Association of two genomic variants with HPV subtype-specific risk of
cervical cancer
Abstract
Problem: Human papillomavirus infection is integral to developing
invasive cervical cancer in the majority of patients. It is unclear how
genetic susceptibility to HPV infection directs cervical disease
development by affecting host immune response. In a recent genome-wide
association study, rs9357152 and rs4243652 have been associated with
seropositivity for HPV16 or HPV18, respectively. Methods: We investigate
whether the two HPV susceptibility variants show association with
subtype-specific cervical cancer in a genetic case-control study
(rs9357152: N controls=560, N
HPV16+cases= 334; rs4243652: N controls=
544, N HPV18+cases= 115). We further tested whether
rs9357152 modulates gene expression of any of 36 genes at the human
leukocyte antigen locus in 257 cervical tissues. Results: rs9357152 was
associated with invasive HPV16+ve cancer (OR 1.30, 95% CI 1.01-1.66, P=
0.04) whereas rs4243652 was associated with HPV18+ve adenocarcinomas
(OR=2.71, 95% CI=1.09-6.75, P= 0.03). rs9357152 was found to be an eQTL
for HLA-DRB1 in HPV positive tissues (p
ANOVA=0.0009), with the risk allele lowering mRNA
levels. Conclusions: HPV seropositivity variants at chromosome 6 and 14
modulate subtype-specific cervical cancer risk. rs9357152 may exert its
effect through regulating HLA-DRB1 in the presence of HPV.