bioRxiv Science⌕ Search

Biology subjects

Neumayer, L.

Publications and source records attributed to Neumayer, L..

2 recordsLinked to original sources
bioRxiv2017

Universal Panel Testing of Pancreatic Cancer Cases for Cancer Predisposition

Background and AimsGenes associated with hereditary breast and ovarian cancer (HBOC) and colorectal cancer (CRC) susceptibility have been shown to play a role in pancreatic cancer susceptibility. Germline genetic testing of pancreatic cancer cases could be beneficial for at-risk relatives with pathogenic variants in established HBOC and CRC genes, but it is unclear what proportion of pancreatic cancer cases harbor pathogenic variants in these genes.\n\nMethods66 pancreatic cancer cases, unselected for family history and diagnosed at the Huntsman Cancer Hospital (HCH), were sequenced on a custom 34-gene panel including known HBOC and CRC genes. A second set of 156 unselected HCH pancreatic cancer cases were sequenced on an expanded 59-gene panel (n=95) or with a custom 14-gene clinical panel (n=61). Sequencing data from both sets of pancreatic cancer cases, the pancreatic cancer cases of the Cancer Genome Atlas (TCGA), and an unselected pancreatic cancer screen from the Mayo Clinic were combined in a meta-analysis to estimate the proportion of carriers with pathogenic and variants of uncertain significance.\n\nResultsApproximately 8.9% of unselected pancreatic cancer cases at the HCH carried a variant with potential HBOC or CRC screening recommendations. A meta-analysis of unselected pancreatic cancer cases revealed that approximately 10.5% carry a pathogenic variant or HiP-VUS.\n\nConclusionWith the inclusion of both HBOC and CRC susceptibility genes in a panel test, unselected pancreatic cancer cases have a high enough percentage of carriers to rationalize genetic testing for identification of variants that could be further used in cascade testing of healthy relatives to increase HBOC and CRC surveillance measures.

genetics↗
bioRxiv2017

Population-Based Relative Risks For Specific Family History Constellations Of Breast Cancer - Towards Individualized Risk Estimation

PurposeUsing a large resource linking genealogy with decades of cancer data, RRs were estimated for breast cancer (BC) based on specific family history extending to first cousins.\n\nMethodsRRs for BC were estimated in 640,366 females with breast cancer family histories that included number of first-(FDR), second-(SDR), and third-degree relatives (TDR), maternal and paternal relatives, and age at earliest diagnosis.\n\nResultsRRs for first-degree relatives of BC cases ranged from 1.61 (=1 FDR affected, CI: 1.56, 1.67) to 5.00 ([≥]4 FDRs affected, CI: 3.35, 7.18). RRs for second degree relatives of probands with 0 affected FDRs ranged from 1.08 ([≥]1 SDR affected, CI: 1.04, 1.12) to 1.71 ([≥]4 SDRs affected, CI: 1.26, 2.27) and for second degree relatives of probands with exactly 1 FDR from 1.54 (0 SDRs affected, CI:1.47, 1.61) to 4.78 ([≥] 5 SDRs; CI 2.47, 8.35). RRs for third-degree relatives with no closer relatives affected were significantly elevated for probands with >=5 affected TDRs RR=1.32, CI: 1.11, 1.57).\n\nConclusionsThe majority of females analyzed had a family history of BC. Any number of affected FDRs or SDRs significantly increased risk for BC, and more than 4 TDRs, even with no affected FDRs or SDRs significantly increased risk. Risk prediction derived from specific and extended family history allows identification of females at highest risk even when they do not have a conventionally defined \"high risk\" family; these risks could be a powerful, efficient tool to individualize cancer prevention and screening.

genetics↗