Germline variants in the APC and MUTYH genes contribute to colorectal cancer (CRC) and adenoma risk, though may occur with varying frequencies in individuals of different ancestries. The aim of this study was to evaluate the prevalence of APC, monoallelic MUTYH and biallelic MUTYH germline variants in Ashkenazi Jewish (AJ) and Other Ancestry (OA) individuals with colorectal adenomas. We studied 7225 individuals with colorectal adenomas who had germline APC and MUTYH testing at a commercial laboratory. Cross-sectional medical history data were extracted from provider-completed test requisition forms. We performed bivariate analysis to compare the frequency of APC and MUTYH variants between AJ and OA, and examined APC p.I1307K and monoallelic MUTYH carrier phenotypes using logistic regression. Pathogenic APC variants occurred in 38/285 AJ (13%) and 1342/6940 OA (19%; P = 0.09); biallelic MUTYH variants in 2/285 (1%) AJ and 399/6940 (6%) OA (P < 0.0001); APC p.I1307K in 35/285 (12%) AJ and 29/6940 (1%) OA (P < 0.0001); and monoallelic MUTYH in 2/285 (1%) AJ and 133/6940 (2%) OA (P = 0.06). Monoallelic MUTYH variants were significantly associated with having a personal history of CRC, regardless of ancestry (OR 1.78; 95% CI 1.21–2.49; P < 0.01), but no significant association was found between APC p.I1307K variants and personal history of CRC (OR 1.38; 95% CI 0.79–2.44; P = 0.26). Ashkenazim with colorectal adenomas rarely have monoallelic or biallelic MUTYH variants, suggesting different genetic etiologies for polyposis in AJ compared to OA individuals. AJ ancestry assessment may be important in clinical evaluation for polyposis.

APC和MUTYH基因中的种系变异会导致结直肠癌 (CRC) 和腺瘤风险，尽管在不同血统的个体中可能以不同的频率发生。本研究的目的是评估APC、单等位基因MUTYH和双等位基因MUTYH种系变异在德系犹太人 (AJ) 和其他祖先 (OA) 结直肠腺瘤患者中的患病率。我们研究了 7225 名患有生殖系APC和MUTYH的结直肠腺瘤患者在商业实验室进行测试。从提供者完成的测试申请表中提取横断面病史数据。我们进行了双变量分析以比较AJ 和 OA 之间APC和MUTYH变体的频率，并使用逻辑回归检查了APC p.I1307K 和单等位基因MUTYH携带者表型。致病性APC变异发生在 38/285 AJ (13%) 和 1342/6940 OA (19%; P  = 0.09)；2/285 (1%) AJ 和 399/6940 (6%) OA 中的双等位基因MUTYH变体 ( P  < 0.0001)；APC p.I1307K 在 35/285 (12%) AJ 和 29/6940 (1%) OA ( P  < 0.0001)；和单等位基因MUTYH在 2/285 (1%) AJ 和 133/6940 (2%) OA ( P  = 0.06)。单等位基因MUTYH变体与个人 CRC 病史显着相关，无论其血统如何（OR 1.78；95% CI 1.21–2.49；P < 0.01），但在APC p.I1307K 变体与个人 CRC 病史 之间未发现显着关联（OR 1.38；95% CI 0.79–2.44；P  = 0.26）。患有结直肠腺瘤的 Ashkenazim 很少有单等位基因或双等位基因MUTYH变体，这表明与 OA 个体相比，AJ 中息肉病的遗传病因不同。AJ 血统评估在息肉病的临床评估中可能很重要。