Analysis of the entire HLA region in susceptibility for cervical cancer: a comprehensive study

Zoodsma, Margreet; Nolte, Ilja M.; Schipper, Martijn; Oosterom, Elvira; Steege, Gerrit van der; Vries, de Elisabeth G. E.; Meerman, te Gerhardus; Zee, van der Ate

doi:10.1136/jmg.2005.031351

Cited by 39 publications

(27 citation statements)

References 47 publications

(12 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, we cannot exclude the contribution of other HLA or non-HLA genes such as TNFalpha, 19 TAP2 42, 43 or MICA 43 that may be in linkage disequilibrium with the genetic markers tested. It has also been demonstrated that at least 36 HLA allele combinations are associated with a susceptibility to CxCa in the US Caucasian population.…”

Section: Discussionmentioning

confidence: 96%

Association of HLA‐DRB1, interleukin‐6 and cyclin D1 polymorphisms with cervical cancer in the Swedish population—A candidate gene approach

Castro

Haimila

Sareneva

et al. 2009

Intl Journal of Cancer

View full text Add to dashboard Cite

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] 5 0.88, 95% confidence intervals [CI]: 0.79-0.99); rs1041981 in the LTA gene (OR 5 0.87, 95% CI: 0.78-0.98), and rs9344 in the CCND1 gene (OR 5 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 5 1.23, 95% CI: 1.04-1.45 and OR 5 1.29, 95% CI: 1.11-1.50, respectively), and allele 1301 was associated with decreased risk (OR 5 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. ' UICCKey words: nested case-control study; genetic study; host factors; polymorphisms; human papillomavirus; HPV Cervical cancer (CxCa) is the second most common cancer in women worldwide. It accounts for 250,000 deaths per year and at least 80% of them occur in developing countries.

show abstract

Section: Discussionmentioning

confidence: 96%

Association of HLA‐DRB1, interleukin‐6 and cyclin D1 polymorphisms with cervical cancer in the Swedish population—A candidate gene approach

Castro

Haimila

Sareneva

et al. 2009

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…Zoodsma et al (19), in a study conducted in the Netherlands, used microsatellite markers and two single nucleotide polymorphisms on 6p21 and found two markers (one near the HLA-DQ and HLA-DR genes and the other in MICA) that were strongly associated with risk of cervical cancer. Engelmark et al (20) used an affected sib-pair approach in a Swedish study that performed typing of the five class I and class II loci, and reported a strong effect of class II but not class I loci in *ORs are adjusted for race.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 Loci and Squamous Cell Cervical Cancer Risk

Madeleine¹,

Johnson²,

Smith

et al. 2008

Cancer Research

114

View full text Add to dashboard Cite

Variation in human major histocompatibility genes may influence the risk of squamous cell cervical cancer (SCC) by altering the efficiency of the T-cell-mediated immune response to human papillomavirus (HPV) antigens. We used high-resolution methods to genotype human leukocyte antigen (HLA) class I (A, B, and Cw) and class II (DRB1 and DQB1) loci in 544 women with SCC and 542 controls. Recognizing that HLA molecules are codominantly expressed, we focused on co-occurring alleles. Among 137 allele combinations present at >5% in the case or control groups, 36 were significantly associated with SCC risk. All but one of the 30 combinations that increased risk included DQB1*0301, and 23 included subsets of A*0201-B*4402-Cw*0501-DRB1*0401-DQB1*0301. Another combination, B*4402-DRB1*1101-DQB1*0301, conferred a strong risk of SCC (odds ratio, 10.0; 95% confidence interval, 3.0-33.3). Among the six combinations that conferred a decreased risk of SCC, four included Cw*0701 or DQB1*02. Most multilocus results were similar for SCC that contained HPV16; a notable exception was A*0101-B*0801-Cw*0701-DRB1*0301-DQB1*0201 and its subsets, which were associated with HPV16-positive SCC (odds ratio, 0.5; 95% confidence interval, 0.3-0.9). The main multilocus associations were replicated in studies of cervical adenocarcinoma and vulvar cancer. These data confirm that T helper and cytotoxic T-cell responses are both important cofactors with HPV in cervical cancer etiology and indicate that cooccurring HLA alleles across loci seem to be more important than individual alleles. Thus, certain co-occurring alleles may be markers of disease risk that have clinical value as biomarkers for targeted screening or development of new therapies. [Cancer Res 2008;68(9):3532-9]

show abstract

“…Several reasons also may be responsible for the conflicting results about the association between HLA genes and HPV-associated cervical disease. Furthermore, other genes located in the HLA region and closely linked to HLA genes also may participate in the genetic susceptibility to HPV infection and cervical cancer [49]; for example, an association was found for MICA (allele 184) with cervical cancer (OR ϭ 1.31; 95% CI, 1.13-1.53). Analysis of the variability of tumor necrosis factor (TNF)-a microsatellites revealed that the TNFa11 and HLA-DQ6 alleles have a synergistic effect on the risk for SILs [50].…”

Section: Discussionmentioning

confidence: 99%

Human Leukocyte Antigen Class II Alleles and Risk of Cervical Cancer in China

Liu

Lin

et al. 2007

Human Immunology

View full text Add to dashboard Cite

Analysis of the entire HLA region in susceptibility for cervical cancer: a comprehensive study

Cited by 39 publications

References 47 publications

Association of HLA‐DRB1, interleukin‐6 and cyclin D1 polymorphisms with cervical cancer in the Swedish population—A candidate gene approach

Association of HLA‐DRB1, interleukin‐6 and cyclin D1 polymorphisms with cervical cancer in the Swedish population—A candidate gene approach

Comprehensive Analysis of HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 Loci and Squamous Cell Cervical Cancer Risk

Human Leukocyte Antigen Class II Alleles and Risk of Cervical Cancer in China

Contact Info

Product

Resources

About