Association of HLA-DRB1, interleukin-6 and cyclin D1 polymorphisms with cervical cancer in the Swedish population--a candidate gene approach.
High-risk human papillomavirus (hrHPV) infection is the major risk factor for cervical cancer (CxCa). The role of genetic susceptibility in the disease has been suggested, but the existing data lack consistency. We conducted a nested case-control study on 973 CxCa cases and 1,763 matched controls, from two Swedish population-based cohorts to examine the association of common genetic variants with CxCa risk. Human leukocyte antigen (HLA) alleles and 24 other polymorphisms in 14 genes were selected on the basis of reported association or mechanistic plausibility with an HPV infection or cervical cancer development. Genotyping was conducted using multiplex PCR and Luminex technology. A significant association of CxCa with various polymorphisms was observed: rs1800797 in the IL-6 gene (odds ratio [OR] = 0.88, 95% confidence intervals [CI]: 0.79-0.99); rs1041981 in the LTA gene (OR = 0.87, 95% CI: 0.78-0.98), and rs9344 in the CCND1 gene (OR = 1.14, 95% CI: 1.02-1.27), for those individuals carrying the rare allele. Additionally, the alleles 0401 and 1501 of the HLA class II DRB1 locus were associated with an increased risk (OR = 1.23, 95% CI: 1.04-1.45 and OR = 1.29, 95% CI: 1.11-1.50, respectively), and allele 1301 was associated with decreased risk (OR = 0.59, 95% CI: 0.47-0.73). The effects of CCND1 and the HLA*DRB1 alleles were independent of the effect of smoking. We did not find any association of risk with polymorphisms in genes related to the innate immune system. In conclusion, our study provides evidence for genetic susceptibility to CxCa due to variations in genes involved in the immune system and in cell cycle.
Castro
Felipe A
FA
Division Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.
Haimila
Katri
K
Sareneva
Inna
I
Schmitt
Markus
M
Lorenzo
Justo
J
Kunkel
Nelli
N
Kumar
Rajiv
R
Försti
Asta
A
Kjellberg
Lennart
L
Hallmans
Göran
G
Lehtinen
Matti
M
Hemminki
Kari
K
Pawlita
Michael
M
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002584:Cervix Uteri / Q000378:metabolism / Q000473:pathology; D019938:Cyclin D1 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D055815:Young Adult
C530104:CCND1 protein, human; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D015850:Interleukin-6; D019938:Cyclin D1