Prognostic Impact of Different Gleason Patterns on Biopsy Within Grade Group 4 Prostate Cancer

Abstract Background Grade group (GG) 4 prostate cancer (PC) is considered a single entity; however, there are questions regarding prognostic heterogeneity. This study assessed the prognostic differences among various Gleason scores (GSs) classified as GG 4 PC on biopsy before radical prostatectomy (RP). Methods We conducted a multicenter retrospective study, and a total of 1791 patients (GS 3 + 5: 190; GS 4 + 4: 1557; and GS 5 + 3: 44) with biopsy GG 4 were included for analysis. Biochemical recurrence (BCR)-free survival, cancer-specific survival, and overall survival were analyzed using the Kaplan–Meier method and the log-rank test. Logistic regression analysis was performed to identify factors associated with high-risk surgical pathologic features. Cox regression models were used to analyze time-dependent oncologic endpoints. Results Over a median follow-up of 75 months, 750 patients (41.9%) experienced BCR, 146 (8.2%) died of any causes, and 57 (3.2%) died of PC. Biopsy GS 5 + 3 was associated with significantly higher rates of GS upgrading in RP specimens than GS 3 + 5 and GS 4 + 4. On multivariable analysis adjusted for clinicopathologic features, different GSs within GG 4 were significantly associated with BCR (p = 0.03) but not PC-specific or all-cause mortality. Study limitations include the lack of central pathological specimen evaluation. Conclusions Patients with GG 4 at biopsy exhibited some limited biological and clinical heterogeneity. Specifically, GS 5 + 3 had an increased risk of GS upgrading. This can help individualize patients’ counseling and encourage further study to refine biopsy specimen-based GG classification.

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Differential impact of tumor suppressor gene (TP53, PTEN, RB1) alterations and treatment outcomes in metastatic, hormone-sensitive prostate cancer

Prostate Cancer and Prostatic Diseases ◽

10.1038/s41391-021-00430-4 ◽

2021 ◽

Author(s):

Miguel Gonzalez Velez ◽

Heidi E. Kosiorek ◽

Jan B. Egan ◽

Andrea L. McNatty ◽

Irbaz B. Riaz ◽

...

Keyword(s):

Prostate Cancer ◽

Tumor Suppressor ◽

Cox Regression ◽

Multivariable Analysis ◽

Rank Test ◽

Prognostic Impact ◽

Line Treatment ◽

First Line ◽

Hormone Sensitive ◽

First Line Treatment

Abstract Background Altered tumor suppressor genes (TSG-alt) in prostate cancer are associated with worse outcomes. The prognostic value of TSG-alt in metastatic, hormone-sensitive prostate cancer (M1-HSPC) is unknown. We evaluated the effects of TSG-alt on outcomes in M1-HSPC and their prognostic impact by first-line treatment. Methods We retrospectively identified patients with M1-HSPC at our institution treated with first-line androgen deprivation therapy plus docetaxel (ADT + D) or abiraterone acetate (ADT + A). TSG-alt was defined as any alteration in one or more TSG. The main outcomes were Kaplan–Meier-estimated progression-free survival (PFS) and overall survival, analyzed with the log-rank test. Clinical characteristics were compared with the χ2 test and Kruskal–Wallis rank sum test. Cox regression was used for univariate and multivariable analyses. Results We identified 97 patients with M1-HSPC: 48 (49%) with ADT + A and 49 (51%) with ADT + D. Of 96 patients with data available, 33 (34%) had 1 TSG-alt, 16 (17%) had 2 TSG-alt, and 2 (2%) had 3 TSG-alt. The most common alterations were in TP53 (36%) and PTEN (31%); 6% had RB1 alterations. Median PFS was 13.1 (95% CI, 10.3–26.0) months for patients with normal TSGs (TSG-normal) vs. 7.8 (95% CI, 5.8–10.5) months for TSG-alt (P = 0.005). Median PFS was lower for patients with TSG-alt vs TSG-normal for those with ADT + A (TSG-alt: 8.0 [95% CI, 5.8–13.8] months vs. TSG-normal: 23.2 [95% CI, 13.1–not estimated] months), but not with ADT + D (TSG-alt: 7.8 [95% CI, 5.7–12.9] months vs. TSG-normal: 9.5 [95% CI, 4.8–24.7] months). On multivariable analysis, only TSG-alt predicted worse PFS (hazard ratio, 2.37; 95% CI, 1.42–3.96; P < 0.001). Conclusions The presence of TSG-alt outperforms clinical criteria for predicting early progression during first-line treatment of M1-HSPC. ADT + A was less effective in patients with than without TSG-alt. Confirmation of these findings may establish the need for inclusion of molecular stratification in treatment algorithms.

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Elevated Expression of Glycerol-3-Phosphate Phosphatase as a Biomarker of Poor Prognosis and Aggressive Prostate Cancer

Cancers ◽

10.3390/cancers13061273 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1273

Author(s):

Mohamed Amine Lounis ◽

Veronique Ouellet ◽

Benjamin Péant ◽

Christine Caron ◽

Zhenhong Li ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Metastasis ◽

Biochemical Recurrence ◽

Poor Prognosis ◽

Cox Regression ◽

Specific Antigen ◽

Metabolic Stress ◽

Cancer Specific Survival ◽

High Risk Prostate Cancer ◽

Increased Risk

The limitations of the biomarker prostate-specific antigen (PSA) necessitate the pursuit of biomarkers capable of better identifying high-risk prostate cancer (PC) patients in order to improve their therapeutic management and outcomes. Aggressive prostate tumors characteristically exhibit high rates of glycolysis and lipogenesis. Glycerol 3-phosphate phosphatase (G3PP), also known as phosphoglycolate phosphatase (PGP), is a recently identified mammalian enzyme, shown to play a role in the regulation of glucose metabolism, lipogenesis, lipolysis, and cellular nutrient-excess detoxification. We hypothesized that G3PP may relieve metabolic stress in cancer cells and assessed the association of its expression with PC patient prognosis. Using immunohistochemical staining, we assessed the epithelial expression of G3PP in two different radical prostatectomy (RP) cohorts with a total of 1797 patients, for whom information on biochemical recurrence (BCR), metastasis, and mortality was available. The association between biomarker expression, biochemical recurrence (BCR), bone metastasis, and prostate cancer-specific survival was established using log-rank and multivariable Cox regression analyses. High expression of G3PP in PC epithelial cells is associated with an increased risk of BCR, bone metastasis, and PC-specific mortality. Multivariate analysis revealed high G3PP expression in tumors as an independent predictor of BCR and bone metastasis development. High G3PP expression in tumors from patients eligible for prostatectomies is a new and independent prognostic biomarker of poor prognosis and aggressive PC for recurrence, bone metastasis, and mortality.

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Risk and Prognosis of Subsequent Primary Gastric Cancer

Oncology Research and Treatment ◽

10.1159/000521846 ◽

2022 ◽

Author(s):

Rongrong Wei ◽

Xinyu Du ◽

Jing Wang ◽

Qi Wang ◽

Xiaojie Zhu ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Survivors ◽

Cox Regression ◽

Prognostic Impact ◽

Cancer Specific Survival ◽

Cancer History ◽

Primary Gastric Cancer ◽

Actual Observation ◽

Increased Risk

Introduction: The incidence and prognostic impact of subsequent primary gastric cancer (GC) in a population of other cancer survivors is unclear. We aimed to evaluate susceptibility to subsequent primary GC in cancer survivors and prognosis of GC with prior cancer history. Methods: 2,211 and 23,416 GC cases with and without prior cancer history were retrospectively selected from the Surveillance, Epidemiology and End Results (SEER) database. Potential risk of developing subsequent primary GC was assessed through standardized incidence ratios (SIRs). Cox regression were adopted to analyze the influence of prior cancer history and clinical characteristic factors on the prognosis of subsequent primary GC. A nomogram was established to predict overall survival (OS). Propensity score matching (PSM) was conducted to eliminate possible bias. Results: Compared with general population, cancer survivors had an increased risk of subsequent primary GC (SIR 1.17, 95% CI 1.15-1.20, P<0.05). Prior cancer history was related to poor OS of GC [adjusted hazard ratio (aHR) 1.12, 95% CI 1.06-1.19, P<0.001], but not cancer-specific survival (aHR 0.97, 95% CI 0.89-1.05, P=0.441). In addition, age, grade, stage, year of diagnosis, surgery, TNM stage and tumor size were independent prognostic factors for OS in GC cases with prior cancers. The concordance index of the nomogram was 0.72 (95% CI 0.71-0.74), and calibrate curves showed good agreement between prediction by the nomogram and actual observation. Conclusions: Cancer survivors with increased risk of developing subsequent primary GC should strengthen their monitoring and follow-up to prevent occurrence of subsequent primary gastric cancer.

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Prognostic impact of CDKN2A/B deletion, TERT mutation, and EGFR amplification on histological and molecular IDH-wildtype glioblastoma

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa126 ◽

2020 ◽

Vol 2 (1) ◽

Author(s):

Sirui Ma ◽

Soumon Rudra ◽

Jian L Campian ◽

Sonika Dahiya ◽

Gavin P Dunn ◽

...

Keyword(s):

Cox Regression ◽

Multivariable Analysis ◽

Progression Free Survival ◽

Prognostic Impact ◽

Egfr Amplification ◽

Molecular Alterations ◽

Kaplan Meier ◽

P 16 ◽

Grade Ii ◽

Tert Mutation

Abstract Background We aimed to evaluate the clinical outcomes of molecular glioblastoma (mGBM) as compared to histological GBM (hGBM) and to determine the prognostic impact of TERT mutation, EGFR amplification, and CDKN2A/B deletion on isocitrate dehydrogenase (IDH)-wildtype GBM. Methods IDH-wildtype GBM patients treated with radiation therapy (RT) between 2012 and 2019 were retrospectively analyzed. mGBM was defined as grade II-III IDH-wildtype astrocytoma without histological features of GBM but with one of the following molecular alterations: TERT mutation, EGFR amplification, or combination of whole chromosome 7 gain and whole chromosome 10 loss. Overall survival (OS) and progression-free survival (PFS) were calculated from RT and analyzed using the Kaplan–Meier method. Multivariable analysis (MVA) was performed using Cox regression to identify independent predictors of OS and PFS. Results Of the 367 eligible patients, the median follow-up was 11.7 months. mGBM and hGBM did not have significantly different OS (median: 16.6 vs 13.5 months, respectively, P = .16), nor PFS (median: 11.7 vs 7.3 months, respectively, P = .08). However, mGBM was associated with better OS (hazard ratio [HR] 0.50, 95% CI 0.29–0.88) and PFS (HR 0.43, 95% CI 0.26–0.72) than hGBM after adjusting for known prognostic factors on MVA. CDKN2A/B deletion was associated with worse OS (HR 1.57, 95% CI 1.003–2.46) and PFS (HR 1.57, 95% CI 1.04–2.36) on MVA, but TERT mutation and EGFR amplification were not. Conclusion Criteria for mGBM may require further refinement and validation. CDKN2A/B deletion, but not TERT mutation or EGFR amplification, may be an independent prognostic biomarker for IDH-wildtype GBM patients.

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Optimal timing of post-prostatectomy radiotherapy for prostate cancer with high-risk pathologic features: A multi-institutional analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.24 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 24-24

Author(s):

William L. Hwang ◽

Rahul D. Tendulkar ◽

Andrzej Niemierko ◽

Shree Agrawal ◽

Kevin L. Stephans ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Locally Advanced ◽

Distant Metastases ◽

Recurrence Risk ◽

Optimal Timing ◽

Cancer Specific Survival ◽

Prognostic Features ◽

Kaplan Meier ◽

Pathologic Features

24 Background: The use of radical prostatectomy (RP) as initial treatment of high-risk/locally-advanced prostate cancer is increasing but patients (pts) with adverse pathologic features such as positive surgical margins or T3 disease have up to 70% recurrence risk. These high-risk pts may be managed with adjuvant radiotherapy (ART) or early salvage radiotherapy (ESRT). The optimal timing of post-operative radiotherapy is unclear. Methods: Individual data from 1566 consecutive pts with pT2N0M0/R1 or pT3N0M0/R0-1 disease who underwent post-prostatectomy ART or ESRT (1987-2013) at 10 academic centers were pooled. Post-irradiation freedom from biochemical failure (FFBF), freedom from distant metastases (FFDM), prostate-cancer specific survival (PCSS), and overall survival (OS) were compared using Kaplan-Meier and multivariate competing-risks regression (MVA) analyses. Propensity score (PS) matching was used to account for covariates potentially associated with treatment allocation. All outcomes were measured from the date of surgery to address lead time bias. Results: After PS-matching, median follow-up after surgery was 66 vs. 73 months for the ART and ESRT groups, respectively, and baseline characteristics were well-matched. ART was associated with higher FFBF (12-yr: 69% vs. 43%; log-rank P < 0.0001), FFDM (12-yr: 95% vs. 85%; log-rank P = 0.03), PCSS (12-yr: 99% vs. 94%; log-rank P = 0.048), and OS (12-yr: 91% vs. 79%; log-rank P = 0.01). ART, lower Gleason score, lower T-stage, nodal irradiation, and postoperative androgen deprivation therapy were favorable prognostic features on MVA for BF. Sensitivity analysis demonstrated that the decreased risk of BF associated with ART remained significant unless more than 56% of ART pts were cured by surgery alone. This threshold is greater than the estimated 12-yr FFBF of 46% after RP alone as determined by a contemporary nomogram. Conclusions: To the best of our knowledge, this represents the largest multi-institutional study to date comparing ART to ESRT. ART was associated with reduced biochemical recurrence, distant metastases, and death compared to ESRT for high-risk pts, pending prospective validation.

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Histopathological and Genomic Grading Provide Complementary Prognostic Information in Breast Cancer: A Study on Publicly Available Datasets

Pathology Research International ◽

10.4061/2011/890938 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Nilotpal Chowdhury

Keyword(s):

Breast Cancer ◽

Cox Regression ◽

Prognostic Indicator ◽

Rank Test ◽

Prognostic Impact ◽

Prognostic Information ◽

Free Survival ◽

Kaplan Meier ◽

Hazard Ratios ◽

Significant Prognostic Indicator

The genomic grade (GG) for breast cancer is thought to be the genomic counterpart of histopathological grade (HG). The motivation behind this study was to see whether HG retains its prognostic impact even when adjusted for GG, or whether it can be replaced by the latter. Four publicly available gene expression datasets were analyzed. Kaplan-Meier curves, log rank test, and Cox regression were used to study recurrence-free survival (RFS) and distant metastasis-free survival (DMFS). HG remained a significant prognostic indicator in low GG tumors (P = 0.003 for DMFS, P< 0.001 for RFS) but not in high GG tumors. HG grade 2 tumors differed significantly from HG grade 1 tumors, underlining the prognostic role of intermediate HG tumors. Additionally, GG could stratify HG 1 as well as HG 2 tumors into distinct prognostic groups. HG and GG add independent prognostic information to each other. However, the prognostic effects of both HG and GG are time varying, with the hazard ratios of high HG and GG tumors being markedly attenuated over time.

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Prognostic impact of sarcopenia in patients with metastatic hormone-sensitive prostate cancer

Japanese Journal of Clinical Oncology ◽

10.1093/jjco/hyaa045 ◽

2020 ◽

Vol 50 (8) ◽

pp. 933-939

Author(s):

Takashi Ikeda ◽

Hiroki Ishihara ◽

Junpei Iizuka ◽

Yasunobu Hashimoto ◽

Kazuhiko Yoshida ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Hazard Ratio ◽

Rank Test ◽

Prognostic Impact ◽

Castration Resistance ◽

Consensus Definition ◽

Cancer Specific Survival ◽

Free Survival ◽

Hormone Sensitive

Abstract Background Cancer cachexia is associated with a poor prognosis. This study aimed to investigate the association between sarcopenia and survival in patients with metastatic hormone-sensitive prostate cancer. Methods We retrospectively evaluated 197 patients diagnosed with metastatic hormone-sensitive prostate cancer in our department and its affiliated institution between January 2008 and December 2015. Sarcopenia was diagnosed according to the sex-specific consensus definition. Castration-resistance prostate cancer-free survival, cancer-specific survival and overall survival from the metastatic hormone-sensitive prostate cancer diagnoses were calculated using the Kaplan–Meier method and compared using the log-rank test. Risk factors affecting the survival outcomes were analyzed using the Cox proportional regression analysis. Results In total, 163 patients (82.7%) had sarcopenia. Cancer-specific survival and overall survival were significantly shorter in sarcopenic patients than in non-sarcopenic patients (median cancer-specific survival: 77.0 months vs. not reached, P = 0.0099; overall survival: 72.0 months vs. not reached, P = 0.0465), whereas castration-resistance prostate cancer-free survival did not significantly differ between the groups (P = 0.6063). Multivariate analyses showed that sarcopenia was an independent factor for cancer-specific survival (hazard ratio: 2.18, P = 0.0451), together with the Gleason score (hazard ratio: 1.87, P = 0.0272) and LATITUDE risk classification (hazard ratio: 2.73, P = 0.0008). Moreover, the prognostic association of sarcopenia was remarkable in patients aged <73.0 years (cancer-specific survival: 82.0 months vs. not reached, P = 0.0027; overall survival: 72.0 months vs. not reached, P = 0.0078 in sarcopenic vs. non-sarcopenic patients), whereas the association was not significant in patients aged ≥73.0 years (cancer-specific survival: 76.0 and 75.0 months, respectively, P = 0.7879; overall survival: 67.0 and 52.0 months, respectively, P = 0.7263). Conclusion Sarcopenia was an independent risk factor of cancer-specific survival in patients with metastatic hormone-sensitive prostate cancer, especially in younger patients.

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Impact of homozygote variant of bleomycin hydrolase (BLMH) gene on survival after chemotherapy for testicular cancer (TC)

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.5022 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 5022-5022

Author(s):

E. C. de Haas ◽

N. Zwart ◽

C. Meijer ◽

H. M. Boezen ◽

G. van der Steege ◽

...

Keyword(s):

Overall Survival ◽

Cox Regression ◽

Patient Characteristics ◽

Cytotoxic Agents ◽

Rank Test ◽

Future Research ◽

Polymorphism Analysis ◽

Kaplan Meier ◽

Response To Chemotherapy ◽

Increased Risk

5022 Background: With bleomycin, etoposide and cisplatin, cure of disseminated TC exceeds 80%. Next to tumor characteristics, response to chemotherapy may be determined by polymorphisms of genes involved in metabolism or target pathways of cytotoxic drugs. We investigated whether the A1450G polymorphic site in the gene for BLMH, an enzyme that inactivates bleomycin, is associated with differences in survival. Methods: Data were collected on survival of non-seminomatous TC patients treated with bleomycin and platinum from 1977–2003. BLMH genotype was determined from genomic DNA by PCR + restriction fragment length polymorphism analysis. The 3 genotypes [AA (wild-type), AG (heterozygote variant) and GG (homozygote variant)] were compared for patient characteristics, prognostic factors and received chemotherapy (Mann-Whitney U or χ2 test) and survival (Kaplan-Meier + log-rank test and Cox regression). Results: Data on BLMH genotype and survival were available for 304/372 patients (82%) with median follow-up of 10 yrs (range 0–27). The 3 genotypes AA (n=140), AG (n=133) and GG (n=31) did not differ significantly with respect to age, IGCCC prognosis, creatinine clearance and received dose of bleomycin and platinum. Overall survival of the GG genotype (61%) was worse than the overall survival of AA and AG combined (83%) (p=0.004), due to worse TC related survival of GG (71%) compared to AA + AG (90%) (p=0.001). Homozygote variants (GG) had a significantly increased risk for TC related death (odds ratio (OR) = 4.97) compared to wildtypes (AA) ( table ). Conclusion: Germline presence of the homozygote variant (GG) of the BLMH gene appears to be an unfavorable prognostic factor for TC related death after chemotherapy, in addition to the commonly used IGCCC prognosis. It is unclear whether this is due to alterations in metabolism or target pathways of bleomycin or other cytotoxic agents, or linkage disequilibrium to a yet unknown involved gene. This needs to be unraveled in future research. [Table: see text] No significant financial relationships to disclose.

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Chemoradiation-related lymphopenia and its association with survival in patients with anal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.3 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 3-3

Author(s):

Grace Lee ◽

Daniel W. Kim ◽

Vinayak Muralidhar ◽

Devarati Mitra ◽

Nora Horick ◽

...

Keyword(s):

Cancer Patients ◽

Anal Cancer ◽

Cox Regression ◽

Cox Model ◽

Rank Test ◽

Anal Squamous Cell Carcinoma ◽

Cox Regression Analysis ◽

Risk Of Death ◽

Kaplan Meier ◽

Increased Risk

3 Background: While treatment-related lymphopenia (TRL) is common and associated with poorer survival in multiple solid malignancies, little data exists for anal cancer. We evaluated TRL and its association with survival in anal cancer patients treated with chemoradiation (CRT). Methods: A retrospective analysis of 140 patients with non-metastatic anal squamous cell carcinoma (SCC) treated with definitive CRT was performed. Total lymphocyte counts (TLC) at baseline and monthly intervals up to 12 months after initiating CRT were analyzed. Multivariable Cox regression analysis was performed to evaluate the association between overall survival (OS) and TRL, dichotomized by G4 TRL ( < 0.2k/μl) two months after initiating CRT. Kaplan-Meier and log-rank tests were used to compare OS between patients with versus without G4 TRL. Results: Median time of follow-up was 55 months. Prior to CRT, 95% of patients had a normal TLC ( > 1k/μl). Two months after initiating CRT, there was a median of 71% reduction in TLC from baseline and 84% of patients had TRL: 11% G1, 31% G2, 34% G3, and 8% G4. On multivariable Cox model, G4 TRL at two months was associated with a 3.7-fold increased risk of death (p = 0.013). On log-rank test, the 5-year OS rate was shorter in the cohort with versus without G4 TRL at two months (32% vs. 86%, p < 0.001). Conclusions: TRL is common and may be another prognostic marker of OS in anal cancer patients treated with CRT. The association between TRL and OS supports the hypothesis that host immunity plays an important role in survival among patients with anal cancer. These results support ongoing efforts of randomized trials underway to evaluate the potential role of immunotherapy in localized anal cancer.

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8-Oxoguanine DNA Glycosylase (OGG1) Cys326 Variant: Increased Risk for Worse Outcome of Patients with Locally Advanced Rectal Cancer after Multimodal Therapy

Cancers ◽

10.3390/cancers13112805 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2805

Author(s):

Martin Leu ◽

Theresa Riebeling ◽

Leif Hendrik Dröge ◽

Laura Hubert ◽

Manuel Guhlich ◽

...

Keyword(s):

Rectal Cancer ◽

Clinical Outcome ◽

Cox Regression ◽

Locally Advanced ◽

Multivariable Analysis ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Rank Test ◽

Neoadjuvant Radiochemotherapy ◽

Increased Risk

Despite excellent loco-regional control by multimodal treatment of locally advanced rectal cancer, a substantial portion of patients succumb to this disease. As many treatment effects are mediated via reactive oxygen species (ROS), we evaluated the effect of single nucleotide polymorphisms (SNPs) in ROS-related genes on clinical outcome. Based on the literature, eight SNPs in seven ROS-related genes were assayed. Eligible patients (n = 287) diagnosed with UICC stage II/III rectal cancer were treated multimodally starting with neoadjuvant radiochemotherapy (N-RCT) according to the clinical trial protocols of CAO/ARO/AIO-94, CAO/ARO/AIO-04, TransValid-A, and TransValid-B. The median follow-up was 64.4 months. The Ser326Cys polymorphism in the human OGG1 gene affected clinical outcome, in particular cancer-specific survival (CSS). This effect was comparable in extent to the ypN status, an already established strong prognosticator for patient outcome. Homozygous and heterozygous carriers of the Cys326 variant (n = 105) encountered a significantly worse CSS (p = 0.0004 according to the log-rank test, p = 0.01 upon multiple testing adjustment). Cox regression elicited a hazard ratio for CSS of 3.64 (95% confidence interval 1.70–7.78) for patients harboring the Cys326 allele. In a multivariable analysis, the effect of Cys326 on CSS was preserved. We propose the genetic polymorphism Ser326Cys as a promising biomarker for outcome in rectal cancer.

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