No evidence of the involvement of the Fas −670 promoter polymorphism in cervical cancer in situ

Abstract

Dear Sir,In a recent study in this journal of Chinese patients, Lai et al. 1 suggest that a single nucleotide polymorphism (SNP) at position Ϫ670 in the Fas receptor promoter is associated with development of cervical cancer, implying a possible effect of Fas-mediated apoptosis. We studied this candidate locus in 278 affected sib-pairs (ASPs) from Sweden with a diagnosis of cervical cancer by genotyping of the Fas SNP and calculation of maximum lod-score (MLS) values. The ASPs show no significant deviation from random genetic sharing for the Fas receptor SNP either using the entire set of sib-pairs or when the material is stratified on the basis of carrier status of the human leukocyte antigen (HLA) class II susceptibility DQB1*0602/ DRB1*1501 haplotype. We conclude that the SNP in the Fas promoter does not have a major impact on the susceptibility to cervical carcinoma in Swedish patients.Infection with oncogenic human papillomavirus (HPV) is a necessary cause of cervical cancer, but genetic susceptibility factors are likely to affect the risk of malignant progression. 2,3 Associations between the HLA class II DQB1*0602/DRB1*1501 haplotype and cervical cancer have been reported, 4 -9 and higher HPV16 titer has been found in carriers of this haplotype. 10 Members of the tumour necrosis factor receptor superfamily, such as the transmembrane receptor Fas (CD95/APO-1), have a key role in apoptosis. A SNP at position Ϫ670 in the Fas promoter 11 was recently found to be associated with development of cervical carcinogenesis in a cohort of Chinese cases. 1 The binding of the Fas ligand (FasL) to the cell surface death receptor Fas activates intracellular cascades that ultimately cause apoptotic death of the cell. 12 The Fas SNP may affect risk of development of squamous cell carcinoma (SCC) through the Fas-mediated activation induced cell death (AICD), which normally prevents uncontrolled activation of lymphocytes. 1,13 If the Fas Ϫ670 A allele increases the Fas-mediated AICD resulting in a reduction of the cytotoxic T-lymphocyte (CTL) response, this might contribute to a persistent HPV infection. Elimination of virus-specific CTLs through Fas-mediated apoptosis has been documented in rodent livers, and this might point to a similar mechanism for development of chronic infections in hepatocytes. 14 We used a material consisting of 278 ASPs derived from the Swedish population to reexamine the role of the Fas polymorphism in cervical cancer development. The ASPs were identified by cross-linking the Swedish Cancer Registry and the National Family Register (Statistics, Sweden). DNA was extracted from peripheral blood leukocytes using standard phenol chloroform procedures. Ethical approval for the study was obtained from the Research Ethics Committee of Uppsala University. For our present study, 576 individuals corresponding to 278 ASPs were used (Table I). In this material, 23 (4%) of the women were diagnosed with invasive cervical cancer and 553 (96%) were diagnosed with cervical cancer in situ.Restriction fragment lengt...

Genetic Susceptibility for Cervical Cancer in African Populations: What Are the Host Genetic Drivers?

“…In addition, Zoodsma et al (2005) showed a relationship between FasR 670A ‡G and increased risk of adenocarcinoma and not squamous cell carcinoma of the cervix. However, in another study conducted in Chinese women, as well as in Caucasian populations, there was no association between Fas SNPs and cervical cancer susceptibility (Chen et al, 2013;Du et al, 2013;Engelmark et al, 2004b;Pavlidou et al, 2016;Sun et al, 2005) resonating with the findings from African populations (Table 3).…”

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

“…Zoosdma et al (13) have demonstrated that Fas-670 polymorphism might be involved in the development of adenocarcinoma of the cervix but not in the development of squamous cell carcinoma. Engelmark et al (21), Sun et al (11) and Chatterjee et al (18) did not show a significant association of the FAS/FASL polymorphisms with cervical cancer. Qiu et al (29) indicated that significantly increased risks in FAS-1377 AA carriers were found in the breast cancer subgroup but not in the lung cancer subgroup.…”

“…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.…”

A polymorphism of C-to-T substitution at −31 IL1B is associated with the risk of advanced gastric adenocarcinoma in a Japanese population

“…However, the results of our case-control study did not support this hypothesis, presumably because not all gastric tumors express FAS as reported (positive cases up to 30% of gastric cancer) (Vollmers et al 1997;Osaki et al 2001). Based on previous epidemiological studies of the polymorphism, the positive and negative correlation between the polymorphism and a risk of cervical squamous cell carcinoma has been disregarded (Lai et al 2003;Engelmark et al 2004). Immunohistochemical analysis using pathological specimens would help to provide a biological explanation to resolve this discrepancy.…”