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Comment & Response
February 28, 2019

CHEK2 Alleles Predispose to Renal Cancer in Poland

Author Affiliations
  • 1Department of Genetics, Pomeranian Medical University, Szczecin, Poland
  • 2Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada
  • 3Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
JAMA Oncol. 2019;5(4):576. doi:10.1001/jamaoncol.2019.0022

Carlo et al1 reported that CHEK2 mutations were the most common inherited mutations found in 254 unselected patients with advanced renal cancer in the United States. In 2004, we reported that the CHEK2 missense mutation I157T was associated with a 2-fold increased risk of renal cancer in Poland.2 To extend our earlier findings, we have begun a new study of CHEK2 mutations. Thus far, we have genotyped 835 patients with invasive renal cancer (including 264 included in the prior study2) and 8302 cancer-free, population-based, adult control participants for 4 CHEK2 founder alleles: 1 missense mutation (I157T) and 3 truncating mutations (1100delC, IVS2 + 1G>A, del5395). The I157T allele was present in 78 participants with renal cancer and 410 control participants (odds ratio [OR], 2.0; 95% CI, 1.6-2.6; P < .001) (unpublished data, 2018). A truncating mutation was present in 20 participants and 80 control participants (OR, 2.5; 95% CI, 1.5-4.1; P = .0003) (unpublished data, 2018). Unlike the situation for breast cancer,3 but similar to the situation for colon cancer,4 the risk of cancer associated with the missense allele was similar to that of the truncating alleles. In Poland, the number of I157T mutations in patients with renal cancer outnumbered the 1100delC mutations by 193 to 4 (unpublished data, 2018), whereas in the United States, the 1100delC alleles outnumbered the I157T alleles by 7 to 2.1 The lifetime risk of renal cancer in Poland is 1% (Polish Cancer Registry) and even if the risk is doubled, we do not believe that the risk is sufficiently high to warrant ultrasound screening of CHEK2 carriers.

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