Impact of Sixteen Established Pancreatic Cancer Susceptibility Loci in American Jews

Abstract

Background The higher risk of pancreatic cancer in Ashkenazi Jews compared to non-Jews is only partially explained by the increased frequency of BRCA1 and BRCA2 mutations in Ashkenazi Jews. Methods We evaluated the impact of 16 established pancreatic cancer susceptibility loci in a case-control sample of American Jews, largely Ashkenazi, including 406 full-Jewish pancreatic cancer patients and 2,332 full-Jewish controls, genotyped as part of the Pancreatic Cancer Cohort and Case-Control Consortium I/II (PanScan I/II), Pancreatic Cancer Case-Control Consortium (PanC4), and Resource for Genetic Epidemiology Research on Adult Health and Aging (GERA) data sets. We compared risk in full-Jewish subjects to risk in part-Jewish, non-Jewish Southern European, and in the combined non-Jewish Eastern, Northern, Southern, and Western European (non-Jewish white-European) subjects from the same data sets. Jewish ancestries were genetically identified using seeded Fast principal component analysis. Data were analyzed by unconditional logistic regression, and adjusted for age, sex, and principal components (PCs). Results One SNP on chromosome 13q22.1 (rs9543325, OR=1.36, 95% CI=1.16–1.58, P=10−4.1) was significant in full-Jews. Individual ORs and minor allele frequencies were similar between Jewish and non-Jewish white-European subjects. The average ORs across the 16 pancreatic cancer susceptibility loci for full-Jewish, full- plus part-Jewish, non-Jewish Southern European, and non-Jewish white-European subjects were 1.25, 1.30, 1.31, and 1.26, respectively. Conclusion The 16 pancreatic cancer susceptibility loci similarly impact Jewish and non-Jewish white-European subjects, both individually and as summary odds. Impact These 16 pancreatic cancer susceptibility loci likely do not explain the higher risk seen in Ashkenazi Jews.

Susceptibility loci for pancreatic cancer in the Brazilian population

“…In PA, this value increased to 56% and was associated with increased risk for pancreatic cancer in all models analyzed. This association was previously showed in Europeans [ 28 , 39 ], including Jewish and non-Jewish [ 40 ], and in the Taiwanese population [ 41 ]. This intergenic SNP maps at 13q22.1 locus, and has been showed to be strongly associated with pancreatic cancer [ 1 , 3 , 36 , 40 – 42 ].…”

Susceptibility Loci for Pancreatic Cancer in the Brazilian Population

“…This association was previously showed in Europeans [17,40], including Jewish and non-Jewish [41], and in the Taiwanese population [42]. This intergenic SNP maps at 13q22.1 locus, and has been showed to be strongly associated with pancreatic cancer [1,3,37,[41][42][43]. The locus 13q22.1 has other SNPs associated previously with PA, mainly in European and Chinese populations, some studies suggest a potential long-range enhancer activity but mechanisms are still unknown [44].…”

“…In PA, this value increased to 56% and was associated with increased risk for pancreatic cancer in all models analyzed. This association was previously showed in Europeans [17,40], including Jewish and non-Jewish [41], and in the Taiwanese population [42]. This intergenic SNP maps at 13q22.1 locus, and has been showed to be strongly associated with pancreatic cancer [1,3,37,[41][42][43].…”

A study of Kibbutzim in Israel reveals risk factors for cardiometabolic traits and subtle population structure

“…While no functional enriched variants were observed in BRCA1 or BRCA2 in the KFS, a number of genes with functional enriched variants were found to interact with BRCA1 (Supplementary Table 8). We note that whether cancer is more prevalent in Ashkenazi Jews compared to the general Western population is debated, and possibly limited to colorectal and prostate cancers, if at all [54][55][56].…”