ${\beta}9$ and ${\beta}37$ and tyrosine-non-tyrosine genotype combination increased the risk of cervical cancer. Conclusions: Strong susceptible associations were documented for HLA alleles B*15, B*07, DRB1*04, DRB1*15, DQB1*0301, DQB1*0601 and haplotypes DRB1*15-DQB1*0601 and DRB1*14-DQB1*0501. Further, protective associations were evidenced for alleles B*35 and DRB1*10 and haplotypes A*11-B*35 and DRB1*10-DQB1*0501 with cervical cancer in South India.
Keywords
Human leukocyte antigen; alleles/haplotypes; cervical cancer; susceptibility; protection; South India;
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