Supplementary Table 1: Previous reports relevant to Early Onset Pancreatic Cancer (EOPC).

Transcription

1 Supplementary Table 1: Previous reports relevant to Early Onset Pancreatic Cancer (EOPC). First author (year) Environmental and genetic factors Maximum age of EOPC group Number of EOPC cases Total number of pancreas cancer cases Main findings Soliman AS (2002) (1) Environment About 25% EOPC in East Nile Delta Region of Egypt Kriegel AM (2006) (2) Cadmium /3 of PC patients with high serum cadmium levels were <60 at diagnosis (East Nile area of Egypt) Zisman A (2005) (3) Smoking Not stated Not stated 18,872 Age at onset of PC=64 for current smokers, 74 for non smokers (p<0.001) Olson SH (2006) (4) Smoking Smoking and obesity more present in early onset PC Lowenfels AB (2001) (5)* Hereditary pancreatitis, smoking Median age at onset of PC: 50 in smokers, 70 in non-smokers (p=0.02) Bergmann F (2006) (6) K-RAS Only 42% (n=3) patients carried a mutation in K- RAS, while 90-95% were expected for common pancreatic ductal adenocarcinoma Van der Heijden MS (2003) (7) Couch FJ (2005) (8) Fanconi anemia gene mutation Fanconi anemia gene mutation tumors 11 cell lines Mutation identified in 4 PC cases with mean age at onset 48. Among 9 PC cases diagnosed before age 50, 3 carried the mutation 55 Not stated 421 FANCC mutation identified in 2 PC cases with age onset 40 and 55 and no family history of PC

2 Borg A (2000) (9) Vasen HFA (2000) (10) Ghiorzo P (2004) (11) Chen J (2007) (12) and personal communication Lim W (2004) (13) Birch JM (2001) (14) and personal communication FAMMM FAMMM FAMMM women Standardized Mortality Rate for PC was 39 for all the CDKN2A female carriers, 65 for CDKN2A female carriers aged < Mean age PC=59. 30%<50 years Not stated 3 19 A higher proportion of early cancer of any type was found in first degree relatives of EOPC patients compared to relatives of late onset pancreas cancer patients (4/6 vs 2/22, p<0.05) Aurora-A, p Median age at diagnosis of PC: 59.6 in Aurora-A variant carriers, 62.4 in Aurora-A wild-type (p=0.015); 50.8 in patients with variants both in Aurora-A and p16, 63.4 in Aurora-A and p16 wild-type subjects (p=0.0002). Peutz-Jeghers Li-Fraumeni families (P53) Out of 240 patients: 6 PC, all diagnosed between 34 and 49 years Not stated Not stated 6 PC in 6 patients with TP53 mutation, median age at onset 45 yrs Nichols KE (2001) (15) P53, familial PC PC case aged 49 carried p53 mutation, 2 PC cases aged 36 and 49 had familial PC Masamune A (2007) (16) and personal communication SPINK out of 11 patients with N34S variant and chronic pancreatitis had PC with age at onset 44, 64 and 73. No SPINK1 wild-type subjects developed PC Hucl T (2007) (17) SPINK A case report of a 42-year-old woman with PC and N34S mutation Schenk M (2001) (18) * Familial pancreatic cancer, smoking Significant high risk of PC for smokers if proband had PC<60 (RR=8.23, 95%CI )

3 Klein AP (2004) (19) James TA (2004) (20) * Familial pancreatic cancer Familial pancreatic cancer, smoking Elevated PC risk in age group (SIR=15.8, 05%CI ) (11 familial, 146 sporadic) 826 (30 familial, 796 sporadic) 37% EOPC in familial PC, 18% in sporadic PC (p=0.017). Smoking more common with early onset PC Eberle M (2002) (21) PALLD Not stated Not stated cases of PC in family X, with median age at onset 43 Rulyak SJ (2003) (22) * PALLD, smoking Smoking advances the age of onset of PC by 10 years Zogopoulous G (2007) (23) Maisonneuve P (2007) (24) Mc Williams R (2005) (25) Hemminki K (2003) (26)* Shen M (2006) (27) PALLD No EOPC case had P239S PALLD variant. Only one P239S PALLD variant was observed among 84 PC cases (age at onset 74) Cystic Fibrosis PC cases, median age at onset 35 CFTR mutation CFTR mutations identified in 2 of 7 PC cases <60 (at age 42 and 50), but in 0 of 26 PC cases >60 Family history of any cancer Second primary cancer 50 Not stated 21,183 SIR for PC was 4.40 (95%CI ) among offspring diagnosed before age 50 when parents had lung cancer before age ,460 (14,087 first primary, 373 second primary) 112,831 (105,771 first primary, 7060 second primary) Elevated risk of PC after several types of tumors especially in young patients Basso D (2007) (28) XRCC XRCC1 194Trp allele frequency significantly higher (p<0.05) in PC than chronic pancreatitis cases only in subjects <60 years old. 5/19 EOPC were XRCC1 Arg194Trp, while 0/20 patients with early onset chronic pancreatitis had XRCC1

4 Phelan CM (1996) (29) BRCA1,BRCA in breast cancer families 194Trp mutation. Average age at PC onset in BRCA2 carriers: 53, significantly lower than expected in Canadian population (p=0.013) Hahn SA (2003) (30) BRCA1,BRCA % of PC cases diagnosed before age 50. Two cases of both pancreatic and breast carcinoma (13%) in 16 members of one family. Role of BRCA2 suggested Bermejo JL (2004) (31) BRCA1,BRCA Families with 2 early onset breast cancer have a 5-6 fold increased risk of young onset PC Lynch HT (2005) (32) BRCA1,BRCA Out of 9 BRCA1 families, 3 PC cases were diagnosed at 47, 50, and 51 years. Average age at PC onset=65 in BRCA1 carriers, 52.5 in BRCA2 carriers Mellemkjaer L (2006) (33) BRCA1,BRCA2 Not stated Not stated 1215 Increased risk of PC after early onset breast cancer (SIR=1.75, 95%CI ) Couch FJ (2007) (34) BRCA1,BRCA EOPC probands 151 pancreas cancer families PC= Pancreas cancer; EOPC=Early onset pancreas cancer; SIR=Standardized Incidence Ratio; RR=Relative Risk * Evidence for smoking interaction ^ from graphical presentation 4/5 families with BRCA2 mutations were identified through probands with early onset (<55) PC. 8/10 families carrying BRCA2 mutations presented at least one early onset PC

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7 25. McWilliams R, Highsmith WE, Rabe KG, et al. Cystic fibrosis transmembrane regulator gene carrier status is a risk factor for young onset pancreatic adenocarcinoma. Gut 2005;54: Hemminki K, Li X. Familial and second primary pancreatic cancers: a nationwide epidemiologic study from Sweden. Int J Cancer 2003;103: Shen M, Boffetta P, Olsen JH, et al. A pooled analysis of second primary pancreatic cancer. Am J Epidemiol 2006;163: Basso D, Navaglia F, Fogar P, et al. DNA repair pathways and mitochondrial DNA mutations in gastrointestinal carcinogenesis. Clin Chim Acta 2007;381: Phelan CM, Lancaster JM, Tonin P, et al. Mutation analysis of the BRCA2 gene in 49 site-specific breast cancer families. Nat Genet 1996;13: Hahn SA, Greenhalf B, Ellis I, et al. BRCA2 germline mutations in familial pancreatic carcinoma. J Natl Cancer Inst 2003;95: Lorenzo BJ, Hemminki K. Risk of cancer at sites other than the breast in Swedish families eligible for BRCA1 or BRCA2 mutation testing. Ann Oncol 2004;15: Lynch HT, Deters CA, Snyder CL, et al. BRCA1 and pancreatic cancer: pedigree findings and their causal relationships. Cancer Genet Cytogenet 2005;158: Mellemkjaer L, Friis S, Olsen JH, et al. Risk of second cancer among women with breast cancer. Int J Cancer 2006;118: Couch FJ, Johnson MR, Rabe KG, et al. The prevalence of BRCA2 mutations in familial pancreatic cancer. Cancer Epidemiol Biomarkers Prev 2007;16:342-6.