Variants of chemokine receptor 2 and interleukin 4 receptor, but not interleukin 10 or Fas ligand, increase risk of cervical cancer

Abstract

Cervical cancer is caused by persistent infection of oncogenic human papillomavirus (HPV). Most infected women clear the virus without developing cervical lesions and it is likely that immunological host factors affect susceptibility to cervical cancer. The impact of the human leukocyte antigen (HLA) locus on the risk of cervical cancer is established and several other genes involved in immunological pathways have been suggested as biologically plausible candidates. The aim of this study was to examine the potential role of polymorphisms in 4 candidate genes by analysis of 1,306 familial cervical cancer cases and 288 controls. The following genes and polymorphisms were studied: Chemokine receptor 2 (CCR-2) V64I; Interleukin 4 receptor a (IL-4R) I75V, S503P and Q576R; Interleukin 10 (IL-10) 2592; and Fas ligand (FasL) 2844. The CCR-2 64I variant was associated with decreased risk of cervical cancer; homozygote carriers of the 64I variant had an odds ratio of 0.31 (0.12-0.77). This association was detected in both carriers and noncarriers of the HLA DQB1*0602 cervical cancer risk allele. The IL-4R 75V variant was associated with increased risk of cervical tumors, cases homozygote for 75V had an odds ratio of 1.91 (1.27-2.86) with a tendency that the association was stronger in noncarriers of the DQB1*0602 allele. We did not find any association for IL-10 2592, or FasL 2844, previously reported to be associated with cervical cancer in the Dutch and Chinese populations, respectively. ' 2007 Wiley-Liss, Inc.

Lack of association between the FAS/FASL polymorphisms and cervical cancer risk: A meta-analysis

“…Based on a literature search and selection, a total of 10 publications (11)(12)(13)(14)(15)(16)(17)(18)(19)22) comparing the FAS/ FASL polymorphism and cervical cancer susceptibility were identified. Among these studies, 1 study was in Chinese (22) and 1 study contained data on two different ethnicities (18).…”

“…Although evidence of an association between FAS/FASL polymorphisms and cervical cancer risk has been reported, the findings remain controversial (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Therefore, we performed a meta-analysis of all published studies on the association between the FAS/FASL polymorphisms and cervical cancer.…”

The paradox of IL-10-mediated modulation in cervical cancer

“…The genotype predisposing to the production of high levels of IL-10 is more commonly observed in cervical cancer patients, compared to healthy women (17). However, findings of a previous suggested that the variants of chemokine receptor 2 and IL-4 receptor, rather than IL-10 or Fas ligand, increase the risk of cervical cancer (18).…”

Pathway-based analysis of genetic susceptibility to cervical cancer in situ: HLA-DPB1 affects risk in Swedish women

“…This points to the importance of the immune response toward HPV infection in preventing carcinoma development and explains why genetic variations in genes of immunological pathways, in addition to the HLA class II genes, [6][7][8][9][10][11][12] are associated with in situ (2011) 12, 605 -614. and invasive cervical cancer. 9,[14][15][16][17][18] However, only a handful of the identified genes show a consistent effect in multiple cohorts, and thus additional risk factors for persistent infection and tumor development are likely to exist. Assuming that variation in genes with a specific function is of particular interest, there are several optional study designs.…”