NDLI: A KRAS-variant in Ovarian Cancer Acts as a Genetic Marker of Cancer Risk

Content Provider	PubMed Central
Author	Ratner, Elena Lu, Lingeng Boeke, Marta Barnett, Rachel Nallur, Sunitha Chin, Lena J. Pelletier, Cory Rachel, Blitzblau Tassi, Renata Paranjape, Trupti Hui, Pei Godwin, Andrew K. Herbert, Yu Risch, Harvey Rutherford, Thomas Schwartz, Peter Santin, Alessandro Matloff, Ellen Daniel, Zelterman Slack, Frank J. Weidhaas, Joanne B.
Abstract	Ovarian cancer is the single most deadly form of women’s cancer, typically presenting as an advanced disease at diagnosis in part due to a lack of known risk factors or genetic markers of risk. The KRAS oncogene and altered levels of the microRNA let-7 are associated with an increased risk of developing solid tumors. In this study, we investigated a hypothesized association between an increased risk of ovarian cancer and a variant allele of KRAS at rs61764370, referred to as the KRAS-variant, that disrupts a let-7 microRNA binding site in this oncogene. Specimens obtained were tested for the presence of the KRAS-variant from non-selected ovarian cancer patients in three independent cohorts, two independent ovarian case-control studies, and ovarian cancer patients with hereditary breast and ovarian cancer syndrome (HBOC) as well as in their family members. Our results indicate that the KRAS-variant is associated with greater than 25% of non-selected ovarian cancer cases. Further, we found that it is a marker for a significant increased risk of developing ovarian cancer, as confirmed by two independent case control analyses. Lastly, we determined that the KRAS-variant was present in 61% of HBOC patients without BRCA1 or BRCA2 mutations, previously considered uninformative, as well as in their family members with cancer. Our findings strongly support the hypothesis that the KRAS-variant is a genetic marker for increased risk of developing ovarian cancer, and they suggest that the KRAS-variant may be a new genetic marker of cancer risk for HBOC families without other known genetic abnormalities.
Related Links	http://dx.doi.org/10.1158/0008-5472.CAN-10-0689
Ending Page	6515
Page Count	7
Starting Page	6509
File Format	PDF
ISSN	15387445
e-ISSN	15387445
Journal	Cancer research
Issue Number	16
Volume Number	70
Language	English
Publisher Date	2010-08-15
Access Restriction	Open
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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