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.


OBJECTIVE
To study the predispositions of HLA alleles/haplotypes with cervical cancer.


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; < 3.5.10-4), DRB1*14-DQB1*0501 (OR=6.51; <0.039) and A*11-B*07 (OR=3.95; <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; <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 β9 and β37 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.
Department of Immunology, School of Biological Sciences, Madurai Kamaraj University, Madurai, India E-mail : immunobala@ mkuniversity.org.
Chinniah
C
Rathika
Vijayan
V
Murali
Mani
M
Dhivakar
Raju
R
Kamaraj
Ravi Padma
RP
Malini
Sivanadham
S
Ramgopal
Karuppiah
K
Balakrishnan
D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015236:HLA-C Antigens / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007194:India / Q000453:epidemiology; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D015995:Prevalence; D011379:Prognosis; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000517:prevention & control
D015236:HLA-C Antigens