| Title | Risk of pancreatic cancer in families with Lynch syndrome. | | Author(s) | Kastrinos F, Mukherjee B, Tayob N, Wang F, Sparr J, Raymond VM, Bandipalliam P, Stoffel EM, Gruber SB, Syngal S | | Institution | Department of Internal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. | | Source | JAMA 2009 Oct 28; 302(16):1790-5. | | MeSH | Adaptor Proteins, Signal Transducing
Adult
Aged
Aged, 80 and over
Colorectal Neoplasms, Hereditary Nonpolyposis
DNA Mismatch Repair
DNA Mutational Analysis
DNA-Binding Proteins
Female
Genotype
Germ-Line Mutation
Humans
Male
Middle Aged
MutS Homolog 2 Protein
Nuclear Proteins
Pancreatic Neoplasms
Pedigree
Phenotype
Proportional Hazards Models
Registries
Risk
SEER Program
Young Adult
| | Abstract | CONTEXT: Lynch syndrome is an inherited cause of colorectal cancer caused by mutations of DNA mismatch repair (MMR) genes. A number of extracolonic tumors have been associated with the disorder, including pancreatic cancer; however, the risk of pancreatic cancer in Lynch syndrome is uncertain and not quantified.
OBJECTIVE: To estimate pancreatic cancer risk in families with germline MMR gene mutations.
DESIGN, SETTING, AND PATIENTS: Cancer histories of probands and their relatives were evaluated in MMR gene mutation carriers in the familial cancer registries of the Dana-Farber Cancer Institute (n = 80), Boston, Massachusetts, and University of Michigan Comprehensive Cancer Center (n = 67), Ann Arbor, Michigan. Families enrolled before the study start date (June 2008) were eligible. Age-specific cumulative risks and hazard ratio estimates of pancreatic cancer risk were calculated and compared with the general population using modified segregation analysis, with correction for ascertainment.
MAIN OUTCOME MEASURES: Age-specific cumulative risks and hazard ratio estimates of pancreatic cancer risk.
RESULTS: Data on 6342 individuals from 147 families with MMR gene mutations were analyzed. Thirty-one families (21.1%) reported at least 1 case of pancreatic cancer. Forty-seven pancreatic cancers were reported (21 men and 26 women), with no sex-related difference in age of diagnosis (51.5 vs 56.5 years for men and women, respectively). The cumulative risk of pancreatic cancer in these families with gene mutations was 1.31% (95% confidence interval [CI], 0.31%-2.32%) up to age 50 years and 3.68% (95% CI, 1.45%-5.88%) up to age 70 years, which represents an 8.6-fold increase (95% CI, 4.7-15.7) compared with the general population.
CONCLUSIONS: Among 147 families with germline MMR gene mutations, the risk of pancreatic cancer was increased compared with the US population. Individuals with MMR gene mutations and a family history of pancreatic cancer are appropriate to include in studies to further define the risk of premalignant and malignant pancreatic neoplasms and potential benefits and limitations of surveillance. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
| | PubMed ID | 19861671 |
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