TY - JOUR

T1 - The prospect of discovering new biomarkers for ovarian cancer based on current knowledge of susceptibility loci and genetic variation

AU - Christophersen, Mikael Kronborg

AU - Høgdall, Claus

AU - Høgdall, Estrid

PY - 2019

Y1 - 2019

N2 - Ovarian cancer is the most lethal gynaecological malignancy. The cancer initially presents with non‑specific symptoms; thus, it is typically not discovered until the patient has reached the late, considerably more lethal, stages of the disease. Research focus is currently on finding novel biomarkers, especially for early detection and stratification of the disease. One promising approach has been to focus on mutations or variations in the genetic code that are associated with the risk of developing ovarian cancer. A certain heritable component is already known regarding genes such as BRCA1/2, TP53, MSH6, BRIP1 and RAD51C, yet these are estimated to only account for ~3.1% of the total risk. Recent advances in sequencing technologies have enabled the investigation of hundreds of thousands of genetic variants in genome‑wide association studies in tens of thousands of patients, which has led to the discovery of 108 (39 loci with P<5.0x10‑8) novel susceptibility loci for ovarian cancer, presented in this review. Using the published variants in a patient cohort screening, together with variants identified in our ongoing whole exome sequencing project, future aims are to ascertain whether certain of the novel variants could be used as biomarkers for early diagnosis and/or treatment decisions.

AB - Ovarian cancer is the most lethal gynaecological malignancy. The cancer initially presents with non‑specific symptoms; thus, it is typically not discovered until the patient has reached the late, considerably more lethal, stages of the disease. Research focus is currently on finding novel biomarkers, especially for early detection and stratification of the disease. One promising approach has been to focus on mutations or variations in the genetic code that are associated with the risk of developing ovarian cancer. A certain heritable component is already known regarding genes such as BRCA1/2, TP53, MSH6, BRIP1 and RAD51C, yet these are estimated to only account for ~3.1% of the total risk. Recent advances in sequencing technologies have enabled the investigation of hundreds of thousands of genetic variants in genome‑wide association studies in tens of thousands of patients, which has led to the discovery of 108 (39 loci with P<5.0x10‑8) novel susceptibility loci for ovarian cancer, presented in this review. Using the published variants in a patient cohort screening, together with variants identified in our ongoing whole exome sequencing project, future aims are to ascertain whether certain of the novel variants could be used as biomarkers for early diagnosis and/or treatment decisions.

U2 - 10.3892/ijmm.2019.4352

DO - 10.3892/ijmm.2019.4352

M3 - Review

C2 - 31573049

VL - 44

SP - 1599

EP - 1608

JO - International Journal of Molecular Medicine

JF - International Journal of Molecular Medicine

SN - 1107-3756

IS - 5

ER -