METHODS: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry.
RESULTS: In European ancestry samples, 14 genes were significantly associated (q
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: Search was performed using a MEDLINE, EMBASE, and Cochrane database, and each of the selected studies was evaluated for methodological quality using a risk of bias (ROB) covering 7 criteria. Clinical and radiological outcomes with more than 5 years of follow-up were evaluated after surgical treatment of DLM. They were analyzed according to the age, follow-up period, kind of surgery, DLM type, and alignment.
RESULTS: Eleven articles (422 DLM cases) were included in the final analysis. Among 7 criteria, 3 criteria showed little ROB in all studies. However, 4 criteria showed some ROB ("Yes" in 63.6% to 81.8%). The minimal follow-up period was 5.5 years (weighted mean follow-up: 9.1 years). Surgical procedures were performed with open or arthroscopic partial central meniscectomy, subtotal meniscectomy, total meniscectomy, or partial meniscectomy with repair. The majority of the studies showed good clinical results. Mild joint space narrowing was reported in the lateral compartment, but none of the knees demonstrated moderate or advanced degenerative changes. Increased age at surgery, longer follow-up period, and subtotal or total meniscectomy could be related to degenerative change. The majority of the complications was osteochondritis dissecans at the lateral femoral condyle (13 cases) and reoperation was performed by osteochondritis dissecans (4 cases), recurrent swelling (2 cases), residual symptom (1 case), stiffness (1 case), and popliteal stenosis (1 case).
CONCLUSIONS: Good clinical results were obtained with surgical treatment of symptomatic DLM. The progression of degenerative change was minimal and none of the knees demonstrated moderate or advanced degenerative changes. Increased age at surgery, longer follow-up period, and subtotal or total meniscectomy were possible risk factors for degenerative changes.
LEVEL OF EVIDENCE: Level IV, systematic review of Level IV studies.
MATERIALS AND METHODS: Results that are possible to be compared in more than two articles were presented as forest plots. A 95% confidence interval was calculated for each effect size, and we calculated the I 2 statistic, which presents the percentage of total variation attributable to the heterogeneity among studies. The random effects model was used to calculate the effect size.
RESULTS: Seven articles were included to the final analysis. Case groups were composed of HTO without concurrent procedures and control groups were composed of HTO with concurrent procedures such as marrow stimulation procedure, mesenchymal stem cell transplantation, and injection. The case group showed a higher hospital for special surgery score and mean difference was 4.10 [I 2 80.8%, 95% confidence interval (CI) - 9.02 to 4.82]. Mean difference of the mechanical femorotibial angle in five studies was 0.08° (I 2 0%, 95% CI - 0.26 to 0.43). However, improved arthroscopic, histologic, and MRI results were reported in the control group.
CONCLUSION: Our analysis support that concurrent procedures during HTO for medial compartment OA have little beneficial effect regarding clinical and radiological outcomes. However, they might have some beneficial effects in terms of arthroscopic, histologic, and MRI findings even though the quality of healed cartilage is not good as that of original cartilage. Therefore, until now, concurrent procedures for medial compartment OA have been considered optional. Nevertheless, no conclusions can be drawn for younger patients with focal cartilage defects and concomitant varus deformity. This question needs to be addressed separately.
METHODS: A total of 12,901 breast cancer cases and 12,583 controls from 12 case-control studies were included in our pooled analysis. HLA imputation was performed using SNP2HLA on 10,886 quality-controlled variants within the 15-55 Mb region on chromosome 6. HLA alleles (n = 175) with info scores greater than 0.8 and frequencies greater than 0.01 were included (resolution at two-digit level: 71; four-digit level: 104). We studied the associations between HLA alleles and breast cancer risk using logistic regression, adjusting for population structure and age. Associations between HLA alleles and the risk of subtypes of breast cancer (ER-positive, ER-negative, HER2-positive, HER2-negative, early-stage, and late-stage) were examined.
RESULTS: We did not observe associations between any HLA allele and breast cancer risk at P
METHODS: Of these 279 variants, data were obtained for 228 from GWAS conducted within the Asian Breast Cancer Consortium (24,206 cases and 24,775 controls) and the Breast Cancer Association Consortium (122,977 cases and 105,974 controls of European ancestry). Meta-analyses were conducted to combine the results from these two datasets.
FINDINGS: Of those 228 variants, an association was observed for 12 variants in 10 genes at a Bonferroni-corrected threshold of P