Case 7-2004: Hereditary Melanoma and Pancreatic Cancer
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《新英格兰医药杂志》
To the Editor: The discussants in Case 7-2004 (Feb. 26 issue)1 comprehensively review hereditary melanoma arising from inherited CDKN2A mutations, but they fail to mention the increased risk of pancreatic cancer associated with germ-line CDKN2A mutations.2,3 Although pancreatic cancer did not occur in the pedigree of the patient in this case, its absence could reflect the early death of affected family members. Carriers of germ-line CDKN2A mutations affecting the p16 protein have been estimated to have a 17 percent lifetime risk of pancreatic cancer.4 To help prevent premature death from pancreatic cancer, persons with an increased susceptibility to this cancer, such as those with a strong family history of the disease, can undergo pancreatic studies (including endoscopic ultrasonography and computed tomographic [CT] scanning) that can detect asymptomatic pancreatic neoplasms. Although the risks and benefits of this approach are the subject of ongoing studies, several clinical trials provide evidence that asymptomatic pancreatic neoplasms can be detected and treated by screening persons at high risk for pancreatic cancer.5,6 Whether this is also true of persons with germ-line CDKN2A mutations affecting p16 should be determined in prospective clinical trials.
Editor's note: Case 7-2004 was erroneously labeled Case 6-2004 in the print edition of the Journal.
Jens Koopmann, M.D.
Michael Goggins, M.D.
Ralph H. Hruban, M.D.
Johns Hopkins Medical Institutions
Baltimore, MD 21205
jkoopma1@jhmi.edu
References
Case Records of the Massachusetts General Hospital (Case 6-2004). N Engl J Med 2004;350:924-932.
Goldstein AM, Fraser MC, Struewing JP, et al. Increased risk of pancreatic cancer in melanoma-prone kindreds with p16INK4 mutations. N Engl J Med 1995;333:970-974.
Borg A, Sandberg T, Nilsson K, et al. High frequency of multiple melanomas and breast and pancreas carcinomas in CDKN2A mutation-positive melanoma families. J Natl Cancer Inst 2000;92:1260-1266.
Vasen HF, Gruis NA, Frants RR, van Der Velden PA, Hille ET, Bergman W. Risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma associated with a specific 19 deletion of p16 (p16-Leiden). Int J Cancer 2000;87:809-811.
Canto MI, Yeo CJ, Griffin C, et al. Screening for pancreatic neoplasia in high risk individuals. Clin Gastroenterol Hepatol (in press).
Brentnall TA, Bronner MP, Byrd DR, Haggitt RC, Kimmey MB. Early diagnosis and treatment of pancreatic dysplasia in patients with a family history of pancreatic cancer. Ann Intern Med 1999;131:247-255.
The discussants reply: We wish to thank Dr. Koopmann and colleagues for broaching the very important issue of the risk of pancreatic cancer in patients with CDKN2 mutations. This issue was discussed at the conference but not mentioned in the article because of space considerations. The patient indeed had full counseling regarding the risk of pancreatic cancer and was referred to a gastroenterologist for screening. Surveillance for pancreatic cancer is clearly an area of intense interest, given the high mortality associated with the disease. Although the collective goal of the medical community at large is to prevent premature death from pancreatic cancer, at the current time there is limited evidence to suggest that either endoscopic ultrasonography or CT scanning will alter survival. Thus, the prospective clinical trials proposed by Dr. Koopmann and associates will be essential to refine the sensitivity and specificity of screening strategies and to define the effect of these strategies on overall morbidity and mortality.
Hensin Tsao, M.D., Ph.D.
Arthur J. Sober, M.D.
Kristin B. Niendorf, M.S.
Massachusetts General Hospital
Boston, MA 02114
Editor's note: Case 7-2004 was erroneously labeled Case 6-2004 in the print edition of the Journal.
Jens Koopmann, M.D.
Michael Goggins, M.D.
Ralph H. Hruban, M.D.
Johns Hopkins Medical Institutions
Baltimore, MD 21205
jkoopma1@jhmi.edu
References
Case Records of the Massachusetts General Hospital (Case 6-2004). N Engl J Med 2004;350:924-932.
Goldstein AM, Fraser MC, Struewing JP, et al. Increased risk of pancreatic cancer in melanoma-prone kindreds with p16INK4 mutations. N Engl J Med 1995;333:970-974.
Borg A, Sandberg T, Nilsson K, et al. High frequency of multiple melanomas and breast and pancreas carcinomas in CDKN2A mutation-positive melanoma families. J Natl Cancer Inst 2000;92:1260-1266.
Vasen HF, Gruis NA, Frants RR, van Der Velden PA, Hille ET, Bergman W. Risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma associated with a specific 19 deletion of p16 (p16-Leiden). Int J Cancer 2000;87:809-811.
Canto MI, Yeo CJ, Griffin C, et al. Screening for pancreatic neoplasia in high risk individuals. Clin Gastroenterol Hepatol (in press).
Brentnall TA, Bronner MP, Byrd DR, Haggitt RC, Kimmey MB. Early diagnosis and treatment of pancreatic dysplasia in patients with a family history of pancreatic cancer. Ann Intern Med 1999;131:247-255.
The discussants reply: We wish to thank Dr. Koopmann and colleagues for broaching the very important issue of the risk of pancreatic cancer in patients with CDKN2 mutations. This issue was discussed at the conference but not mentioned in the article because of space considerations. The patient indeed had full counseling regarding the risk of pancreatic cancer and was referred to a gastroenterologist for screening. Surveillance for pancreatic cancer is clearly an area of intense interest, given the high mortality associated with the disease. Although the collective goal of the medical community at large is to prevent premature death from pancreatic cancer, at the current time there is limited evidence to suggest that either endoscopic ultrasonography or CT scanning will alter survival. Thus, the prospective clinical trials proposed by Dr. Koopmann and associates will be essential to refine the sensitivity and specificity of screening strategies and to define the effect of these strategies on overall morbidity and mortality.
Hensin Tsao, M.D., Ph.D.
Arthur J. Sober, M.D.
Kristin B. Niendorf, M.S.
Massachusetts General Hospital
Boston, MA 02114