Role of genetic polymorphisms and ovarian cancer susceptibility

Abstract

Risk SNP Genetic Polymorphism Early detection A B S T R A C TThe value of identifying women with an inherited predisposition to epithelial ovarian cancer has become readily apparent with the identification of the BRCA1, and BRCA2 genes.Women who inherit a deleterious mutation in either of these genes have a very high lifetime risk of ovarian cancer (10-60%) and to some extent, increased risks of fallopian tube and peritoneal cancer. These highly lethal cancers are almost completely prevented by prophylactic salpingoophorectomy. BRCA1/2 mutation testing has become the accepted standard of care in families with a strong history of breast and/or ovarian cancer. This approach has the potential to reduce ovarian cancer mortality by about 10%.Although the ability to perform genetic testing for BRCA1 and 2 represents a significant clinical advance, the frequency of mutations in these high penetrance ovarian cancer susceptibility genes is low in most populations. There is evidence to suggest that ovarian cancer susceptibility might be affected by common low penetrance genetic polymorphisms like it was shown for several common disorders like diabetes or breast cancer. Although such polymorphisms would increase risk to a lesser degree, they could contribute to the development of a greater proportion of ovarian cancers by virtue of their higher frequencies in the population. It has been shown that the most powerful approach to studying low penetrance genes is an association study rather than a linkage study design. This review describes the efforts that have been made in this field by individual case-control * Corresponding author.E-mail address: peter.fasching@uk-erlangen.de (P.A. Fasching).

Association between the XRCC3 Thr241Met Polymorphism and Risk of Colorectal Cancer: a Meta Analysis of 5,193 Cases and 6,645 Controls

“…Although a number of previous studies have reported a significant association between the XRCC3 Thr241Met polymorphism and CRC risk, others have identified no such association (Fasching et al, 2009). In order to resolve this conflict, in the current study, a meta-analysis was conducted to examine the associa¬tion between a commonly studied XRCC3 Thr241Met polymorphism and CRC risk.…”

Polymorphisms in the RANK/RANKL genes and their effect on bone specific prognosis in breast cancer patients

“…We have chosen a candidate SNP approach, selecting genes of interest and focusing on genetic variants that might have the greatest impact on the biological processes concerning transcription, translation, and function of the protein. Looking at association studies in breast and ovarian cancer this approach was not very successful and the results that were produced could not often be replicated [50]. Out of more than 75 validated breast cancer risk SNPs, only one was discovered with a candidate gene approach [8,31,51].…”

Ovarian cancer: Origin and factors involved in carcinogenesis with potential use in diagnosis, treatment and prognosis of the disease

“…Particularly in ovarian cancer these studies have failed to find relevant associations previously [73], however a recent study confirmed susceptibility locus at 9p22, revealed several candidate loci and two susceptibility loci 8q24 and 2q31 have been confirmed [74]. Several further polymorphisms investigated previously (concerning sex hormone pathways or cell cycle genes) proved not to be convincingly usable for the identifying a strong association with the disease [75,76].…”