Ethical failings: The problematic history of cancer risk assessment

Purpose A detailed family history is important for cancer risk assessment, but obtaining it is time consuming and infrequently accomplished in practice. The Genetic Risk Easy Assessment Tool (GREAT) conducts a computer-administered family history interview and immediately generates a pedigree diagram in digital form. The purpose of this study was to validate family cancer histories produced by patients using the computer tool in comparison with pedigrees made by genetic counselors. Methods Patients scheduled for genetics consultation recorded their family histories using the GREAT, separate from their genetic counseling session. The presence of each relative; presence, type, and age at diagnosis of cancers; and cancer geneticist's risk assessment were compared for 120 pairs of pedigrees produced by counselors versus computer tool. Results The automated telephone interview took a mean of 33.5 minutes and was highly acceptable to respondents. Ninety-four percent of first-degree relatives, 67% of second-degree relatives, and 38% of third-degree relatives were identical on paired pedigrees; computer-generated pedigrees included additional relatives. Sixty-three percent of all cancers were identified by both family histories, with 90% agreement on the type of cancer. There was very good agreement (κ = 0.70; correlation = 0.77) between the geneticist's breast cancer risk assessments based on computer versus counselors' pedigrees. In a subsample of 61 users, test-retest reliability for the computer-administered questionnaire was high (φ = 0.94 for cancers in first-degree and φ = 0.91 in second-degree relatives). Conclusion The GREAT computer-administered questionnaire provides an acceptable, reliable, and valid way of collecting an unverified but extensive family history of cancer and displaying it as a pedigree, in an entirely automated process.

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Tobacco use among individuals presenting for cancer risk assessment

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.1547 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 1547-1547

Author(s):

W. Shen ◽

L. F. Ross ◽

L. Patrick-Miller ◽

O. I. Olopade ◽

S. A. Cummings ◽

...

Keyword(s):

Risk Assessment ◽

Cancer Risk ◽

Tobacco Use ◽

Tobacco Cessation ◽

Cancer Risk Assessment ◽

Screening Colonoscopy ◽

Future Research ◽

Racial Groups ◽

Clinical Encounters ◽

History Of

1547 Background: An important component of cancer risk assessment (CRA) is the evaluation of exposures and preventive health behaviors. Tobacco use (TU) remains a significant contributor to cancer risk and decreasing tobacco use is a major national health objective. Methods: Clinical charts were reviewed to evaluate the incidence of TU and characteristics of tobacco users (TUs) among individuals presenting to the University of Chicago Cancer Risk Clinic for cancer risk assessment (CRA). Results: Among 98 individuals (97% female) presenting for CRA from 12/05–10/06, 51% (50/98) reported no TU, 38% (37/98) reported prior TU and 11% (11/98) reported current TU. Current tobacco users included 10% (7/73) of whites and 18% (4/22) of blacks with no TU among other racial groups (0/3). 45% of TUs (5/11) had a personal history of cancer. 45% of TUs reported compliance with self-breast examination, 73% with cervical cancer screening. Among TUs over 40 years old (YO), 67% (6/9) reported a mammogram in the last year and the 2 TUs over 50 YO reported a screening colonoscopy. All TUs reported interest in tobacco cessation interventions. Conclusions: Tobacco use among individuals presenting for CRA is lower than reported general population rates of TU (23%). Despite this, a proportion of individuals presenting for CRA report current TU, despite engaging in other cancer prevention behaviors. Continued review of clinical encounters from 2004- 06 (n=425) will allow for multi-variate analysis of predictors of current TU, which will inform future research employing cancer risk assessment encounters as “teachable moments” to optimize tobacco cessation outcomes. No significant financial relationships to disclose.

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Prevalence of pathogenic variants in DNA damage response and repair genes in patients undergoing cancer risk assessment and reporting a personal history of early-onset renal cancer

Scientific Reports ◽

10.1038/s41598-020-70449-5 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Tiffiney R. Hartman ◽

Elena V. Demidova ◽

Randy W. Lesh ◽

Lily Hoang ◽

Marcy Richardson ◽

...

Keyword(s):

Risk Assessment ◽

Dna Damage ◽

Cancer Risk ◽

Dna Damage Response ◽

Personal History ◽

Cancer Risk Assessment ◽

Pathogenic Variants ◽

Damage Response ◽

History Of ◽

Repair Genes

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The Mistaken Birth and Adoption of LNT: An Abridged Version

Dose-Response ◽

10.1177/1559325817735478 ◽

2017 ◽

Vol 15 (4) ◽

pp. 155932581773547 ◽

Cited By ~ 6

Author(s):

Edward J. Calabrese

Keyword(s):

Risk Assessment ◽

Cancer Risk ◽

Biological Effects ◽

Gene Mutations ◽

Cancer Risk Assessment ◽

Regulatory Agencies ◽

National Academy Of Sciences ◽

The Us ◽

History Of ◽

Academy Of Sciences

The historical foundations of cancer risk assessment were based on the discovery of X-ray-induced gene mutations by Hermann J. Muller, its transformation into the linear nonthreshold (LNT) single-hit theory, the recommendation of the model by the US National Academy of Sciences, Biological Effects of Atomic Radiation I, Genetics Panel in 1956, and subsequent widespread adoption by regulatory agencies worldwide. This article summarizes substantial recent historical revelations of this history, which profoundly challenge the standard and widely acceptable history of cancer risk assessment, showing multiple significant scientific errors and incorrect interpretations, mixed with deliberate misrepresentation of the scientific record by leading ideologically motivated radiation geneticists. These novel historical findings demonstrate that the scientific foundations of the LNT single-hit model were seriously flawed and should not have been adopted for cancer risk assessment.

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Development and validation of the PREMMplus clinical prediction model for multigene hereditary cancer risk assessment.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.1579 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 1579-1579

Author(s):

Matthew B. Yurgelun ◽

Hajime Uno ◽

C. Sloane Furniss ◽

Chinedu I. Ukaegbu ◽

Miki Horiguchi ◽

...

Keyword(s):

Risk Assessment ◽

Cancer Risk ◽

Cancer Susceptibility ◽

Cancer Risk Assessment ◽

Clinical Prediction ◽

Clinical Prediction Model ◽

Risk Genes ◽

Pathogenic Variants ◽

Cancer Susceptibility Genes ◽

History Of

1579 Background: Current clinical prediction models provide syndrome-specific numeric estimates of an individual's likelihood of having a specific hereditary cancer syndrome (e.g., PREMM5 for Lynch syndrome; BRCAPRO for BRCA1/2). With the emergence of multigene panel testing (MGPT), there is a need to evaluate individuals' risk of carrying a pathogenic variant in a diverse array of cancer susceptibility genes in parallel. This study’s aim was to develop and validate the PREMMplus clinical prediction model for multigene cancer risk assessment. Methods: PREMMplus was developed in a cohort of 7296 individuals who had undergone germline MGPT at a single center. Logistic regression models were used to examine candidate predictive variables – including age, sex, ethnicity, and personal/family history of cancer – to provide a numeric estimate of an individual’s likelihood of carrying a pathogenic/likely pathogenic germline variant in one of 18 cancer susceptibility genes (11 high- [ APC, BRCA1/2, CDH1, EPCAM, MLH1, MSH2, MSH6, biallelic MUTYH, PMS2, and TP53] and 7 moderate-penetrance [ ATM, CDKN2A, CHEK2, PALB2, PTEN, RAD51C, and RAD51D]). Model performance was validated in an independent dataset of 14845 individuals who had undergone MGPT at a commercial laboratory. Results: Using clinical characteristics, including personal/family history of 18 cancers plus colorectal adenoma burden, PREMMplus demonstrated an excellent ability to predict pathogenic variants in high penetrance genes at 90% sensitivity. PREMMplus had acceptable performance with the addition of 7 moderate penetrance genes. PREMMplus was well-calibrated and demonstrated comparable performance in the external validation dataset. Conclusions: PREMMplus is the first validated risk assessment model to quantify an individual’s likelihood of carrying pathogenic variants in a wide diversity of cancer risk genes, and can be used to select individuals who should undergo MGPT. As expected, PREMMplus’s discriminatory capacity was reduced with the inclusion of moderate penetrance cancer risk genes. [Table: see text]

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