المؤلفون: Heald, Brandie¹ (AUTHOR) brandie.leach@invitae.com, Pirzadeh-Miller, Sara² (AUTHOR), Ellsworth, Rachel E¹ (AUTHOR), Nielsen, Sarah M¹ (AUTHOR), Russell, Emily M¹ (AUTHOR), Beitsch, Peter¹ (AUTHOR), Esplin, Edward D¹ (AUTHOR), Nussbaum, Robert L¹ (AUTHOR), Pineda-Alvarez, Daniel E¹ (AUTHOR), Kurian, Allison W³ (AUTHOR), Hampel, Heather⁴ (AUTHOR)

المصدر: JNCI: Journal of the National Cancer Institute. Feb2024, Vol. 116 Issue 2, p334-337. 4p.

مصطلحات موضوعية: *CANCER genes, *EARLY detection of cancer, *RELATIVES, *GENETIC variation, *GERM cells

مستخلص: Current guidelines recommend single variant testing in relatives of patients with known pathogenic or likely pathogenic germline variants in cancer predisposition genes. This approach may preclude the use of risk-reducing strategies in family members who have pathogenic or likely pathogenic germline variants in other cancer predisposition genes. Cascade testing using multigene panels was performed in 3696 relatives of 7433 probands. Unexpected pathogenic or likely pathogenic germline variants were identified in 230 (6.2%) relatives, including 144 who were negative for the familial pathogenic or likely pathogenic variant but positive for a pathogenic or likely pathogenic variant in a different gene than the proband and 74 who tested positive for the familial pathogenic or likely pathogenic variant and had an additional pathogenic or likely pathogenic variant in a different gene than the proband. Of the relatives with unexpected pathogenic or likely pathogenic germline variants, 36.3% would have qualified for different or additional cancer screening recommendations. Limiting cascade testing to only the familial pathogenic or likely pathogenic variant would have resulted in missed, actionable findings for a subset of relatives. [ABSTRACT FROM AUTHOR]

المؤلفون: Forkosh, Esther, Bergel, Michael, Hatchell, Kathryn E., Nielsen, Sarah M., Heald, Brandie, Benson, Ariel A., Friedman, Eitan, Esplin, Edward D., Katz, Lior H.

المصدر: Cancers; Dec2022, Vol. 14 Issue 23, p5875, 9p

مصطلحات موضوعية: STOMACH tumors, PANCREATIC tumors, BLADDER tumors, GENETIC mutation, CONFIDENCE intervals, OVARIAN tumors, MELANOMA, GENETIC testing, LUNG tumors, COLORECTAL cancer, CANCER patients, GENETIC markers, CHI-squared test, DESCRIPTIVE statistics, HEMATOLOGIC malignancies, KIDNEY tumors, TUMOR markers, DATA analysis software, ODDS ratio, BREAST tumors, PROSTATE tumors, DISEASE risk factors

مستخلص: Simple Summary: APC I1307K has a two-fold increased risk for colorectal cancer in Ashkenazi Jews (AJ) compared to non-Jewish populations. The study aims to demonstrate the prevalence of the APC I1307K variant in the largest cohort of AJ and non-AJ white (NAW) descents described so far. In addition, we assessed the prevalence of CRC and extracolonic malignancies among I1307K carriers. We found that NAW I1307K carriers had a higher risk of any cancer, such as CRC, melanoma, breast, and prostate cancer. Among AJ, the variant increased the risk for CRC and renal cancer, and AJ men had a higher risk for any cancer and melanoma. We believe these findings are significant and may suggest the necessity for cancer screening in this population. Purpose: APC I1307K has a higher prevalence among Ashkenazi Jews (AJ), and a two-fold increased risk for colorectal cancer (CRC) compared to non-Jewish populations. We assessed CRC and extracolonic malignancies among I1307K carriers from AJ and non-AJ whites (NAW). Methods: We compared the rate of I1307K in cancer patients who underwent germline genetic testing via a multi-gene panel with healthy subjects retrieved from the gnomAD database. Cases undergoing testing were not selected and testing was undertaken through a commercial laboratory. Results: Overall, 586/7624 (7.6%) AJ with cancer carried I1307K compared to 342/4918 (6.9%) in the AJ control group (p = NS). In the NAW, 318/141,673 (0.2%) cancer patients and 73/58,918 (0.1%) controls carried the variant [OR = 1.8, (95% CI 1.41–2.35), p < 0.001]. I1307K in NAW was associated with an increased risk of CRC [OR = 1.95, (95% CI 1.39–2.73), p < 0.01], melanoma [OR = 2.54, (95% CI 1.57–3.98)], breast [females, OR = 1.73, (95% CI 1.18–2.65), p < 0.01], and prostate cancer [males, OR = 2.42, (95% CI 1.45–3.94), p < 0.01]. Among AJ, the variant increased the risk for CRC [OR = 1.67, (95% CI 1.36–2.05), p < 0.001] and renal cancer [OR = 1.64, (95% CI 1.04–2.47)]. AJ men had a higher risk for any cancer [OR = 1.32, (95% CI 1.05–1.66), p < 0.05] and melanoma [OR = 2.04, (95% CI 1.24–3.22); p < 0.05]. Conclusions: This is the most extensive study to date conducted on I1307K carriers, although it is amenable to selection bias. NAW carrying I1307K had a higher risk of any cancer and several specific cancer types, whereas AJ carrying the variant had a risk for only a few select cancers. Our data add to the research base on I1307 carriers concerning future risk management. [ABSTRACT FROM AUTHOR]

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