METHODS: We performed a genome-wide survival analysis of cause-specific death in 24,023 prostate cancer patients (3,513 disease-specific deaths) from the PRACTICAL and BPC3 consortia. Top findings were assessed for replication in a Norwegian cohort (CONOR).
RESULTS: We observed no significant association between genetic variants and prostate cancer survival.
CONCLUSIONS: Common genetic variants with large impact on prostate cancer survival were not observed in this study.
IMPACT: Future studies should be designed for identification of rare variants with large effect sizes or common variants with small effect sizes.
SIGNIFICANCE: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. Cancer Discov; 6(9); 1052-67. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 932.
METHODS: The case-control portion of the study was conducted in nine UK centers with men ages 50-69 years who underwent prostate-specific antigen screening for prostate cancer within the Prostate Testing for Cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium.
RESULTS: Thirty-five metabolites were strongly associated with prostate cancer (P < 0.0014, multiple-testing threshold). These fell into four classes: (i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); (ii) fatty acids and ratios; (iii) amino acids; (iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal.
CONCLUSIONS: We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk.
IMPACT: The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.
METHODS: We applied H. pylori multiplex serology to measure antibody responses to 13 H. pylori proteins in prediagnostic serum samples from 485 colorectal cancer cases and 485 matched controls nested within the EPIC study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable conditional logistic regression to estimate the association of H. pylori overall and protein-specific seropositivity with odds of developing colorectal cancer.
RESULTS: Fifty-one percent of colorectal cancer cases were H. pylori seropositive compared with 44% of controls, resulting in an OR of 1.36 (95% CI, 1.00-1.85). Among the 13 individual H. pylori proteins, the association was driven mostly by seropositivity to Helicobacter cysteine-rich protein C (HcpC; OR: 1.66; 95% CI, 1.19-2.30) and Vacuolating cytotoxin A (VacA) (OR: 1.34; 95% CI, 0.99-1.82), the latter being nonstatistically significant only in the fully adjusted model.
CONCLUSIONS: In this prospective multicenter European study, antibody responses to H. pylori proteins, specifically HcpC and VacA, were associated with an increased risk of developing colorectal cancer.
IMPACT: Biological mechanisms for a potential causal role of H. pylori in colorectal carcinogenesis need to be elucidated, and subsequently whether H. pylori eradication may decrease colorectal cancer incidence.
HYPOTHESIS: Medial MAT would improve anteroposterior stability, and lateral MAT would improve rotational stability.
STUDY DESIGN: Cohort study; Level of evidence, 3.
METHOD: We retrospectively investigated 31 cases of MAT after a previous total or nearly total meniscectomy and ACL reconstruction between November 2008 and June 2017. Cases were divided into medial (16 cases) and lateral (15 cases) MAT groups. The patients were assessed preoperatively and at the 2-year follow-up.
RESULTS: In the medial MAT group, the International Knee Documentation Committee, Lysholm, Lysholm instability, and Tegner scores improved significantly at the 2-year follow-up, and there were also significant improvements in the anterior drawer, Lachman, and pivot-shift tests. In the lateral MAT group, the Lysholm and Tegner scores improved significantly at the 2-year follow-up, as had the anterior drawer and Lachman tests but not the pivot-shift test. The medial MAT group showed significant improvement in side-to-side difference on Telos stress radiographs, from 6.5 mm (preoperatively) to 3.6 mm (2-year follow-up) (P = .001), while the lateral MAT group showed no significant change. There was no progression of arthritis in either group.
CONCLUSION: Medial MAT improved not only anteroposterior stability but also rotational stability in the meniscus-deficient ACL-reconstructed knee. Lateral MAT showed improvements in the anterior drawer and Lachman tests but not in the pivot-shift test or side-to-side difference on Telos stress radiographs in meniscus-deficient ACL-reconstructed knees. Instability and pain are indications for MAT in meniscus-deficient ACL-reconstructed knees.
Purpose/Hypothesis: The purpose of this study was to compare the clinical and radiologic outcomes of remnant-preserving PCL reconstruction using anatomic versus low tibial tunnels. We hypothesized that the outcomes of low tibial tunnel placement would be superior to those of anatomic tibial tunnel placement at the 2-year follow-up after remnant-preserving PCL reconstruction.
Study Design: Cohort study; Level of evidence, 3.
Methods: We retrospectively reviewed the data for patients who underwent remnant-preserving PCL reconstruction between March 2011 and January 2018 with a minimum follow-up of 2 years (N = 63). On the basis of the tibial tunnel position on postoperative computed tomography, the patients were divided into those with anatomic placement (group A; n = 31) and those with low tunnel placement (group L; n = 32). Clinical scores (International Knee Documentation Committee subjective score, Lysholm score, and Tegner activity level), range of motion, complications, and stability test outcomes at follow-up were compared between the 2 groups. Graft signal on 1-year follow-up magnetic resonance imaging scans was compared between 22 patients in group A and 17 patients in group L.
Results: There were no significant differences between groups regarding clinical scores or incidence of complications, no between-group differences in posterior drawer test results, and no side-to-side difference on Telos stress radiographs (5.2 ± 2.9 mm in group A vs 5.1 ± 2.8 mm in group L; P = .900). Postoperative 1-year follow-up magnetic resonance imaging scans showed excellent graft healing in both groups, with no significant difference between them.
Conclusion: The clinical and radiologic outcomes and complication rate were comparable between anatomic tunnel placement and low tibial tunnel placement at 2-year follow-up after remnant-preserving PCL reconstruction. The findings of this study suggest that both tibial tunnel positions are clinically feasible for remnant-preserving PCL reconstruction.