Ashkenazi Jewish and Other White <i>APC</i> I1307K Carriers Are at Higher Risk for Multiple Cancers

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 p p p p p 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