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Genomic Risk Factors for Cervical Cancer.

ABSTRACT: Cervical cancer is the fourth common cancer amongst women worldwide. Infection by high-risk human papilloma virus is necessary in most cases, but not sufficient to develop invasive cervical cancer. Despite a predicted genetic heritability in the range of other gynaecological cancers, only few genomic susceptibility loci have been identified thus far. Various case-control association studies have found corroborative evidence for several independent risk variants at the 6p21.3 locus (HLA), while many reports of associations with variants outside the HLA region remain to be validated in other cohorts. Here, we review cervical cancer susceptibility variants arising from recent genome-wide association studies and meta-analysis in large cohorts and propose 2q14 (PAX8), 17q12 (GSDMB), and 5p15.33 (CLPTM1L) as consistently replicated non-HLA cervical cancer susceptibility loci. We further discuss the available evidence for these loci, knowledge gaps, future perspectives, and the potential impact of these findings on precision medicine strategies to combat cervical cancer.

SUBMITTER: Ramachandran D

PROVIDER: S-EPMC8533931 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Genomic Risk Factors for Cervical Cancer.

Ramachandran Dhanya D Dörk Thilo T

Cancers 20211013 20

Cervical cancer is the fourth common cancer amongst women worldwide. Infection by high-risk human papilloma virus is necessary in most cases, but not sufficient to develop invasive cervical cancer. Despite a predicted genetic heritability in the range of other gynaecological cancers, only few genomic susceptibility loci have been identified thus far. Various case-control association studies have found corroborative evidence for several independent risk variants at the 6p21.3 locus (HLA), while m ...[more]

PMID: 34680286

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Project description:Background: The most common metastatic site in cervical cancers is lung. The aim of this study is to identify cervical cancer patients with high risk for developing lung metastasis and further explore their prognosis. Materials and Methods: At first, patients diagnosed with cervical cancer from 2010 to 2015 were identified from The Surveillance, Epidemiology, and End Results (SEER) database. Multivariate logistic and Cox regression models were used to identify risk and prognostic factors in cervical cancer patients with lung metastasis. Besides, the clinical characteristics of 14 cervical cancer patients followed up for five years with only lung metastases treated at the First Affiliated Hospital of Wenzhou Medical University were retrospectively analyzed. Results: 19,377 cervical cancer patients were selected from the SEER database; the incidence of lung metastases is 4.33%. Multivariable analysis indicated that advantage age (p<0.001), non-squamous type (p<0.001), late stage (p<0.001), lymph nodes metastases (p<0.001), and poor differentiation (p<0.003) were associated with increased risks for developing lung metastasis. Survival analysis showed that adenocarcinoma, as well as bone and liver metastases were associated with shorter survival in multivariate Cox regression. Among 14 cervical cancer patients with only lung metastasis treated in our hospital, seven patients died within median follow-up time of 16.5 months, including six patients with multiple lung metastasis lesions and one patient with solitary lesion. Seven patients received pulmonary metastasectomy and the following cisplatin-based chemotherapy, among whom one patient died during follow up. Conclusions: Lung metastasis has poor prognosis. Senior age, non-squamous type, late stage, lymph nodes metastases, and poor differentiation are associated with an increased risk for lung metastasis. We recommend pulmonary imaging assessment within 2 years after primary treatment. Adenocarcinoma and multiple pulmonary lesions might predict poor prognosis. To those patients with resectable lung metastasis lesion and no other organ involvement, metastasectomy might improve survival.

Dataset Information

Genomic Risk Factors for Cervical Cancer.

Publications

Genomic Risk Factors for Cervical Cancer.

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