Identification of novel potential genetic predictors of urothelial bladder carcinoma susceptibility in Pakistani population

Abstract

Urothelial bladder carcinoma (UBC) is the most common among urinary bladder neoplasms. We carried out a preliminary study to determine the genetic etiology of UBC in Pakistani population, for this 25 sequence variants from 17 candidate genes were studied in 400 individuals by using polymerase chain reaction-based techniques. Multivariate logistic regression analysis was performed for association analysis of the overall data as well as the data stratified by smoking status, tumor grade and tumor stage. Variants of GSTM1, IGFBP3, LEPR and ACE were found to be associated with altered UBC risk in the overall comparison. CYP1B1 and CDKN1A variants displayed a risk modulation among smokers; IGFBP3 and LEPR variants among non-smokers while GSTM1 polymorphism exhibited association with both. GSTM1 and LEPR variants conferred an altered susceptibility to low grade UBC; GSTT1, IGFBP3 and PPARG variants to high grade UBC while ACE polymorphism to both grades. GSTM1 and LEPR variants exhibited risk modulation for non-muscle-invasive bladder cancer (NMIBC); GSTT1 and PPARG variants for muscle-invasive bladder cancer (MIBC), and ACE variant for NMIBC as well as MIBC. In general, the susceptibility markers were common for low grade and NMIBC; and distinct from those for high grade and MIBC indicating the distinct pathologies of both groups. In brief, our results conform to reports of previously associated variants in addition to identifying novel potential genetic predictors of UBC susceptibility.

Investigation ofleptin receptorrs1137101 G>A polymorphism with cancer risk: evidence from 35936 subjects

“…In total, 44 independent case–control studies with 35,936 subjects (13,711 cases and 22,225 controls) were included. Among them, 20 were Caucasians [15,16,20–23,34,36,37,39–43,45–48], 14 were Asians [9,11–14,17,24,26,33,44], 1 was African [38], and 9 were mixed populations [18,19,25,35]. Twenty-two case–control studies were designed as hospital-based investigation [9,11–14,17,18,21,22,24,26,33,34,38,44,46,48], seventeen studies were designed as population-based investigation [16,19,25,35–37,40,41,43,45,47], and the source of control in other five studies were unknown [15,20,23,39,42].…”

“…Among them, 20 were Caucasians [15,16,20–23,34,36,37,39–43,45–48], 14 were Asians [9,11–14,17,24,26,33,44], 1 was African [38], and 9 were mixed populations [18,19,25,35]. Twenty-two case–control studies were designed as hospital-based investigation [9,11–14,17,18,21,22,24,26,33,34,38,44,46,48], seventeen studies were designed as population-based investigation [16,19,25,35–37,40,41,43,45,47], and the source of control in other five studies were unknown [15,20,23,39,42]. Of all the eligible studies, 24 focused on breast cancer [12,14,15,19,20,22,33,35,36,38,41,42,44,47,48], 4 focused on esophageal cancer [13,40], 4 focused on colorectal cancer [34,37,39,46], 3 focused on hepatocellular carcinoma [9,11,26], 2 focused on non-Hodgkin’s lymphoma [43,45], 3 focused on oral and oropharyngeal cancer [18,21,25], 2 focused on renal cell carcinoma [17,24], and 2 focused on other cancers [16,23].…”

“…LEPR rs1137101 G>A polymorphism is located on the exon region of LEPR gene, and it has been thought to be involved in the development of cancer by a number of studies. Several case–control studies reported that LEPR rs1137101 G>A polymorphism might be associated with the decreased risk of cancer [16,22,26,41,42]. However, several primary studies also suggested that LEPR rs1137101 locus could promote the progression of cancers [15,18].…”

<p>Leptin rs7799039 (G2548A) polymorphism is associated with cancer risk: a meta-analysis involving 25,799 subjects</p>

“…Among them, 19 were conducted in Caucasians,26–44 eight performed in Asians,21,45–50,54 and four were in mixed populations 51–53. Nine were population-based,27,28,30,33,37,38,43,44,50 and 22 case–control were hospital-based studies 21,26,29,31,32,34–36,39–42,45–49,51–54. Of all the eligible studies, 11 focused on breast cancer,33,37–40,44,48,49,51,53 four focused on colorectal cancer (CRC),31,32,41,52 three focused on prostate cancer (PC),26,30,34 and 13 focused on other cancers 21,27–29,35,36,42,43,45–47,50,54.…”

Systematic Review: Genetic Associations for Prognostic Factors of Urinary Bladder Cancer

“…Low-grade UBC definitions were as follows: G1, 18,54,62,70 G2, 35,58,62,70 G1 + G2, 36 low-grade, 69,71 and G1 + G2 + papilloma. 32 High-grade UBC was usually defined as grade 3 UBC, 11,27,29,32,36,37,47,50,67,70,72-75 a combination of G2 and G3 NMIBC, 54,66 and some studies have reported estimates for grade 4 tumors, without a reference for the grading system used (G3 + G4 42 and G2 + G3 + G4) 33 (Supplementary Table 5).…”