PURPOSE: Multiple-gene, next-generation sequencing panels are increasingly used to assess hereditary cancer risks of patients with diverse personal and family cancer histories. The magnitude of breast and ovarian cancer risk associated with many clinically tested genes, and independent of family cancer history, remains to be quantified. METHODS: We queried a commercial laboratory database of 95,561 women tested clinically for hereditary cancer risk with a 25-gene (APC, ATM, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CHEK2, MLH2, MSH2, MSH6, MUTYH, NBN, P14ARF, P16, PALB2, PMS2, PTEN, RAD51C, RAD51D, SMAD4, STK11, and TP53) next-generation sequencing panel. Multivariable logistic regression models accounting for family history were used to examine the association between pathogenic mutations and breast or ovarian cancer. As a confirmatory approach, a matched case-control analysis was conducted, defining cases as patients with breast or ovarian cancer and controls as women without cancer. RESULTS: One or more pathogenic mutations were detected in 6,775 (7%) of 95,561 women. Eight genes (ATM, BARD1, BRCA1, BRCA2, CHEK2, PALB2, PTEN, and TP53) were associated with breast cancer, with odds ratios (ORs) ranging from two-fold (ATM: OR, 1.74; 95% CI, 1.46 to 2.07) to six-fold (BRCA1: OR, 5.91; 95% CI, 5.25 to 6.67). Eleven genes (ATM, BRCA1, BRCA2, BRIP1, MLH1, MSH2, MSH6, NBN, STK11, RAD51C, and RAD51D) were associated with ovarian cancer, with OR ranging from two-fold (ATM: OR, 1.69; 95% CI, 1.19 to 2.40) to 40-fold (STK11: OR, 41.9; 95% CI, 5.55 to 315). Multivariable models and matched case-control analyses yielded similar results. CONCLUSION: Among nearly 100,000 clinically tested women, 7% carried a pathogenic mutation in one or more cancer-associated genes. Associated breast and ovarian cancer risks ranged from two- to 40-fold after controlling for family history. These results may inform cancer risk counseling.
PURPOSE: Multiple-gene, next-generation sequencing panels are increasingly used to assess hereditary cancer risks of patients with diverse personal and family cancer histories. The magnitude of breast and ovarian cancer risk associated with many clinically tested genes, and independent of family cancer history, remains to be quantified. METHODS: We queried a commercial laboratory database of 95,561 women tested clinically for hereditary cancer risk with a 25-gene (APC, ATM, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CHEK2, MLH2, MSH2, MSH6, MUTYH, NBN, P14ARF, P16, PALB2, PMS2, PTEN, RAD51C, RAD51D, SMAD4, STK11, and TP53) next-generation sequencing panel. Multivariable logistic regression models accounting for family history were used to examine the association between pathogenic mutations and breast or ovarian cancer. As a confirmatory approach, a matched case-control analysis was conducted, defining cases as patients with breast or ovarian cancer and controls as women without cancer. RESULTS: One or more pathogenic mutations were detected in 6,775 (7%) of 95,561 women. Eight genes (ATM, BARD1, BRCA1, BRCA2, CHEK2, PALB2, PTEN, and TP53) were associated with breast cancer, with odds ratios (ORs) ranging from two-fold (ATM: OR, 1.74; 95% CI, 1.46 to 2.07) to six-fold (BRCA1: OR, 5.91; 95% CI, 5.25 to 6.67). Eleven genes (ATM, BRCA1, BRCA2, BRIP1, MLH1, MSH2, MSH6, NBN, STK11, RAD51C, and RAD51D) were associated with ovarian cancer, with OR ranging from two-fold (ATM: OR, 1.69; 95% CI, 1.19 to 2.40) to 40-fold (STK11: OR, 41.9; 95% CI, 5.55 to 315). Multivariable models and matched case-control analyses yielded similar results. CONCLUSION: Among nearly 100,000 clinically tested women, 7% carried a pathogenic mutation in one or more cancer-associated genes. Associated breast and ovarian cancer risks ranged from two- to 40-fold after controlling for family history. These results may inform cancer risk counseling.
Authors: Whitney Espinel; Marjan Champine; Heather Hampel; Joanne Jeter; Kevin Sweet; Robert Pilarski; Rachel Pearlman; Kate Shane; Pamela Brock; Judith A Westman; Lindsay Kipnis; Jilliane Sotelo; Anu Chittenden; Samantha Culver; Jill E Stopfer; Katherine A Schneider; Rosalba Sacca; Diane R Koeller; Shraddha Gaonkar; Erica Vaccari; Sarah Kane; Scott T Michalski; Shan Yang; Sarah M Nielsen; Sara L Bristow; Stephen E Lincoln; Robert L Nussbaum; Edward D Esplin Journal: Cancers (Basel) Date: 2022-05-13 Impact factor: 6.575
Authors: Ying L Liu; Kelsey Breen; Amanda Catchings; Megha Ranganathan; Alicia Latham; Deborah J Goldfrank; Rachel N Grisham; Kara Long Roche; Melissa K Frey; Dennis S Chi; Nadeem Abu-Rustum; Carol Aghajanian; Kenneth Offit; Zsofia K Stadler Journal: JCO Oncol Pract Date: 2021-09-28
Authors: Anna Gardiner; John Kidd; Maria C Elias; Kayla Young; Brent Mabey; Nassim Taherian; Shelly Cummings; Mokenge Malafa; Eric Rosenthal; Jennifer B Permuth Journal: J Natl Cancer Inst Date: 2022-07-11 Impact factor: 11.816
Authors: Orestis Tsonis; Fani Gkrozou; Konstantinos Vlachos; Minas Paschopoulos; Michail C Mitsis; Nikolaos Zakynthinakis-Kyriakou; Stergios Boussios; George Pappas-Gogos Journal: Ann Transl Med Date: 2020-12