Association of HLA-DRB1, interleukin-6 and cyclin D1 polymorphisms with cervical cancer in the Swedish population--a candidate gene approach.

Full Abstract

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.

Author information

Author/s: Castro, Felipe A (FA); 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);

Affiliation: Division Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

Journal: International journal of cancer. Journal international du cancer (Int J Cancer), published in United States. (Language: eng)

Reference: 2009-Oct; vol 125 (issue 8) : pp 1851-8

Dates: Created 2009/08/26; Completed 2009/09/21;

PMID: 19585495, status: MEDLINE (last retrieval date: 9/21/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Interleukin-6 - genetics
Middle Aged
Papillomaviridae - genetics
Papillomavirus Infections - epidemiology; genetics; virology
Polymerase Chain Reaction
Polymorphism, Single Nucleotide - genetics
Risk Factors
Sweden - epidemiology
Uterine Cervical Neoplasms - epidemiology; genetics; virology
Young Adult

Associated Chemicals: CCND1 protein, human (0) ; HLA-DR Antigens (0) ; Interleukin-6 (0) ; HLA-DRB1 antigen (128338-86-3) ; Cyclin D1 (136601-57-5)

These are the highest related articles currently in the database: