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

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 DRB104 (OR=2.57), DRB115 (OR=2.04), DQB10301 (OR=4.91), DQB10601 (OR=2.21), B15 (OR=13.03) and B07 (OR=6.23) were higher in cervical cancer patients than in the controls. The frequencies of alleles DRB110 (OR=0.22) and B35 (OR=0.19) were decreased. Strong disease associations were observed for haplotypes DRB115-DQB10601 (OR=6.56; < 3.5.10-4), DRB114-DQB10501 (OR=6.51; <0.039) and A11-B07 (OR=3.95; <0.005). The reduced frequencies of haplotypes DRB110-DQB10501 (OR=0.45), A03-B35 (OR=0.25) and A11-B35 (OR= 0.06) among patients suggested a protective association. HLA-C* typing of 8 patients who possessed a unique three locus haplotype 'A11-B07-DRB104' (8/48; 16.66%; OR=6.51; <0.039) revealed the presence of a four locus haplotype 'A11-B07-C01-DRB104' in patients (4/8; 50%). Amino acid variation analysis of susceptible allele DQB10601 suggested 'tyrosine' at positions β9 and β37 and tyrosine-non-tyrosine genotype combination increased the risk of cervical cancer.

CONCLUSIONS

Strong susceptible associations were documented for HLA alleles B15, B07, DRB104, DRB115, DQB10301, DQB10601 and haplotypes DRB115-DQB10601 and DRB114-DQB10501. Further, protective associations were evidenced for alleles B35 and DRB110 and haplotypes A11-B35 and DRB110-DQB10501 with cervical cancer in South India.