성별에 따른 원발성 폐선암 환자들의 차이

Sex-related Clinicopathologic Differences in Patients with Adenocarcinoma of the Lung

  • 박은호 (고신대학교 의과대학 내과학 교실) ;
  • 장태원 (고신대학교 의과대학 내과학 교실) ;
  • 장리라 (고신대학교 의과대학 내과학 교실) ;
  • 백종현 (고신대학교 의과대학 내과학 교실) ;
  • 옥철호 (고신대학교 의과대학 내과학 교실) ;
  • 정만홍 (고신대학교 의과대학 내과학 교실) ;
  • 장희경 (고신대학교 의과대학 해부병리학 교실)
  • Park, Eun Ho (Department of Internal Medicine, College of Medicine, Kosin University) ;
  • Jang, Tae Won (Department of Internal Medicine, College of Medicine, Kosin University) ;
  • Jang, Li La (Department of Internal Medicine, College of Medicine, Kosin University) ;
  • Paek, Jong yun (Department of Internal Medicine, College of Medicine, Kosin University) ;
  • Oak, Chul Ho (Department of Internal Medicine, College of Medicine, Kosin University) ;
  • Jung, Mann Hong (Department of Internal Medicine, College of Medicine, Kosin University) ;
  • Jang, Hee Kyung (Department of Pathology, College of Medicine, Kosin University)
  • 투고 : 2007.01.15
  • 심사 : 2007.02.23
  • 발행 : 2007.03.30

초록

연구배경: 원발성 폐 선암은 다른 비소세포암에 비해 흡연과의 연관성이 상대적으로 적고 최근 증가 추세에 있으며 여성에서 많이 발생하는 특징을 가진 암종으로 폐 선암의 남녀 차이를 알아보고자 하였다. 대상 및 방법: 1999년 1월부터 2005년 12월까지 고신대학교 병원에 내원하여 폐 선암으로 처음으로 진단된 환자 438명을 대상으로 혈액학적, 흡연력, 돌연변이, 병리조직, 생존 기간 및 치료방법에 따른 반응등을 조사하여 폐 선암으로 진단받은 환자의 남녀간 차이를 비교분석하였다. 결 과: 총 438명의 환자 중 남성이 259명(59.1%), 여성이 179명(40.1%)으로 남성이 많았고, 50세 이전에서의 남녀 유병률은 여성이 25.8%로 남성의 17.7%에 비해 유의하게 높았다(p=0.02). 흡연율은 남성이 86%, 여성이 18%로 남성에서 월등히 높았고(p=0.000), 전체 중간 생존기간은 남성이 639일, 여성이 823일로 여성에서 높았다(p=0.01). 전혈구검사상 혈색소가 12 g/dL 미만인 경우는 여성이 64.6%로 남성의 32.4% 비해 유의하게 높았고(p=0.001), 종양 표지자 중 CEA가 5 ng/ml 이상인 경우는 여성이 68.1%로 남성의 32.1%에 비해 유의하게 높았다(p=0.000). 병기에 따른 남녀 구성비의 차이는 보이지 않았고, EGFR 및 K-ras 돌연변이도 남녀 간 차이는 보이지 않았으며, 조직학적 소견상 기관지 폐포암의 성분을 포함하고 있었던 경우는 여성에서 20명(11.2%), 남성에서 13명(5.0%)으로 여성에서 유의하게 높았다(p=0.035). 수술을 받은 76명의 환자를 다시 항암치료를 받은 군(57명)과 항암치료를 받지 않은 군(19명)으로 나누어 생존기간을 비교한 결과 남녀 모두 항암치료를 병행한 군에서 생존기간이 유의하게 연장되었음을 확인할 수 있었고(p<0.001), 수술만 받은 환자군에서는 남녀간 생존기간의 차이를 보이지 않았지만, 수술과 항암 치료를 병행한 군에서는 통계적 유의성은 가지지 못했으나 남성에 비해 여성에서 생존기간이 더 연장되는 경향을 보였다(p=0.054). 결 론: 폐 선암 환자에서 남녀 성별에 따라 혈액학적, 흡연력, 기관지 폐포암의 구성 비율, 전체 중간 생존 기간 및 치료 방법에 따른 남녀 생존 기간의 차이를 보였다. 따라서 폐 선암의 진단 및 치료에 있어서 이러한 성별에 따른 차이를 반드시 고려해야 할 것이다.

Background: The incidence of adenocarcinoma of the lung has been increasing worldwide, and it has been generally been accepted to be relatively unrelated to smoking with a female preponderance. The aim of this study was to examine the gender-related pathological and survival differences in patients with an adenocarcinoma of the lung. Material and Method: A retrospective review of the clinical information of patients diagnosed with an adenocarcinoma of the lung at Kosin Medical Center from January 1999 to September 2005 was performed. The patient's demographics (age, gender), smoking history, stage, serum tumor marker, pathology classification, EGFR mutation, K-ras mutation, treatment methods, and survival time were analyzed. Result: Of the 438 patients, 179 (40.9%) were female. The median age at the diagnosis was 58 years for females and 59 years for males. However, 25.8% of women and only 17.7% of men were under 50 years of age (p=0.02). The distribution of the disease stage was similar in both men and women. The bronchioloalveolar carcinoma component was diagnosed more often in women (11.2%) than in men (5.0%). The overall survival rate was higher in women than in men (p=0.01), and women had a superior therapeutic response to a combined treatment of surgery and chemotherapy. Conclusion: This study showed significant genders differences in terms of the smoking history, bronchioloalveolar carcinoma component, overall survival, and survival after combined treatment of surgery and chemotherapy. Therefore, gender differences should be considered when diagnosing and treating adenocarcinomas of the lung.

키워드

참고문헌

  1. Fiore MC, Novotny TE, Pierce JP, Hatziandreu EJ, Patel KM, Davis RM. Trends in cigarette smoking in United States: the changing influence of gender and race. JAMA 1989;261:49-55 https://doi.org/10.1001/jama.261.1.49
  2. Henschke CI, Miettinen OS. Women's susceptibility to tobacco carcinogens. Lung Cancer 2004;43:1-5 https://doi.org/10.1016/j.lungcan.2003.08.024
  3. McDuffie HH, Klaassen DJ, Dosman JA. Female-male differences in patients with primary lung cancer. Cancer 1987;59:1825-30 https://doi.org/10.1002/1097-0142(19870515)59:10<1825::AID-CNCR2820591024>3.0.CO;2-2
  4. Brownson RC, Chang JC, Davis JR. Gender and histologic type variations in smoking-related risk of lung cancer. Epidemiology 1992;3:61-4 https://doi.org/10.1097/00001648-199201000-00012
  5. Travis WD, Lubin J, Ries L, Devesa S. United States lung carcinoma incidence trends: declining for most histologic types among males, increasing among females. Cancer 1996;77:2464-70 https://doi.org/10.1002/(SICI)1097-0142(19960615)77:12<2464::AID-CNCR8>3.0.CO;2-M
  6. Radzikowska E, Glaz P, Roszkowski K. Lung cancer in women: age, smoking, histology, performance status, stage, initial treatment and survival. Population based study of 20561 cases. Ann Oncol 2002;13: 1087-93 https://doi.org/10.1093/annonc/mdf187
  7. Osann KE, Anton-Culver H, Kurosaki T, Taylor T. Sex differences in lung-cancer risk associated with cigarette smoking. Int J Cancer 1993;54:44-8 https://doi.org/10.1002/ijc.2910540108
  8. Barsky SH, Cameron R, Osann KE, Tomita D, Holmes EC. Rising incidence of bronchioloalveolar lung carcinoma and its unique clinicopathologic features. Cancer 1994;73:1163-70 https://doi.org/10.1002/1097-0142(19940215)73:4<1163::AID-CNCR2820730407>3.0.CO;2-J
  9. Albertine JH, Steiner RM, Radack DM, Golding DM, Peterson D, Cohn HE, et al. Analysis of cell type and radiographic presentation as predictors of the clinical course of patients with bronchioloalveolar cell carcinoma. Chest 1998;113:997-1006 https://doi.org/10.1378/chest.113.4.997
  10. Thun MJ, Lally CA, Flannery JT, Calle EE, Flanders WD, Heath CW Jr. Cigarette smoking and changes in the histopathology of lung cancer. J Natl Cancer Inst 1997;89:1580-6 https://doi.org/10.1093/jnci/89.21.1580
  11. Muscat JE, Wynder EL. Lung cancer pathology in smokers, ex-smokers and never smokers. Cancer Lett 1995;88:1-5 https://doi.org/10.1016/0304-3835(94)03608-L
  12. Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Douillard JY, et al. Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial). J Clin Oncol 2003;21:2237-46 https://doi.org/10.1200/JCO.2003.10.038
  13. de Perrot M, Licker M, Bouchardy C, Usel M, Robert J, Spiliopoulos A. Sex differences in presentation, management, and prognosis of patients with non-small cell lung carcinoma. J Thorac Cardiovasc Surg 2000;119:21-6 https://doi.org/10.1016/S0022-5223(00)70213-3
  14. Etzel CJ, Lu M, Merriman K, Liu M, Vaporciyan A, Spitz MR. An epidemiologic study of early onset lung cancer. Lung cancer 2006;52:129-34 https://doi.org/10.1016/j.lungcan.2005.11.018
  15. Fu JB, Kau TY, Severson RK, Kalemkerian GP. Lung cancer in women: analysis of the national Surveillance, Epidemiology, and End Results database. Chest 2005;127:768-77 https://doi.org/10.1378/chest.127.3.768
  16. O'Connell JP, Kris MG, Gralla RJ, Groshen S, Trust A, Fiore JJ, et al. Frequency and prognostic importance of pretreatment clinical characteristics in patients with advanced non-small-cell lung cancer treated with combination chemotherapy. J Clin Oncol 1986;4:1604-14 https://doi.org/10.1200/JCO.1986.4.11.1604
  17. Minami H, Yoshimura M, Miyamoto Y, Matsuoka H, Tsubota N. Lung cancer in women: sex-associated differences in survival of patients undergoing resection for lung cancer. Chest 2000;118:1603-9 https://doi.org/10.1378/chest.118.6.1603
  18. Alexiou C, Onyeaka CV, Beggs D, Akar R, Beggs L, Salama FD, et al. Do women live longer following lung resection for carcinoma? Eur J Cardiothorac Surg 2002;21:319-25 https://doi.org/10.1016/S1010-7940(01)01114-9
  19. Ferguson MK, Wang J, Hoffman PC, Haraf DJ, Olak J, Masters GA, et al. Sex-associated differences in survival of patients undergoing resection for lung cancer. Ann Thorac Surg 2000;69:245-50 https://doi.org/10.1016/S0003-4975(99)01078-4
  20. Risch HA, Howe GR, Jain M, Burch JD, Holowaty EJ, Miller AB. Are female smokers at higher risk for lung cancer than male smokers? A case control analysis by histologic type. Am J Epidemiol 1993;138:281-93 https://doi.org/10.1093/oxfordjournals.aje.a116857
  21. Kure EH, Ryberg D, Hewer A, Phillips DH, Skaug V, Baera R, et al. p53 mutations in lung tumours: relationship to gender and lung DNA adduct levels. Carcinogenesis 1996;17:2201-5 https://doi.org/10.1093/carcin/17.10.2201
  22. Ryberg D, Hewer A, Phillips DH, Haugen A. Different susceptibility to smoking-induced DNA damage among male and female lung cancer patients. Cancer Res 1994;54:5801-3
  23. Mollerup S, Ryberg D, Hewer A, Phillips DH, Haugen A. Sex differences in lung CYP1A1 expression and DNA adduct levels among lung cancer patients. Cancer Res 1999;59:3317-20
  24. Nelson HH, Christiani DC, Mark EJ, Wiencke JK, Wain JC, Kelsey KT. Implications and prognostic value of K-ras mutation for early-stage lung cancer in women. J Natl Cancer Inst 1999;91:2032-8 https://doi.org/10.1093/jnci/91.23.2032
  25. Caracta CF, Powell C, Brody JS. Estrogen receptor status of lung cancer cell lines [abstract]. Am J Respir Crit Care Med 1999;159:A204
  26. Denissenko MF, Pao A, Tang M, Pfeifer GP. Preferential formation of benzo$ [{\alpha}]$ pyrene adducts at lung cancer mutational hotspots in p53. Science 1996;274:430-2 https://doi.org/10.1126/science.274.5286.430
  27. Tredaniel J, Boffetta P, Saracci R, Hirsch A. Exposure to environmental tobacco smoke and risk of lung cancer: the epidemiological evidence. Eur Respir J 1994;7:1877-88 https://doi.org/10.1183/09031936.94.07101877
  28. Schwartz AG, Yang P, Swanson GM. Familial risk of lung cancer among nonsmokers and their relatives. Am J Epidemiol 1996;144:554-62 https://doi.org/10.1093/oxfordjournals.aje.a008965
  29. Ooi WL, Elston RC, Chen VW, Bailey-Wilson JE, Rothschild H. Increased familial risk for lung cancer. J Natl Cancer Inst 1986;76:217-22
  30. Ko YC, Cheng LS, Lee CH, Huang JJ, Huang MS, Kao EL, et al. Chinese food cooking and lung cancer in women nonsmokers. Am J Epidemiol 2000;151: 140-7 https://doi.org/10.1093/oxfordjournals.aje.a010181
  31. Beckett WS. Epidemiology and etiology of lung cancer. Clin Chest Med 1993;14:1-15
  32. Cheng YW, Chiou HL, Sheu GT, Hsieh LL, Chen JT, Chen CY, et al. The association of human papillomavirus 16/18 infection with lung cancer among nonsmoking Taiwanese women. Cancer Res 2001;61: 2799-803
  33. Mayne ST, Buenconsejo J, Janerich DT. Previous lung disease and risk of lung cancer among men and women nonsmokers. Am J Epidemiol 1999;149:13-20 https://doi.org/10.1093/oxfordjournals.aje.a009722
  34. Fasco MJ, Hurteau GJ, Spivack SD. Genderdependent expression of alpha and beta estrogen receptors in human nontumor and tumor lung tissue. Mol Cell Endocrinol 2002;188:125-40 https://doi.org/10.1016/S0303-7207(01)00750-X
  35. Omoto Y, Kobayashi Y, Nishida K, Tsuchiya E, Eguchi H, Nakagawa K, et al. Expression, function, and clinical implications of estrogen receptor ${\beta}$ in human lung cancers. Biochem Biophys Res Commun 2001;285:340-7 https://doi.org/10.1006/bbrc.2001.5158
  36. Taioli E, Wynder EL. Re: Endocrine factors and adenocarcinoma of the lung in women. J Natl Cancer Inst 1994;86:869-70 https://doi.org/10.1093/jnci/86.11.869
  37. Barkley JE, Green MR. Bronchioloalveolar carcinoma. J Clin Oncol 1996;14:2377-86 https://doi.org/10.1200/JCO.1996.14.8.2377
  38. Yoshino I, Baba H, Fukuyama S, Kameyama T, Shikada Y, Tomiyasu M, et al. A time trend of profile and surgical results in 1123 patients with non-small cell lung cancer. Surgery 2002;131:S242-8 https://doi.org/10.1067/msy.2002.119796
  39. Hirsch F, Veve R, Varella-Garcia M. Evaluation of HER-2/neu expression on lung tumors by immunohistochemistry and fluorescence in situ hybridization [abstract]. Proc Am Soc Clin Oncol 2000;19:486A
  40. Rachwal WJ, Bongiorno PF, Orringer MB, Whyte RI, Ethier SP, Beer DG. Expression and activation of erb-2 and epidermal growth factor receptor in lung adenocarcinomas. Br J Cancer 1995;72:56-64 https://doi.org/10.1038/bjc.1995.277
  41. Wei Q, Cheng L, Amos CI, Wang LE, Guo Z, Hong WK, et al. Repair of tobacco carcinogen-induced DNA adducts and lung cancer risk: a molecular epidemiological study. J Natl Cancer Inst 2000;92:1764-72 https://doi.org/10.1093/jnci/92.21.1764
  42. Spitz MR, Wei Q, Dong Q, Amos CI, Wu X. Genetic susceptibility to lung cancer: the role of DNA damage and repair. Cancer Epidemiol Biomarkers Prev 2003;12:689-98
  43. Lord RV, Brabender J, Gandara D. Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer. Clin Cancer Res 2002;8:2286-91
  44. Werner-Wasik M, Scott C, Cox JD, Sause WT, Byhardt RW, Asbell S, et al. Recursive partitioning analysis of 1999 Radiation Therapy Oncology Group (RTOG) patients with locally-advanced non-small cell lung cancer (LA-NSCLC): identification of five groups with different survival. Int J Radiat Oncol Biol Phys 2000;48:1475-82 https://doi.org/10.1016/S0360-3016(00)00801-4
  45. Albain KS, Crowley JJ, LeBlanc M, Livingston RB. Survival determinants in extensive-stage non-small cell lung cancer: the Southwest Oncology Group experience. J Clin Oncol 1991;9:1618-26 https://doi.org/10.1200/JCO.1991.9.9.1618