多原发恶性肿瘤的病因和发病机制的探讨_West China Medical Journal

Authors：

 李红梅 ,  李平

四川大学华西医院肿瘤中心头颈- 乳腺肿瘤科（成都 610041）;

Corresponding author：

李平, Email: leepingmd68@163.com

Keywords：

多原发恶性肿瘤; 病因; 发病机制; 治疗

DOI：

10.7507/1002-0179.201600267

Video：

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Abstract Full text Figures/Tables Video References Cited by

多原发恶性肿瘤是肿瘤发生学上一种少见的现象。但近年来，随着诊疗技术的进步，肿瘤患者的5年生存率普遍提高。基于人群的研究结果提示伴随着生存期的延长，患者发生第二肿瘤的概率也逐渐提高。因此，关于多原发恶性肿瘤的报道越来越多。现通过复习国内外的历年有关报道，主要探讨多原发癌的病因和发病机制，以加深医务人员对多原发恶性肿瘤的认识。

Citation： 李红梅, 李平. 多原发恶性肿瘤的病因和发病机制的探讨. West China Medical Journal, 2016, 31(5): 991-995. doi: 10.7507/1002-0179.201600267 Copy

1.	Billroth T. Die allgemeine chirurgische pathologie und therapie: in funfzig vorlesungen: ein handbuch fur studirende und arzte[M]. 14th ed. Burlin: Auflage, 1889.
2.	Pietrysiak A, Konieczny P. Multiple primary malignant neoplasms[J]. Otolaryngol Pol, 1995, 49(Suppl 20): 187-190.
3.	石莉, 周树林, 姜旖, 等. 妇科恶性肿瘤相关的多发性原发性恶性肿瘤30例临床分析[J]. 中华妇产科杂志, 2014, 49(3): 199-203.
4.	王成锋, 赵平, 白晓枫, 等. 乳腺癌合并多原发恶性肿瘤的临床特点[J]. 中华医学杂志, 2002, 82(18): 1229-1231.
5.	Lee J, Park S, Kim S, et al. Characteristics and survival of breast cancer patients with multiple synchronous or metachronous primary cancers[J]. Yonsei Med J, 2015, 56(5): 1213-1220.
6.	Jhavar S, Sarin R, Mulherkar R, et al. Glutathione S-transferase M1 or T1 null genotype as a risk factor for developing multiple primary neoplasms in the upper aero-digestive tract, in Indian males using tobacco[J]. Oral Oncol, 2004, 40(1): 84-91.
7.	Ukhanov AP, Zakharov DV. Primary-multiple synchronous cancer of the stomach and colon in elderly patients[J]. Vestn Khir Im II Grek, 2005, 164(2): 80-81.
8.	朱义荣. 多原发癌[J]. 医学理论与实践, 2006, 19(11): 1249-1250.
9.	王成峰, 邵永孚, 张海增, 等. 多原发恶性肿瘤[J]. 中国肿瘤临床, 2000, 27(6): 439-442.
10.	Ueno M, Muto T, Oya M, et al. Multiple primary cancer: an experience at the Cancer Institute Hospital with special reference to colorectal cancer[J]. Int J Clin Oncol, 2003, 8(3): 162-167.
11.	Beisland C, Talleraas O, Bakke A, et al. Multiple primary malignancies in patients with renal cell carcinoma: a national population-based cohort study[J]. BJU Int, 2006, 97(4): 698-702.
12.	Mariotto AB, Rowland JH, Ries LA, et al. Multiple cancer prevalence: a growing challenge in long-term survivorship[J]. Cancer Epidemiol Biomarkers Prev, 2007, 16(3): 566-571.
13.	Xu H, Zhang M, Zhai G, et al. The clinical significance of 18F-FDGPET/ CT in early detection of second primary malignancy in cancer patients[J]. J Cancer Res Clin Oncol, 2010, 136(8): 1125-1134.
14.	Mercer RR, Lucas NC, Simmons AN, et al. Molecular discrimination of multiple primary versus metastatic squamous cell cancers of the head/neck and lung[J]. Exp Mol Pathol, 2009, 86(1): 1-9.
15.	Mhawech-Fauceglia P, Rai H, Nowak N, et al. The use of arraybased comparative genomic hybridization (a-CGH) to distinguish metastatic from primary synchronous carcinomas of the ovary and the uterus[J]. Histopathology, 2008, 53(4): 490-495.
16.	任静, 李学. 多原发癌(六重癌)1例[J]. 中日友好医院学报, 2010, 24(2): 123-124.
17.	Moertel CG, Dockerty MB, Baggenstoss AH. Multiple primary malignant neoplasms. Ii. Tumors of different tissues or organs[J]. Cancer, 1961(14): 231-237.
18.	Irimie A, Achimas-Cadariu P, Burz C, et al. Multiple primary malignancies--epidemiological analysis at a single tertiary institution[J]. J Gastrointestin Liver Dis, 2010, 19(1): 69-73.
19.	Gursel B, Meydan D, Özbek N, et al. Multiple primary malignant neoplasms from the Black Sea region of Turkey[J]. J Int Med Res, 2011, 39(2): 667-674.
20.	Giardiello C, Angelone G, Iodice G, et al. Diagnosis, therapy, and follow up in synchronous colorectal cancer of the colon][J]. Il Giornale Di Chirurgia, 2001, 22(4): 122-124.
21.	钟海鸣, 陈景胜, 吴昱冶, 等. 多原发癌86例临床分析[J]. 广东医学院学报, 2009, 27(4): 433-434.
22.	Luciani A, Balducci L. Multiple primary malignancies[J]. Semin Oncol, 2004, 31(2): 264-273.
23.	Simpkins F, Zahurak M, Armstrong D, et al. Ovarian malignancy in breast cancer patients with an adnexal mass[J]. Obstet Gynecol, 2005, 105(3): 507-513.
24.	Cybulski C, Nazarali S, Narod SA. Multiple primary cancers as a guide to heritability[J]. Int J Cancer, 2014, 135(8): 1756-1763.
25.	Watson P, Vasen HF, Mecklin JP, et al. The risk of endometrial cancer in hereditary nonpolyposis colorectal cancer[J]. Am J Med, 1994, 96(6): 516-520.
26.	Utada M, Ohno Y, Hori M, et al. Incidence of multiple primary cancers and interval between first and second primary cancers[J]. Cancer Sci, 2014, 105(7): 890-896.
27.	Talbott VA, Yeo CJ, Brody JR, et al. Molecular profiling of synchronous and metachronous cancers of the pancreas reveal molecular mimicry between samples from the same patient[J]. J Surg Res, 2012, 176(1): 154-158.
28.	任延律, 张岂凡, 于志伟, 等. 大肠重复癌微卫星不稳定性研究[J]. 肿瘤防治研究, 2003, 30(5): 354-356.
29.	王科明, 胡雪珍, 王朝霞, 等. 双原发癌的随访及细胞免疫功能变化[J]. 临床内科杂志, 1998, 15(5): 273-274.
30.	Barroso-Vicens E, Ramirez G, Rabb H. Multiple primary malignancies in a renal transplant patient[J]. Transplantation, 1996, 61(11): 1655-1656.
31.	Hashibe M, Ritz B, Le AD, et al. Radiotherapy for oral cancer as a risk factor for second primary cancers[J]. Cancer Lett, 2005, 220(2): 185-195.
32.	田雨霖, 佟玉兰, 何三光, 等. 胰癌、食管癌、胃癌三重复癌1例 [J]. 实用外科杂志, 1990, 10(5): 238.
33.	Narod SA, Brunet JS, Ghadirian P, et al. Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a case-control study[J]. Lancet, 2000, 356(9245): 1876-1881.
34.	Narod SA, Pal T, Graham T, et al. Tamoxifen and risk of endometrial cancer[J]. Lancet, 2001, 357(9249): 65-66.
35.	Angurana SL, Kapoor R, Kumar P, et al. Quadruple malignancy in a single patient: a case report and comprehensive review of literature[J]. J Cancer Res Ther, 2010, 6(2): 230-232.
36.	Nakashima M, Kondo H, Miura S, et al. Incidence of multiple primary cancers in Nagasaki atomic bomb survivors: association with radiation exposure[J]. Cancer Sci, 2008, 99(1): 87-92.
37.	Braisch U, Meyer M, Radespiel-Tröger M. Risk of tobacco-related multiple primary cancers in Bavaria, Germany[J]. BMC Cancer, 2012, 12: 250.
38.	Shiels MS, Gibson T, Sampson J, et al. Cigarette smoking prior to first cancer and risk of second smoking-associated cancers among survivors of bladder, kidney, head and neck, and stage I lung cancers[J]. J Clin Oncol, 2014, 32(35): 3989-3995.
39.	Gibson TM, Park Y, Robien K, et al. Body mass index and risk of second obesity-associated cancers after colorectal cancer: a pooled analysis of prospective cohort studies[J]. J Clin Oncol, 2014, 32(35): 4004-4011.
40.	Bukhtoyarov OV, Samarin DM. Psychogenic carcinogenesis: carcinogenesis is without exogenic carcinogens[J]. Med Hypotheses, 2009, 73(4): 531-536.
41.	Gonzalez MJ, Massari JR, Duconge J, et al. The bio-energetic theory of carcinogenesis[J]. Med Hypotheses, 2012, 79(4): 433-439.
42.	Anderson MR. Variations in the rate of induction of chemical carcinogenesis according to differing psychological states in rats[J]. Nature, 1964, 204: 55-56.
43.	Slaughter DP, Southwick HW, Smejkal W. Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin[J]. Cancer, 1953, 6(5): 963-968.
44.	Heroiu CA, Danciu CE, Popescu CR. Multiple cancers of the head and neck[J]. Maedica (Buchar), 2013, 8(1): 80-85.
45.	Bedi GC, Westra WH, Gabrielson E, et al. Multiple head and neck tumors: evidence for a common clonal origin[J]. Cancer Res, 1996, 56(11): 2484-2487.
46.	Garrean S, Hering J, Saied A, et al. Gastric adenocarcinoma arising from fundic gland polyps in a patient with familial adenomatous polyposis syndrome[J]. Am Surg, 2008, 74(1): 79-83.
47.	Hamm A, Veeck J, Bektas N, et al. Frequent expression loss of Interalpha- trypsin inhibitor heavy chain (ITIH) genes in multiple human solid tumors: a systematic expression analysis[J]. BMC Cancer, 2008(8): 25.
48.	Shen C, Wang X, Tian L, et al. Microsatellite alteration in multiple primary lung cancer[J]. J Thorac Dis, 2014, 6(10): 1499-1505.
49.	李刚, 吴德昌. 肿瘤相关基因突变是辐射致癌的主要分子事件[J]. 中华放射医学与防护杂志, 1998, 18(3): 214.
50.	Sudo H, Garbe J, Stampfer MR, et al. Karyotypic instability and centrosome aberrations in the progeny of finite life-span human mammary epithelial cells exposed to sparsely or densely ionizing radiation[J]. Radiat Res, 2008, 170(1): 23-32.
51.	陈燕青, 周川, 王家东. 头颈部多原发癌[J]. 临床耳鼻咽喉科杂志, 2004, 18(9): 574-576.
52.	徐启明, 孙玉鹗, 刘颖, 等. 肺癌患者的多原发恶性肿瘤[J]. 中国肿瘤临床, 2000, 27(7): 498-501.
53.	王军英, 涂彧, 周菊英. 异时性三原发癌1例[J]. 临床肿瘤学杂志, 2007, 12(9): 720.
54.	王婧, 李琴, 赵志海, 等. 多原发恶性肿瘤的诊疗进展[J]. 医学综述, 2011, 17(10): 1490-1492.
55.	Jégu J, Colonna M, Daubisse-Marliac L, et al. The effect of patient characteristics on second primary cancer risk in France[J]. BMC Cancer, 2014, 14: 94.
56.	张世馥, 汪万英, 曹光群, 等. 多原发恶性肿瘤的病理诊断和免疫组织化学研究[J]. 中国肿瘤临床, 1991, 18(5): 347-349, 385.

1. Billroth T. Die allgemeine chirurgische pathologie und therapie: in funfzig vorlesungen: ein handbuch fur studirende und arzte[M]. 14th ed. Burlin: Auflage, 1889.
2. Pietrysiak A, Konieczny P. Multiple primary malignant neoplasms[J]. Otolaryngol Pol, 1995, 49(Suppl 20): 187-190.
3. 石莉, 周树林, 姜旖, 等. 妇科恶性肿瘤相关的多发性原发性恶性肿瘤30例临床分析[J]. 中华妇产科杂志, 2014, 49(3): 199-203.
4. 王成锋, 赵平, 白晓枫, 等. 乳腺癌合并多原发恶性肿瘤的临床特点[J]. 中华医学杂志, 2002, 82(18): 1229-1231.
5. Lee J, Park S, Kim S, et al. Characteristics and survival of breast cancer patients with multiple synchronous or metachronous primary cancers[J]. Yonsei Med J, 2015, 56(5): 1213-1220.
6. Jhavar S, Sarin R, Mulherkar R, et al. Glutathione S-transferase M1 or T1 null genotype as a risk factor for developing multiple primary neoplasms in the upper aero-digestive tract, in Indian males using tobacco[J]. Oral Oncol, 2004, 40(1): 84-91.
7. Ukhanov AP, Zakharov DV. Primary-multiple synchronous cancer of the stomach and colon in elderly patients[J]. Vestn Khir Im II Grek, 2005, 164(2): 80-81.
8. 朱义荣. 多原发癌[J]. 医学理论与实践, 2006, 19(11): 1249-1250.
9. 王成峰, 邵永孚, 张海增, 等. 多原发恶性肿瘤[J]. 中国肿瘤临床, 2000, 27(6): 439-442.
10. Ueno M, Muto T, Oya M, et al. Multiple primary cancer: an experience at the Cancer Institute Hospital with special reference to colorectal cancer[J]. Int J Clin Oncol, 2003, 8(3): 162-167.
11. Beisland C, Talleraas O, Bakke A, et al. Multiple primary malignancies in patients with renal cell carcinoma: a national population-based cohort study[J]. BJU Int, 2006, 97(4): 698-702.
12. Mariotto AB, Rowland JH, Ries LA, et al. Multiple cancer prevalence: a growing challenge in long-term survivorship[J]. Cancer Epidemiol Biomarkers Prev, 2007, 16(3): 566-571.
13. Xu H, Zhang M, Zhai G, et al. The clinical significance of 18F-FDGPET/ CT in early detection of second primary malignancy in cancer patients[J]. J Cancer Res Clin Oncol, 2010, 136(8): 1125-1134.
14. Mercer RR, Lucas NC, Simmons AN, et al. Molecular discrimination of multiple primary versus metastatic squamous cell cancers of the head/neck and lung[J]. Exp Mol Pathol, 2009, 86(1): 1-9.
15. Mhawech-Fauceglia P, Rai H, Nowak N, et al. The use of arraybased comparative genomic hybridization (a-CGH) to distinguish metastatic from primary synchronous carcinomas of the ovary and the uterus[J]. Histopathology, 2008, 53(4): 490-495.
16. 任静, 李学. 多原发癌(六重癌)1例[J]. 中日友好医院学报, 2010, 24(2): 123-124.
17. Moertel CG, Dockerty MB, Baggenstoss AH. Multiple primary malignant neoplasms. Ii. Tumors of different tissues or organs[J]. Cancer, 1961(14): 231-237.
18. Irimie A, Achimas-Cadariu P, Burz C, et al. Multiple primary malignancies--epidemiological analysis at a single tertiary institution[J]. J Gastrointestin Liver Dis, 2010, 19(1): 69-73.
19. Gursel B, Meydan D, Özbek N, et al. Multiple primary malignant neoplasms from the Black Sea region of Turkey[J]. J Int Med Res, 2011, 39(2): 667-674.
20. Giardiello C, Angelone G, Iodice G, et al. Diagnosis, therapy, and follow up in synchronous colorectal cancer of the colon][J]. Il Giornale Di Chirurgia, 2001, 22(4): 122-124.
21. 钟海鸣, 陈景胜, 吴昱冶, 等. 多原发癌86例临床分析[J]. 广东医学院学报, 2009, 27(4): 433-434.
22. Luciani A, Balducci L. Multiple primary malignancies[J]. Semin Oncol, 2004, 31(2): 264-273.
23. Simpkins F, Zahurak M, Armstrong D, et al. Ovarian malignancy in breast cancer patients with an adnexal mass[J]. Obstet Gynecol, 2005, 105(3): 507-513.
24. Cybulski C, Nazarali S, Narod SA. Multiple primary cancers as a guide to heritability[J]. Int J Cancer, 2014, 135(8): 1756-1763.
25. Watson P, Vasen HF, Mecklin JP, et al. The risk of endometrial cancer in hereditary nonpolyposis colorectal cancer[J]. Am J Med, 1994, 96(6): 516-520.
26. Utada M, Ohno Y, Hori M, et al. Incidence of multiple primary cancers and interval between first and second primary cancers[J]. Cancer Sci, 2014, 105(7): 890-896.
27. Talbott VA, Yeo CJ, Brody JR, et al. Molecular profiling of synchronous and metachronous cancers of the pancreas reveal molecular mimicry between samples from the same patient[J]. J Surg Res, 2012, 176(1): 154-158.
28. 任延律, 张岂凡, 于志伟, 等. 大肠重复癌微卫星不稳定性研究[J]. 肿瘤防治研究, 2003, 30(5): 354-356.
29. 王科明, 胡雪珍, 王朝霞, 等. 双原发癌的随访及细胞免疫功能变化[J]. 临床内科杂志, 1998, 15(5): 273-274.
30. Barroso-Vicens E, Ramirez G, Rabb H. Multiple primary malignancies in a renal transplant patient[J]. Transplantation, 1996, 61(11): 1655-1656.
31. Hashibe M, Ritz B, Le AD, et al. Radiotherapy for oral cancer as a risk factor for second primary cancers[J]. Cancer Lett, 2005, 220(2): 185-195.
32. 田雨霖, 佟玉兰, 何三光, 等. 胰癌、食管癌、胃癌三重复癌1例 [J]. 实用外科杂志, 1990, 10(5): 238.
33. Narod SA, Brunet JS, Ghadirian P, et al. Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a case-control study[J]. Lancet, 2000, 356(9245): 1876-1881.
34. Narod SA, Pal T, Graham T, et al. Tamoxifen and risk of endometrial cancer[J]. Lancet, 2001, 357(9249): 65-66.
35. Angurana SL, Kapoor R, Kumar P, et al. Quadruple malignancy in a single patient: a case report and comprehensive review of literature[J]. J Cancer Res Ther, 2010, 6(2): 230-232.
36. Nakashima M, Kondo H, Miura S, et al. Incidence of multiple primary cancers in Nagasaki atomic bomb survivors: association with radiation exposure[J]. Cancer Sci, 2008, 99(1): 87-92.
37. Braisch U, Meyer M, Radespiel-Tröger M. Risk of tobacco-related multiple primary cancers in Bavaria, Germany[J]. BMC Cancer, 2012, 12: 250.
38. Shiels MS, Gibson T, Sampson J, et al. Cigarette smoking prior to first cancer and risk of second smoking-associated cancers among survivors of bladder, kidney, head and neck, and stage I lung cancers[J]. J Clin Oncol, 2014, 32(35): 3989-3995.
39. Gibson TM, Park Y, Robien K, et al. Body mass index and risk of second obesity-associated cancers after colorectal cancer: a pooled analysis of prospective cohort studies[J]. J Clin Oncol, 2014, 32(35): 4004-4011.
40. Bukhtoyarov OV, Samarin DM. Psychogenic carcinogenesis: carcinogenesis is without exogenic carcinogens[J]. Med Hypotheses, 2009, 73(4): 531-536.
41. Gonzalez MJ, Massari JR, Duconge J, et al. The bio-energetic theory of carcinogenesis[J]. Med Hypotheses, 2012, 79(4): 433-439.
42. Anderson MR. Variations in the rate of induction of chemical carcinogenesis according to differing psychological states in rats[J]. Nature, 1964, 204: 55-56.
43. Slaughter DP, Southwick HW, Smejkal W. Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin[J]. Cancer, 1953, 6(5): 963-968.
44. Heroiu CA, Danciu CE, Popescu CR. Multiple cancers of the head and neck[J]. Maedica (Buchar), 2013, 8(1): 80-85.
45. Bedi GC, Westra WH, Gabrielson E, et al. Multiple head and neck tumors: evidence for a common clonal origin[J]. Cancer Res, 1996, 56(11): 2484-2487.
46. Garrean S, Hering J, Saied A, et al. Gastric adenocarcinoma arising from fundic gland polyps in a patient with familial adenomatous polyposis syndrome[J]. Am Surg, 2008, 74(1): 79-83.
47. Hamm A, Veeck J, Bektas N, et al. Frequent expression loss of Interalpha- trypsin inhibitor heavy chain (ITIH) genes in multiple human solid tumors: a systematic expression analysis[J]. BMC Cancer, 2008(8): 25.
48. Shen C, Wang X, Tian L, et al. Microsatellite alteration in multiple primary lung cancer[J]. J Thorac Dis, 2014, 6(10): 1499-1505.
49. 李刚, 吴德昌. 肿瘤相关基因突变是辐射致癌的主要分子事件[J]. 中华放射医学与防护杂志, 1998, 18(3): 214.
50. Sudo H, Garbe J, Stampfer MR, et al. Karyotypic instability and centrosome aberrations in the progeny of finite life-span human mammary epithelial cells exposed to sparsely or densely ionizing radiation[J]. Radiat Res, 2008, 170(1): 23-32.
51. 陈燕青, 周川, 王家东. 头颈部多原发癌[J]. 临床耳鼻咽喉科杂志, 2004, 18(9): 574-576.
52. 徐启明, 孙玉鹗, 刘颖, 等. 肺癌患者的多原发恶性肿瘤[J]. 中国肿瘤临床, 2000, 27(7): 498-501.
53. 王军英, 涂彧, 周菊英. 异时性三原发癌1例[J]. 临床肿瘤学杂志, 2007, 12(9): 720.
54. 王婧, 李琴, 赵志海, 等. 多原发恶性肿瘤的诊疗进展[J]. 医学综述, 2011, 17(10): 1490-1492.
55. Jégu J, Colonna M, Daubisse-Marliac L, et al. The effect of patient characteristics on second primary cancer risk in France[J]. BMC Cancer, 2014, 14: 94.
56. 张世馥, 汪万英, 曹光群, 等. 多原发恶性肿瘤的病理诊断和免疫组织化学研究[J]. 中国肿瘤临床, 1991, 18(5): 347-349, 385.

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