ABCMdb

PMID: 19885835

McWilliams RR, Petersen GM, Rabe KG, Holtegaard LM, Lynch PJ, Bishop MD, Highsmith WE Jr
Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and risk for pancreatic adenocarcinoma.
Cancer. 2010 Jan 1;116(1):203-9., 2010-01-01 [PubMed]

Sentences

No. Mutations Sentence Comment

55 ABCC7 p.Trp1282* Interestingly, 10% of carriers among cases carried W1282X compared with 1% of controls. Login to comment 56 ABCC7 p.Trp1282* This is a mutation overrepresented in the Ashkenazi Jewish population.19 However, of the 5 cases with W1282X mutations detected, only 2 reported Jewish heritage, and neither responded whether they were Ashkenazi. Login to comment 84 ABCC7 p.Arg347His ABCC7 p.Val520Phe (%) of Controls, n513,340 Significance Not detected 899 (94.7) 12,830 (96.2) OR, 1.40 (95% CI, 1.04-1.89) Detected 50 (5.3) 510 (3.8) P¼.027 DF508*,y 35 (70) 354 (69.4) R117H*,z 5 (10) 71 (13.9) G551D*,y 1 (2) 11 (2.2) N1303K*,y 1 (2) 8 (1.6) G542X*,y 8 (1.6) 1717-1G>A*,y 7 (1.4) 278915G>A* 6 (1.2) R553X*,y 6 (1.2) W1282X*,y 5 (10) 5 (1.0) R347H 5 (1.0) R1162X*,y 4 (0.8) 62111G>T*,y 4 (0.8) R560T*,y 3 (0.6) R347P* 1 (2) 2 (0.4) A455E* 2 (0.4) 3849110kbC>T* 2 (0.4) 394delTT 2 (0.4) G85E* 2 (0.4) 3905insTy 2 (0.4) 189811G>A* 2 (0.4) 2183AA>G 1 (0.2) 2184delA*,y 1 (0.2) 71111G>T*,y 1 (0.2) V520F 1 (0.2) S549Ry 1 (2) DI507*,y 1 (2) OR indicates odds ratio; CI, confidence interval. Login to comment 85 ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Ser549Asn ABCC7 p.Ser549Asn ABCC7 p.Tyr122* ABCC7 p.Met1101Lys ABCC7 p.Tyr1092* ABCC7 p.Ser1255* ABCC7 p.Phe508Cys ABCC7 p.Ala559Thr * Mutations recommended for screening by the American College of Medical Genetics.16 Mutations not listed but included in the 39-site assay: 3120þ1G>A, R334W, 3569delC, 1078delT, S549N, 3876delA, 1898þ5G>T, 2307insA, Y1092X, M1101K, S1255X, Y122X, A559T; in the 33-site assay: 3120þ1G>A, R334W, 3569delC, S549N, 3876delA, F508C. Login to comment 95 ABCC7 p.Phe1052Val ABCC7 p.Ser42Phe ABCC7 p.Ser912Leu ABCC7 p.Asn1088Ser S42F has been described in 1 Italian CF patient.25 E528E is a synonymous polymorphism involving the last base pair in exon 10 (1716 G > A), which has been reported to affect splicing, but has not been linked to severe pulmonary disease.26 S912L is thought to be a neutral variant (serine for a leucine), unless in cis position to another mutation.27 The F1052V missense mutation is a variant with a modest effect, with normal or near-normal sweat chloride tests in combination with other mild variants.28,29 N1088S is a novel mutation that substitutes asparagine for a serine amino acid, both positively charged, and its functionality is unclear. Login to comment 96 ABCC7 p.Met1191Ile The mutation M1191I is also novel, with a substitution of a hydrophobic amino acid for another (threonine for isoleucine). Login to comment 97 ABCC7 p.Ser1235Arg S1235R has been variably reported in CF patients, but phenotype is more severe in association with second cis mutations.30,31 The 5T poly-T polymorphism affects splicing of exon 932 and contributes to congenital bilateral absence of the vas deferens33 and possibly pancreatitis,4 but not pulmonary disease. It is difficult to determine whether there is an excess of compound heterozygotes detected (16%). Login to comment 103 ABCC7 p.Arg117His ABCC7 p.Ser1235Arg ABCC7 p.Phe1052Val ABCC7 p.Ser42Phe ABCC7 p.Ser912Leu ABCC7 p.Asn1088Ser ABCC7 p.Met1191Ile Compound Heterozygotes Among Pancreatic Cancer Cases CFTR Mutations Sex Age at Diagnosis, y Ever/Never Smoker Family History of Pancreatic Cancer Pancreatitis ‡3 Years Before Cancer Diagnosis df508/S42F M 70 Nonsmoker No No R117H/E528E (splice site) M 75 Smoker Yes No df508/S912L W 56 Smoker No No df508/N1088S W 73 Smoker No No df508/M1191I M 79 Smoker No No df508/S1235R M 73 Smoker No No df508/F1052V M 49 Smoker No No df508/5T M 60 Smoker No No Man indicates man; W, woman. Login to comment