| 1. |
- Ivansson, Emma L., et al.
(författare)
-
Interaction of immunological genes on chromosome 2q33 and IFNG in susceptibility to cervical cancer
- 2010
-
Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 116:3, s. 544-548
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Cervical cancer is caused by persistent infection with human papillomavirus and genetic susceptibility factors may augment disease risk. The immune response consists of complex interactions and it was recently proposed that the association of combinations of genotypes at several genes should be examined. In support of this the combination CD28+17(TT)/IFNG+874(AA) was shown to increase cervical cancer risk in a Brazilian population (VB Guzman et al. New approach reveals CD28 and IFNG gene interaction in the susceptibility to cervical cancer. Hum Mol Genet 2008;17:1838-44) and our aim was to replicate this finding. METHODS: We re-examined the proposed associations by analysis of polymorphisms at CD28, IFNG, TNF, PDCD1, ICOS and CTLA4 in 1306 Swedish cases and 811 controls. RESULTS: Logistic regression analysis detected association at single SNP level for CD28+17 (p=0.01), IFNG+874 (p=0.02), and PDCD1+7785 (p=0.04). The two locus combination CD28+17(TT)/IFNG+874(AA) (OR=0.76 (0.60-0.96, empirical p=0.03) and the three-locus combination CD28+17(TT)/IFNG+874(AA)/ICOS+1564(TT) (OR=0.65(0.49-0.87), empirical p=0.006) were associated with decreased risk. The strongest association was detected for the combination CTLA4-319 (CC)/IFNG (AA) (OR=0.67(0.53-0.84), empirical p=0.0007). CONCLUSION: The observation that these combinations of loci are associated in different populations supports their importance in cervical cancer development although the opposite directions of the effect call for clarification. The polymorphisms studied might not be the functional variants per se, but linked to those exerting a functional effect. The opposite associations in the two populations could then be explained by differences in linkage disequilibrium and population structure.
|
|
| 2. |
- Juko-Pecirep, Ivana, et al.
(författare)
-
Evaluation of Fanconi anaemia genes FANCA, FANCC and FANCL in cervical cancer susceptibility
- 2011
-
Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 122:2, s. 377-381
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. Disrupting the function of any of the 13 Fanconi anaemia (FA) genes causes a DNA repair deficiency disorder, with patients being susceptible to a number of cancer types. Variation in the family of FA genes has been suggested to affect risk of cervical cancer. The current study evaluates the influence of three genes in the FA pathway on cervical cancer risk in Swedish women. Methods. TagSNPs in FANCA, FANCC and FANCL were selected using the Tagger algorithm in Haploview. A total of 81 tagSNPs were genotyped in 782 cases (CIN3 or ICC) and 775 controls using the Illumina GoldenGate Assay and statistically analyzed for association with cervical cancer. Results. 72 SNPs were successfully genotyped in >98% of the samples. Nominal associations were detected for FANCA rs11649196 (p = 0.05) and rs4128763 in FANCC (p = 0.02). The associations did not withstand correction for multiple testing. Conclusions. The current study does not support that genetic variation in FANCA, FANCC or FANCL genes affects susceptibility to cervical cancer in the Swedish population.
|
|
