PD1.5 variant on PDCD1 gene, regulator of T lymphocyte activity, influences non-muscle-invasive bladder cancer risk

Gabriela Vilas Bôas Gomez; Larissa Nara Alegrini Longhi; Helena Paes Almeida Saito; Gustavo Jacob Lourenço; Rodolfo Borges Dos Reis; Marcos Tobias Machado; Leonardo Oliveira Reis; Fernandes Denardi; Carmen Silvia Passos Lima

PD1.5 variant on PDCD1 gene, regulator of T lymphocyte activity, influences non-muscle-invasive bladder cancer risk

Am J Clin Exp Urol. 2022 Oct 15;10(5):334-340. eCollection 2022.

Affiliations

¹ Laboratory of Cancer Genetics, Faculty of Medical Sciences, University of Campinas Campinas, São Paulo, Brazil.
² Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto, University of São Paulo Ribeirão Preto, São Paulo, Brazil.
³ Department of Urooncology, Faculty of Medicine ABC Santo André, São Paulo, Brazil.
⁴ UroScience Faculty of Medical Sciences, University of Campinas Campinas, São Paulo, Brazil.
⁵ Life Sciences Center, Faculty of Medical Sciences, Pontifical Catholic University of Campinas Campinas, São Paulo, Brazil.
⁶ Department of Surgery, Faculty of Medical Sciences, University of Campinas Campinas, São Paulo, Brazil.
⁷ Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas Campinas, São Paulo, Brazil.

PMID: 36313211
PMCID: PMC9605939

Abstract

Background: Since failure in recognition of abnormal cells by the immune system has an important role in bladder cancer development and progression, this study aimed to evaluate whether PD1 (c.627+252C>T) and PD1.5 (c.804C>T) single-nucleotide variants (SNVs) in PDCD1 gene, enrolled in modulation of T lymphocyte activity, influence risk, clinicopathological aspects, and outcome of non-muscle-invasive bladder cancer (NMIBC) patients.

Material and methods: DNA genotyping by real-time polymerase chain reaction was offered to 160 non muscle invasive bladder cancer (NMIBC) patients and 250 controls. One hundred and twenty-seven patients treated with bladder transurethral resection and intravesical bacillus Calmette-Guérin were enrolled in survival analyses.

Results: Individuals with PD1.5 CC genotype had 2.3-fold increased risk of developing NMIBC. Similar genotype and haplotype frequencies were seen in patients stratified by clinicopathological aspects. Patients with T allele, CT or TT plus CT or TT genotype and TT haplotype of PD1 and PD1.5 SNVs had up to 4.0-times greater chances of presenting NMIBC relapse and death by any cause than the remaining patients, but analysis of NMIBC specific survival was not possible in study due to the small number of patients evolving to death during follow up.

Conclusions: Our data presented for the first time, preliminary evidence that inherited abnormality in regulation of T lymphocyte activity alters NMIBC risk.

Keywords: Bladder cancer; PDCD1 gene; prognosis; risk; single-nucleotide variant.