title: A common gene variant in PLS3 predicts colon cancer recurrence in women.
abstract: Recent evidence suggests that PLS3 (T-Plastin), an important member of the actin filamentous network, significantly influences cell invasion and metastasis. Germline polymorphisms within the PLS3 gene may impact the gene's function, resulting in inter-individual differences in tumor recurrence capacity. In the present study, we investigated the association of germline polymorphisms in PLS3 to predict time to recurrence (TTR) in patients with stage II and III colon cancer. A total of 264 patients with histologically confirmed colon cancer were included in this retrospective study. Germline DNA was genotyped for rs871773 C>T, rs757124 C>G, rs1557770 G>T, rs6643869 G>A, and rs2522188 C>T in the PLS3 gene by 5'-exonuclease (TaqMan™) technology. As the PLS3 gene is located on the X chromosome, a gender-specific statistical analysis was performed. In univariate analysis, the minor allele of PLS3 rs871773 C>T was significantly associated with decreased TTR in women (hazard ratio (HR) = 5.02; 95 % confidence interval (CI) = 1.251-20.114; p = 0.023) and remained significantly associated in multivariate analysis (HR = 6.165; 95 % CI = 1.538-24.716; p = 0.010). Female patients carrying the C/T genotype in PLS3 rs871773 showed a median TTR of 69 months. In contrast, female patients with homozygous C/C had a median TTR of 112 months. There were no significant associations between PLS3 rs871773 C>T and TTR in male and between the other polymorphisms and TTR in male or female colon cancer patients. In conclusion, we identified a common gene variant in PLS3 as an independent prognostic marker in female patients with stage II and III colon cancer. Larger prospective trials are warranted to confirm these findings.
authors.affiliation: Division of Clinical Oncology, Department of Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Joanna
authors.initials: J
authors.lastname: Szkandera
authors.forename: Thomas
authors.initials: T
authors.lastname: Winder
authors.forename: Michael
authors.initials: M
authors.lastname: Stotz
authors.forename: Melanie
authors.initials: M
authors.lastname: Weissmueller
authors.forename: Tanja
authors.initials: T
authors.lastname: Langsenlehner
authors.forename: Martin
authors.initials: M
authors.lastname: Pichler
authors.forename: Hellmut
authors.initials: H
authors.lastname: Samonigg
authors.forename: Wilfried
authors.initials: W
authors.lastname: Renner
authors.forename: Armin
authors.initials: A
authors.lastname: Gerger
authors.forename: Gudrun
authors.initials: G
authors.lastname: Absenger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012189:Retrospective Studies; D012737:Sex Factors
chemical_list: D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; C026742:plastin
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