PDCD1, CTLA-4 and p53 Gene Polymorphism and Susceptibility to Gestational Trophoblastic Diseases
JOURNAL OF REPRODUCTIVE MEDICINE
Authors: Dehaghani, Alamtaj Samsami; Kashef, Mohammad Amin; Ghaemenia, Mehdi; Sarraf, Zahra; Khaghanzadeh, Narges; Fattahi, Mohammad Javad; Ghaderi, Abbas
Abstract
OBJECTIVE: Gestational trophoblastic neoplasms (also termed gestational trophoblastic diseases [GTDs]) encompass a spectrum of interrelated tumors originating from trophoblasts. The search is ongoing for identification of the culpable gene defects in GTDs. Considering the role of PDCD1, CTLA-4 and p53 genes in immune regulation and tumor progression, we explored the association of single-nucleotide polymorphisms (SNPs) corresponding to each gene and GTDs. STUDY DESIGN: In a genetic association study, PD1.5 (7785) C/T, CTLA-4 +49 A/G, and p53 codon 72 Arg/Pro SNPs were genotyped in case-control groups with patient/control ratios of 92:295, 83:84 and 85:150, respectively. RESULTS: The C/T genotype of the PDCD1 gene was significantly more prevalent among patients with GTDs (40.2%) than controls (19%) (odds ratio [OR]=2.87; 95% CI=1.72, 4.77; p < 0.001). Moreover, the C allele was present in 65.8%, of patients and 49.5% of controls (OR =1.96; 95% CI=1.38, 2.76; p < 0.001). There was no difference in the distribution of each genotype or allele between patients with GTDs and controls considering other studied SNPs. CONCLUSION: The results of the current study demonstrate that SNPs in the PDCD1 gene confer susceptibility to GTDs, while there is no association between CTLA-4 and p53 gene polymorphisms and GTDs in an Iranian population. (J Reprod Med 2009;54:25-31)
Genetic variations in immunomodulatory pathways to predict survival in patients with locoregional gastric cancer
PHARMACOGENOMICS JOURNAL
Authors: Sunakawa, Y.; Cao, S.; Volz, N. B.; Berger, M. D.; Yang, D.; Parekh, A.; Zhang, W.; Matsusaka, S.; Ning, Y.; Stremitzer, S.; Stintzing, S.; Sebio, A.; Okazaki, S.; Wakatsuki, T.; Azuma, M.; Watanabe, M.; Koizumi, W.; Wu, A. H.; Lenz, H-J
Abstract
Immunomodulator-targeting therapies are under development in gastric cancer (GC). However, the role of genes modulating antitumor immunity in GC remains poorly understood. We investigated the association of variations in genes involved in immunomodulatory pathways with overall survival (OS) in locoregional GC patients. Extracted genomic DNA was analyzed for 35 functional single-nucleotide polymorphisms in genes, PDCD1, CD274, CTLA4, FOXP3, LAG3, ADORA2A, NT5E and IDO1, in 162 Japanese patients as discovery set and 277 US patients as validation set. The C allele of PDCD1 rs10204525 had univariate and multivariable associations with shorter OS in Japanese cohort (P = 0.015, P = 0.043, respectively). In US cohort the C allele predicted worse OS (P = 0.007). Univariate and multivariable analyses revealed IDO1 rs9657182 associated with OS in the Japanese cohort; moreover, the association was confirmed in the US cohort. Genetic predisposition of the host in the immunomodulators may serve as a prognostic biomarker in patients with locoregional GC.