Benefits of offering genetic testing at the time of endometrial cancer diagnosis include, but are not limited to, the following:

1. Surgery: The most common treatment for a newly diagnosed endometrial cancer includes hysterectomy with removal of the ovaries and fallopian tubes, as well as assessment of lymph nodes.An exception to this practice might apply to a younger woman who wishes to retain fertility or retain her adnexa. Immunohistochemistry of endometrial sampling may allow for an assessment of the likelihood of a heritable genetic variant at the time of diagnosis, which may add value to the surgical decision-making process. For a young woman who is found to have Lynch syndrome, knowledge of this information may help guide a decision for hormonal management of endometrial cancer to allow future childbearing, or salpingo-oophorectomy if her risk of ovarian cancer is deemed high enough on the basis of a specific genetic variant. For a young woman who is found to carry a pathogenic variant in BRCA1/BRCA2, or one of the other homologous recombination deficiencies increasing ovarian cancer risk, she may wish to decide between salpingo-oophorectomy or, at least, salpingectomy.
2. Chemotherapy and other biologics: Immune checkpoint inhibitors are now approved for use in endometrial cancers that have MSI or MMR deficiency.While MSI and MMR status can be assessed at either the time of diagnosis or recurrent disease, it may be beneficial to perform tumor testing at diagnosis with the primary pathology processing, usually at the time of hysterectomy.

.This increased the total number of independent signals in known susceptibility loci to 94. Variation in these loci was estimated to account for approximately 16% of familial breast cancer risk.Although most early GWAS studies had small sample sizes by today's standards, studies improved power by enriching for family history, performing meta-analyses, and evaluating marginally significant GWAS SNPs in larger populations. For example, 925 SNPs displaying near genome-wide significant association with breast cancer in the initial study by Easton and colleagues were further evaluated by BCAC using 37,012 cases and 40,069 controls resulting in two new susceptibility loci at 3p24 near SLC4A7 and NEK10 and at 17q23.2 near COX11 . Additional efforts by the Shanghai Breast Cancer study in a three-stage study also identified risk-associated SNPs in the ESR1 locus; these SNPs were replicated in an independent study of European women from BCAC. Furthermore, 72 potential breast cancer SNPs that did not reach genome-wide significance in pooled data from two GWAS (UK2 and British Breast Cancer Study; BBCS) were evaluated using cases and controls from 41 studies in BCAC and 9 individual GWAS. One SNP on 12p11 near PTHLH (rs10771399) was associated with overall breast cancer risk, and two others (rs1292011on 12q24; rs2823093 on 21q21 near NRIP1) associated with ER-positive breast cancer risk . Subsequently, five additional breast cancer susceptibility loci were identified in a multistage GWAS that included 3,659 cases with a family history of breast cancer and 4,897 controls . Similarly, Fletcher and colleagues identified a new susceptibility locus at 9q31.2 in a GWAS including 1,694 cases with a personal and/or family history of breast cancer compared with 2,365 controls. The most recent and largest breast cancer GWAS used the Illumina OncoArray Bead Chip, which included approximately 570,000 SNPs and was imputed to approximately 11.8 million. From BCAC, 61,282 breast cancer cases and 45,494 controls of European ancestry were genotyped on the OncoArray platform and results were used in a meta-analysis including data from iCOGS and 11 GWAS studies . In total, 122,977 breast cancer cases and 105,974 controls of European ancestry were analyzed along with 14,068 breast cancer cases and 13,104 controls of East Asian ancestry. In this study, SNPs from 49 previously identified breast cancer loci were replicated with genome-wide significance (P < 5 × 10-8), and SNPs from another 50 known risk loci did not reach but were associated with breast cancer . In addition, 65 new breast cancer risk loci (also genome-wide significant) were identified for women of European ancestry.

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General Surgery: Open Access