| 21. |
- Wolpin, Brian M, et al.
(författare)
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Pancreatic cancer risk and ABO blood group alleles : results from the pancreatic cancer cohort consortium
- 2010
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 70:3, s. 1015-1023
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Tidskriftsartikel (refereegranskat)abstract
- A recent genome-wide association study (PanScan) identified significant associations at the ABO gene locus with risk of pancreatic cancer, but the influence of specific ABO genotypes remains unknown. We determined ABO genotypes (OO, AO, AA, AB, BO, and BB) in 1,534 cases and 1,583 controls from 12 prospective cohorts in PanScan, grouping participants by genotype-derived serologic blood type (O, A, AB, and B). Adjusted odds ratios (ORs) for pancreatic cancer by ABO alleles were calculated using logistic regression. Compared with blood type O, the ORs for pancreatic cancer in subjects with types A, AB, and B were 1.38 [95% confidence interval (95% CI), 1.18-1.62], 1.47 (95% CI, 1.07-2.02), and 1.53 (95% CI, 1.21-1.92), respectively. The incidence rates for blood types O, A, AB, and B were 28.9, 39.9, 41.8, and 44.5 cases per 100,000 subjects per year. An increase in risk was noted with the addition of each non-O allele. Compared with OO genotype, subjects with AO and AA genotype had ORs of 1.33 (95% CI, 1.13-1.58) and 1.61 (95% CI, 1.22-2.18), whereas subjects with BO and BB genotypes had ORs of 1.45 (95% CI, 1.14-1.85) and 2.42 (1.28-4.57). The population attributable fraction for non-O blood type was 19.5%. In a joint model with smoking, current smokers with non-O blood type had an adjusted OR of 2.68 (95% CI, 2.03-3.54) compared with nonsmokers of blood type O. We concluded that ABO genotypes were significantly associated with pancreatic cancer risk.
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| 22. |
- Wolpin, Brian M., et al.
(författare)
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Variant ABO Blood Group Alleles, Secretor Status, and Risk of Pancreatic Cancer: Results from the Pancreatic Cancer Cohort Consortium
- 2010
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Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755 .- 1055-9965. ; 19:12, s. 3140-3149
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Tidskriftsartikel (refereegranskat)abstract
- Background: Subjects with non-O ABO blood group alleles have increased risk of pancreatic cancer. Glycosyltransferase activity is greater for the A(1) versus A(2) variant, whereas O01 and O02 variants are nonfunctioning. We hypothesized: 1) A(1) allele would confer greater risk than A(2) allele, 2) protective effect of the O allele would be equivalent for O01 and O02 variants, 3) secretor phenotype would modify the association with risk. Methods: We determined ABO variants and secretor phenotype from single nucleotide polymorphisms in ABO and FUT2 genes in 1,533 cases and 1,582 controls from 12 prospective cohort studies. Adjusted odds ratios (OR) for pancreatic cancer were calculated using logistic regression. Results: An increased risk was observed in participants with A(1) but not A(2) alleles. Compared with subjects with genotype O/O, genotypes A(2)/O, A(2)/A(1), A(1)/O, and A(1)/A(1) had ORs of 0.96 (95% CI, 0.72-1.26), 1.46 (95% CI, 0.98-2.17), 1.48 (95% CI, 1.23-1.78), and 1.71 (95% CI, 1.18-2.47). Risk was similar for O01 and O02 variant O alleles. Compared with O01/O01, the ORs for each additional allele of O02, A(1), and A(2) were 1.00 (95% CI, 0.87-1.14), 1.38 (95% CI, 1.20-1.58), and 0.96 (95% CI, 0.77-1.20); P-value, O01 versus O02 = 0.94, A(1) versus A(2) = 0.004. Secretor phenotype was not an effect modifier (P-interaction = 0.63). Conclusions: Among participants in a large prospective cohort consortium, ABO allele subtypes corresponding to increased glycosyltransferase activity were associated with increased pancreatic cancer risk. Impact: These data support the hypothesis that ABO glycosyltransferase activity influences pancreatic cancer risk rather than actions of other nearby genes on chromosome 9q34. Cancer Epidemiol Biomarkers Prev; 19(12); 3140-9. (C) 2010 AACR.
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| 23. |
- Wu, Chen, et al.
(författare)
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Genome-wide association study of survival in patients with pancreatic adenocarcinoma
- 2014
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Ingår i: Gut. - : BMJ Publishing Group. - 0017-5749 .- 1468-3288. ; 63:1, s. 152-160
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVE: Survival of patients with pancreatic adenocarcinoma is limited and few prognostic factors are known. We conducted a two-stage genome-wide association study (GWAS) to identify germline variants associated with survival in patients with pancreatic adenocarcinoma. METHODS: We analysed overall survival in relation to single nucleotide polymorphisms (SNPs) among 1005 patients from two large GWAS datasets, PanScan I and ChinaPC. Cox proportional hazards regression was used in an additive genetic model with adjustment for age, sex, clinical stage and the top four principal components of population stratification. The first stage included 642 cases of European ancestry (PanScan), from which the top SNPs (p≤10(-5)) were advanced to a joint analysis with 363 additional patients from China (ChinaPC). RESULTS: In the first stage of cases of European descent, the top-ranked loci were at chromosomes 11p15.4, 18p11.21 and 1p36.13, tagged by rs12362504 (p=1.63×10(-7)), rs981621 (p=1.65×10(-7)) and rs16861827 (p=3.75×10(-7)), respectively. 131 SNPs with p≤10(-5) were advanced to a joint analysis with cases from the ChinaPC study. In the joint analysis, the top-ranked SNP was rs10500715 (minor allele frequency, 0.37; p=1.72×10(-7)) on chromosome 11p15.4, which is intronic to the SET binding factor 2 (SBF2) gene. The HR (95% CI) for death was 0.74 (0.66 to 0.84) in PanScan I, 0.79 (0.65 to 0.97) in ChinaPC and 0.76 (0.68 to 0.84) in the joint analysis. CONCLUSIONS: Germline genetic variation in the SBF2 locus was associated with overall survival in patients with pancreatic adenocarcinoma of European and Asian ancestry. This association should be investigated in additional large patient cohorts.
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| 24. |
- Zhang, Mingfeng, et al.
(författare)
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Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21
- 2016
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:41, s. 66328-66343
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10(-15)), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10(-9)) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10(-8)). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 (NR5A2), chr8q24.21 (MYC) and chr5p15.33 (CLPTM1L-TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal (n = 10) and tumor (n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10(-8)). This finding was validated in a second set of paired (n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10(-4)-2.0x10(-3)). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.
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