2015年11月26日 星期四

胰臟癌會遺傳嗎?

Is pancreatic cancer hereditary?

Cancer of the pancreas is a genetic disease which means that it is caused by changes (mutations) in DNA. These changes can be inherited (we are born with them) or they can be acquired (they develop after we are born). The inherited changes explain why cancer of the pancreas runs in some families, and the acquired changes can be the result of either bad luck during cell replication or by exposure to carcinogens (cancer causing chemicals) such as those found in cigarette smoke. The genetics of hereditary pancreatic cancer is a focus of research at Johns Hopkins.
It has been estimated that ten percent of pancreatic cancers are hereditary. Many of these occur as part of rare medical syndromes. These include:
  1. Familial breast cancer gene(BRCA2)
    BRCA2 was the second familial breast cancer gene identified. It was discovered in 1995 because of a remarkable advance made by the Hopkins team studying pancreatic cancer. The team at Hopkins had discovered a "homozygous deletion" (a missing piece of DNA) in a pancreatic cancer and postulated that this missing piece of DNA is where the BRCA2 gene could be found (Schutte et al, Proceedings of the National Academy of Sciences, 1995). Subsequently, Dr. Goggins at Hopkins demonstrated that as many as 10% of pancreas cancers are caused by inherited defects in the BRCA2 gene. One particular defect in BRCA2 (a mutation called 6174 del T) is found in about 1% of individuals of Ashkenazi Jewish descent. This mutation may explain the higher rate of pancreatic cancer observed in Jews as compared to Catholics and Protestants. Testing is now available for BRCA2 gene mutations. We advise that people speak with a trained cancer genetics counselor before undergoing genetic testing.
  2. More recently, the team at Johns Hopkins discovered that inherited mutations in PALB2 (partner and localizer of BRCA2), a gene that functions together with BRCA2, cause about 3% of familial pancreatic cancer, and other groups have found that inherited mutations in the first breast cancer gene, BRCA1, may also increase the risk of pancreatic cancer. Testing is also available for BRCA1 and PALB2 gene mutations. We advise that people speak with a trained cancer genetics counselor before undergoing genetic testing.
  3. Peutz-Jeghers syndrome
    This is a very rare hereditary syndrome in which affected family members develop polyps in their small intestines and pigmented spots on their lips and inside of their mouth. These polyps are masses of tissue that protrude from the normal surface of the intestine. Peutz-Jeghers is caused by inherited mutations in the STK11gene. Patients with Peutz-Jeghers syndrome have an increased risk of developing pancreas cancer.
    Peutz-Jeghers syndrome
  4. Familial melanoma
    The Familial Atypical Multiple Mole Melanoma (FAMMM) syndrome is a rare hereditary syndrome in which affected family members develop skin moles and melanomas (an aggressive form of skin cancer). These patients also have an increased risk of developing pancreas cancer. FAMMM is caused by inherited mutations in the p16/CDKN2A gene.
  5. Hereditary colon cancer
    The Hereditary Non-polyposis Colorectal Cancer (HNPCC) syndrome, also known as Lynch syndrome, strikes as many as 1 in 200 individuals and it is characterized by the inherited predisposition to develop colon cancer, endometrial (uterine) cancer, stomach cancer and ovarian cancer. Patients with HNPCC may also have an increased risk of developing pancreas cancer. Indeed, the DNA finding typical of HNPCC, called microsatellite instability has recently been reported in a small (about 4%) fraction of pancreas cancers. Gene testing for HNPCC is now available.
  6. Hereditary pancreatitis
    This rare disease is characterized by the development of recurrent episodes of severe chronic pancreatitis (inflammation of the pancreas) starting at an early age (often in patients in their teens). The gene responsible for hereditary pancreatitis, called the trypsinogen gene, was discovered by Dr. Whitcomb of the University of Pittsburgh. Clinical gene testing for hereditary pancreatitis is now available.
  7. Ataxia telangiectasia
    The team at Johns Hopkins discovered that inherited mutations in the ATM gene also increase the risk of pancreatic cancer. Inherited mutations in ATM are known to cause the clinical syndrome of "ataxia telangiectasia," and 2-3% of people with familial pancreatic cancer inherited a defective (mutant) copy of theATM gene.
  8. Familial pancreatic cancer
    While the above genetic syndromes account for ~20% of familial pancreatic cancer, it is clear that there are other, yet undiscovered familial pancreatic cancer genes. For example, relatives of patients with pancreas cancer have an increased risk for developing pancreas cancer themselves, and the National Familial Pancreas Cancer Registry now contains over 1500 families in which two or more family members have had pancreas cancer.
    Scientists at Johns Hopkins are working diligently to discover the reasons why pancreas cancer runs in these families. Anyone wishing to join this registry or wishing to learn more about familial pancreas cancer may contact Alison Klein at aklein1@jhmi.edu.

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