Dataset Information

Genetic variants in matrix metalloproteinase genes as disposition factors for ovarian cancer risk, survival, and clinical outcome.

ABSTRACT: Ovarian cancer is one of the leading female cancers in the United States. Challenges remain in early diagnosis of this deadly disease. Matrix metalloproteinases (MMPs) family genes are paradoxically involved in cancer promotion and suppression. We hypothesize that genetic variants in MMP genes are associated with ovarian cancer development, so they could be potential markers for ovarian cancer diagnosis and prognosis. In this study of 417 ovarian cancer cases and 417 healthy controls, we genotyped a comprehensive panel of 266 single nucleotide polymorphisms (SNPs) in 23 MMP genes and analysed their associations with ovarian cancer risk, overall survival and treatment response in ovarian cancer cases who received platinum-based chemotherapy with surgery. In the analysis on 339 Caucasian cases and 349 Caucasian controls, 4 SNPs were significantly associated with cancer risk. The most significant association was observed for rs2292730 (OR = 2.03, 95% CI = 1.39-2.96, P = 0.0002). Classification and regression tree analysis identified four terminal nodes with differential risk of ovarian cancer. Thirty-four SNPs were significantly associated with overall survival and four of which showed significant association with response to chemotherapy. Unfavourable genotype analysis of top SNPs on overall risk of death showed significant gene-dosage effect, survival tree analysis differentiated patients into distinct risk groups based on their genetic profiles with median survival times (MSTs) ranging from 17.7 to 151.7 months. In conclusion, our results suggest that genetic variants in MMP pathway genes may modulate the risk and clinical outcomes of ovarian cancer, both individually and jointly.

SUBMITTER: Wang Y

PROVIDER: S-EPMC4869714 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Multicentric Osteolysis, Nodulosis, and Arthropathy (MONA) syndrome is a rare genetic skeletal dysplasia. Its diagnosis can be deceptively similar to childhood-onset genetic skeletal dysplasias and juvenile idiopathic arthritis. We aimed to report the syndrome's clinical and radiologic features with emphasis on skeletal manifestations. And establish relevant phenotype-genotype correlations. We evaluated two boys, 4-and-7-years-old with MONA syndrome. Both patients had consanguineous parents. We verified the diagnosis by correlating the outcomes of clinical, radiologic and molecular analysis. We specifically evaluated the craniofacial morphology and clinical and radiographic skeletal abnormalities. We contextualized the resultant phenotype-genotype correlations to publications on MONA and its differential diagnosis. Skeletal manifestations were the presenting symptoms and mostly restricted to hands and feet in terms of fixed extension deformity of the metacarpophalangeal and flexion deformity of the interphalangeal joints with extension deformity of big toes. There were arthritic symptoms in the older patient especially of the wrists and minute pathologic fractures. The skeletal radiographs showed osteopenia/dysplastic changes of hands and feet. Both patients had variants in the matrix metalloproteinase2 gene which conformed to phenotype of previously reported literature in one patient while the other had a novel variant which conformed to MONA phenotype. Craniofacial abnormalities were present. However, minimal extra-skeletal manifestations. Overall, there is an emerging distinctive skeletal pattern of involvement in terms of both clinical and radiographic features. This includes age of onset and location of presenting skeletal manifestations, chronological order of joint affection, longitudinal disease progression, specifics of skeletal radiographic pathology and craniofacial features. Nevertheless, physicians are cautioned against differential diagnosis of similar genetic skeletal dysplasias and juvenile idiopathic arthritis.

Dataset Information

Genetic variants in matrix metalloproteinase genes as disposition factors for ovarian cancer risk, survival, and clinical outcome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets