Open AccessHereditary Factors in Gynecologic Cancer
Author(s) -
Lynch Henry T.,
Casey Murray Joseph,
Shaw Trudy G.,
Lynch Jane F.
Publication year - 1998
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1634/theoncologist.3-5-319
Subject(s) - lynch syndrome , medicine , ovarian cancer , genetic counseling , cancer , endometrial cancer , genetic testing , uterine cancer , colorectal cancer , germline mutation , family history , breast cancer , population , oncology , mutation , gynecology , genetics , dna mismatch repair , biology , gene , environmental health
Cancer predisposition in some families is known to be the result of germ‐line mutations. The most noteworthy hereditary gynecologic cancer syndromes include hereditary breast‐ovarian cancer (HBOC) syndrome, wherein BRCA1 and BRCA2 germ‐line mutations have been identified, and hereditary nonpolyposis colorectal cancer (HNPCC) of the Lynch syndrome II variant, wherein hMSH2 , hMLH1 , hPMS2 , hMSH3 , and hMSH6 germ‐line mutations have been identified. DNA testing for specific cancer‐associated germ‐line mutations is now available for HBOC and HNPCC syndrome family members who are in the direct line of inheritance. Genetic counseling is mandatory prior to DNA testing and at the time of disclosure of findings. A patient found to be negative for the family's particular cancer‐associated germ‐line mutation can revert to general population screening recommendations. When a deleterious mutation is identified, the physician is able to predict a patient's lifetime susceptibility to breast and ovarian carcinomas in the HBOC syndrome or the cancers which characterize the Lynch syndrome II variant of HNPCC, particularly carcinomas of the colon, endometrium, and ovary. Management strategies can be offered which are designed to take advantage of the natural history of that distinct hereditary cancer syndrome. We discuss the unfolding developments concerning familial and heritable susceptibilities, molecular genetics, and possible carcinogenic co‐factors of the three most common gynecologic cancers: carcinomas of the uterine cervix, endometrium, and ovary. We offer rationales for management based on current epidemiologic and clinical data and emerging technologies.