Pneumologie 2013; 67(05): 270-279
DOI: 10.1055/s-0033-1343149
Serie: Genderfragen in der Pneumologie
© Georg Thieme Verlag KG Stuttgart · New York

Geschlechtsspezifische Unterschiede beim Lungenkarzinom

Gender-Specific Difference in Lung Cancer
M. Serke
Pneumologie, Lungenklinik Hemer
,
F. Stanzel
Pneumologie, Lungenklinik Hemer
,
M. Westhoff
Pneumologie, Lungenklinik Hemer
› Author Affiliations

Subject Editor: C. Grohé, Berlin
Further Information

Publication History

eingereicht 12 February 2013

akzeptiert nach Revision 22 March 2013

Publication Date:
15 May 2013 (online)

Zusammenfassung

Epidemiologisch zeigt sich in Deutschland, in Europa und in den USA eine zunehmende Lungenkrebshäufigkeit bei Frauen! Besonders der Vergleich der altersspezifischen Erkrankungsraten nach Geschlecht zeigt bei jüngeren Frauen eine höhere Lungenkrebserkrankungsrate als bei Männern. Histologisch sind bei Frauen mehr Adenokarzinome als bei Männern zu beobachten. Ursächlich sind einerseits sicherlich die geänderten Rauchgewohnheiten der Frauen, zusätzlich spielen aber noch andere Faktoren bei der Lungenkrebs-Karzinogenese der Frauen eine Rolle. Wesentlich häufiger manifestiert sich der Nichtraucher-Lungenkrebs bei Frauen als bei Männern. Ursächlich könnten unterschiedliche Lungenkrebs-Empfänglichkeiten oder auch unterschiedliche Karzinogen-Expositionen, z. B. gegenüber Radon, durch Passivrauchen oder Herddämpfe der Geschlechter sein. Auf molekularer Ebene finden sich bei Frauen häufiger genetische „Treiber-Mutationen“ als bei Männern und demzufolge können neue „zielgerichtete Therapien“, z. B. gegen EGFR oder Alk, häufiger bei Frauen zum Einsatz kommen. Die Prognose beim klein- und nichtkleinzelligen Lungenkarzinom ist bei Frauen insgesamt etwas besser als bei Männern.

Abstract

More and more differences in lung cancer are being detected between men and women. Lung cancer, at the beginning of the last century a rare disease in women, has a growing incidence in women, in particular in young females. Lung cancer is a leading cause of cancer death in women in developed countries with different histological types and adenocarcinomas are more frequent in women than in men. Cigarette smoking is the most prevalent cause of lung cancer in women, in addition susceptibility to carcinogens may differ between the sexes. As more non-smoking women than men develop lung cancer, it is likely that they are exposed to excessive environmental carcinogens such as second-hand-smoking, in-house-radon or cooking fumes. Furthermore, genetic and hormonal influences play a role in lung cancer etiology for women. Taken together, women have a better overall survival than men with lung cancer. Differences in molecular susceptibility patterns are observed between men and women, and show that molecular targets such as EGFR or ALK more frequent in women.

 
  • Literatur

  • 1 Malvezzi M, Arfe A, Bertuccio P. European cancer mortality predictions for the year 2011. Ann Oncol 2011; 22: 947-956
  • 2 Jemal A, Siegel R, Ward E et al. Cancer statistics 2004. CA Cancer J Clin 2006; 56: 106-130
  • 3 Patel JD. Lung Cancer in Women. J Clin Oncol 2005; 23: 3212-3218
  • 4 American Cancer Society. Cancer facts and figures. Atlanta, GA: American Cancer Society; 2010
  • 5 Thun MJ, Carter BD, Feskanich D. 50-Year Trends in Smoking-Related Mortality in the United States. N Engl J Med 2013; 368: 4
  • 6 Haiman CA, Stram DO, Wilkens LR et al. Ethnic and racial differences in the smoking-related risk of lung cancer. N Engl J Med 2006; 354: 333-342
  • 7 Robert Koch-Institut und die Gesellschaft der epidemiologischen Krebsregister in Deutschland e.V. Hrsg. Krebs in Deutschland 2007/2008. 8.. Ausgabe. Berlin: 2012
  • 8 Jemal A, Thun MJ, Ries LA et al. Annual report to the nation on the status of cancer, 1975-2005, featuring trends in lung cancer, tobacco use, and tobacco control. J Natl Cancer Inst 2008; 100: 1672-1694
  • 9 World Health Organization. Women and health: today’s evidence, tomorrow’s agenda. Geneva, Switzerland: World Health Organization Press; 2009
  • 10 Klingerman S, White C. Epidemiology of Lung Cancer in Women: Risk Factors, Survival, and Screening. AJR 2011; 196: 287-295
  • 11 Pirie K, Peto R, Reeves GK et al. The 21st century hazards of smoking and benefits of stopping: a prospective study of one million women in the UK. Lancet 2013; 381: 133-141
  • 12 Laue E. Statistisches Bundesamt Wiesbaden; 2010
  • 13 Risch HA, Howe GR, Jain M et al. Are female smokers at higher risk for lung cancer than male smokers? A case-control analysis by histologic type. Am J Epidemiol 1993; 138: 281-293
  • 14 Feskanich D, Ziegler RG, Michaud DS et al. Prospective study of fruit and vegetable consumption and risk of lung cancer among men and women. J Natl Cancer Inst 2000; 92: 1812-1823
  • 15 Henschke CI, Yip R, Miettinen OS. International Early Lung Cancer Action Program Investigators. Women’s susceptibility to tobacco carcinogens and survival after diagnosis of lung cancer. JAMA 2006; 296: 180-184
  • 16 Ryu JS, Jeon SH, Kim JS. Gender Differences in Susceptibility to Smoking among Patients with Lung Cancer. Korean J Intern Med 2011; 26: 427-431
  • 17 Freedman ND, Leitzmann MF, Hollenbeck AR et al. Cigarette smoking and subsequent risk of lung cancer in men and women: analysis of a prospective cohort study. Lancet Oncol 2008; 9: 649-656
  • 18 Bain C, Feskanich D, Speizer F et al. Lung cancer rates in men and women with comparable histories of smoking. J Natl Cancer Inst 2004; 96: 826-834
  • 19 Subramanian J, Govindan R. Lung cancer in never smokers: A review. J Clin Oncol 2007; 25: 561-570
  • 20 Gorlova OY, Weng SF, Zhang Y et al. DNA repair capacity and lung cancer risk in never smokers. Cancer Epidemiol Biomarkers Prev 2008; 17: 1322-1328
  • 21 Wei Q, Cheng L, Amos CI et al. Repair of tobacco carcinogen-induced DNA adducts and lung cancer risk: a molecular epidemiologic study. J Natl Cancer Inst 2000; 92: 1764-1772
  • 22 Planchard D, Loriot Y, Goubar A et al. Differential expression of biomarkers in men and women. Semin Oncol 2009; 36: 553-565
  • 23 Mollerup S, Ryberg D, Hewer A et al. Sex differences in lung CYP1A1 expression and DNA adduct levels among lung cancer patients. Cancer Res 1999; 59: 3317-3320
  • 24 Bell D, Taylor J, Paulson D et al. Genetic risk and carcinogen exposure:a common inherited defect of the carcinogen-metabolism gene glutathione S-transferase M1 (GSTM1) that increases susceptibility to bladder cancer. J Natl Cancer Inst 1993; 85: 1159-1164
  • 25 Dresler C, Fratelli C, Babb J et al. Gender differences in genetic susceptibility for lung cancer. Lung Cancer 2000; 30: 153-160
  • 26 Hackshaw AK, Law MR, Wald NJ. The accumulated evidence on lung cancer and environmental tobacco smoke. BMJ 1997; 315: 980-988
  • 27 Öberg M, Jaakkola MS, Woodward A. Worldwide burden of disease from exposure to second-hand smoke: a retrospective analysis of data from 192 countries. The Lancet 2011; 377, 760: 139-146
  • 28 Tredaniel J, Boffetta P, Saracci R et al. Non-smoker lung cancer deaths attributable to exposure to spouse’s environmental tobacco smoke. Int J Epidemiol 1997; 26: 939-944
  • 29 Vineis P, Alavanja M, Buffler P et al. Tobacco and cancer: Recent epidemiological evidence. J Natl Cancer Inst 2004; 96: 99-106
  • 30 World Health Organization. WHO Report on the Global Tobacco Epidemic. Geneva, Switzerland: World Health Organization Press; 2008
  • 31 Sun S, Schiller JH, Gazdar AF. Lung cancer in never smokers – a different disease. Nat Rev Cancer 2007; 7 (10) 778-790
  • 32 Toh CK. Never smokers with lung cancer. J Clin Oncol 2006; 24: 2245-2251
  • 33 Wakelee HA, Chang ET, Gomez SL et al. Lung cancer incidence in never smokers. J Clin Oncol 2007; 25: 472-478
  • 34 Kawaguchi T, Takada M, Kubo A. Gender, Histology, and Time of Diagnosis Are Important Factors for Prognosis. Analysis of 1499 Never-Smokers with Advanced Non-small Cell Lung Cancer in Japan. J Thorac Oncol 2010; 5: 1011-1017
  • 35 Nordquist LT, Simon GR, Cantor A et al. Improved survival in never-smokers vs current smokers with primary adenocarcinoma of the lung. Chest 2004; 126: 347-351
  • 36 Field RW, Steck DJ, Smith BJ et al. Residential radon gas exposure and lung cancer: the Iowa Radon Lung Cancer Study. Am J Epidemiol 2000; 151: 1091-1102
  • 37 Ko YC, Cheng LS, Lee CH et al. Chinese food cooking and lung cancer in women nonsmokers. Am J Epidemiol 2000; 151: 140-147
  • 38 Matakidou A, Eisen T, Houlston RS. Systematic review of the relationship between family history and lung cancer risk. Br J Cancer 2005; 93: 825-833
  • 39 Wu A, Fontham E, Reynolds P et al. Family history of cancer and risk of lung cancer among lifetime nonsmoking women in the United States. Am J Epidemiol 1996; 143: 535-542
  • 40 Wu PF, Lee CH, Wang MJ et al. Cancer aggregation and complex segregation analysis of families with female non-smoking lung cancer probands in Taiwan. Eur J Cancer 2004; 40: 260-266
  • 41 Mok TS, Wu YL, Thongprasert S et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947-957
  • 42 Mitsudomi T, Morita S, Yatabe Y et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJ-TOG3405): an open label, randomised phase 3 trial. Lancet Oncol 2010; 11: 121-128
  • 43 Maemondo M, Inoue A, Kobayashi K et al. Gefitinib or chemotherapy for nonsmall-cell cancer with mutated EGFR. N Engl J Med 2010; 362: 2380-2388
  • 44 Rosell R, Carcereny E, Gervais R et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 2012; 13: 239-246
  • 45 Zhou C, Wu YL, Chen G et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicenter, open-label, randomized, phase 3 study. Lancet Oncol 2011; 12: 735-742
  • 46 Kris MG, Natale RB, Herbst RS. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small-cell lung cancer: a randomized trial. JAMA 2003; 290: 2149-2158
  • 47 Herbst RS, Giaccone G, Schiller J. Subset analysis of INTACT results for gefitinib (ZD1839) when combined with platinum based chemotherapy for advanced non-small-cell lung cancer (Abstract). Proc Am Soc Clin Oncol 2003; 22: 627
  • 48 Thatcher N, Chang A, Parikh P et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: Results from a randomised, placebocontrolled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet 2005; 366: 1527-1537
  • 49 Shepherd FA, Rodrigues Pereira J, Ciuleanu T et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005; 353: 123-132
  • 50 Toyooka S, Tsuda T, Gazdar AF. The TP53 gene, tobacco exposure, and lung cancer. Hum Mutat 2003; 21: 229-239
  • 51 Sun Y, Ren Y, Fang Z et al. Lung Adenocarcinoma From East Asian Never-Smokers Is a Disease Largely Defined by Targetable Oncogenic Mutaal.nt Kinases. J Clin Oncol 2010; 28: 4616-4620
  • 52 Lee YJ, Cho BC, Jee SH et al. Impact of Environmental Tobacco Smoke on the Incidence of Mutations in Epidermal Growth Factor Receptor Gene in Never-Smoker Patients With Non–Small-Cell Lung Cancer. J Clin Oncol 2009; 28: 487-492
  • 53 Shao YY, Shau WY, Lin ZZ. Comparison of gefitinib and erlotinib efficacies as third-line therapy for advanced non-small-cell lung cancer. Eur J Cancer 2013; 49 (Suppl. 01) 106-114
  • 54 Yang JCH, Schuler MH, Yamamoto N. LUX-Lung 3: A randomized, open-label, phase III study of afatinib versus pemetrexed and cisplatin as first-line treatment for patients with advanced adenocarcinoma of the lung harboring EGFR-activating mutations. J Clin Oncol 2012; 30 abstr LBA7500
  • 55 Sandler A, Gray R, Perry MC et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 2006; 355: 2542-2550
  • 56 Brahmer JR, Dahlberg SE, Gray RJ et al. Sex differences in outcome with bevacizumab therapy: analysis of patients with advanced-stage non-small cell lung cancer treated with or without bevacizumab in combination with paclitaxel and carboplatin in the Eastern Cooperative Oncology Group Trial 4599. J Thorac Oncol 2011; 6: 103-108
  • 57 Pirker R, Pereira JR, Szczesna A et al. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet 2009; 373: 1525-1531
  • 58 Kure EH, Ryberg D, Hewer A et al. p53 mutations in lung tumours: relationship to gender and lung DNA adduct levels. Carcinogenesis 1996; 17 (10) 2201-2205
  • 59 Petersen I. Morphologische und molekulare Diagnostik des Lungenkarzinoms. Dtsch Arztebl Int 2011; 108: 525-531 DOI: 10.3238/arztebl.2011.0525.
  • 60 Nelson HH, Christiani DC, Mark EJ et al. Implications and prognostic value of K-ras mutation for early-stage lung cancer in women. J Natl Cancer Inst 1999; 91: 2032-38
  • 61 Shaw AT, Yeap BY, Mino-Kenudson M. Clinical Features and Outcome of Patients With Non–Small-Cell Lung Cancer Who Harbor EML4-ALK. JCO 2009; 27, 26: 4247-4253
  • 62 Meert AP, Martin B, Paesmans M et al. The role of HER-2/neu expression on the survival of patients with lung cancer: a systematic review of the literature. Br J Cancer 2003; 89: 959-965
  • 63 Nakamura H, Kawasaki N, Taguchi M et al. Association of HER-2 overexpression with prognosis in nonsmall cell lung carcinoma: a metaanalysis. Cancer 2003; 103: 1865-1873
  • 64 Al-Saad S, Al-Shibli K, Donnem T. Clinical Significance of Epidermal Growth Factor Receptors in Non-small Cell Lung Cancer and a Prognostic Role for HER2 Gene Copy Number in Female Patients. J Thorac Oncol 2010; 5: 1536-1543
  • 65 Rosell R. Toward customized trastuzumab in HER-2/neu-overexpressing non-small-cell lung cancers. J Clin Oncol 2004; 22: 1171-1173
  • 66 Cappuzzo F, Bemis L, Varella-Garcia M. HER2 mutation and response to trastuzumab therapy in non-small-cell lung cancer. N Engl J Med 2006; 354: 2619-2621
  • 67 Gatzemeier U, Groth G, Butts C et al. Randomized phase II trial of gemcitabine-cisplatin with or without trastuzumab in HER2-positive non-small-cell lung cancer. Ann Oncol 2004; 15: 19-27
  • 68 Marchetti A, Felicioni L, Malatesta S. Clinical Features and Outcome of Patients With Non-Small-Cell Lung Cancer Harboring BRAF Mutations. J Clin Oncol 2011; 29: 3574-3579
  • 69 Dannenberg K, Brabender J, Schneider S et al. Gender differences in the predictive power of prognostic factors in NSCLC (Abstract). Proc Am Soc Clin Oncol 2004; 22 (Abstract 619s)
  • 70 Schabath MB, Wu X, Vassilopoulou-Sellin R et al. Hormone replacement therapy and lung cancer risk: a case control analysis. Clin Cancer Res 2004; 10: 113-123
  • 71 Chlebowski RT, Schwartz AG, Wakelee H et al. Women’s Health Initiative Investigators. Oestrogen plus progestin and lung cancer in postmenopausal women (Women’s Health Initiative trial): a post-hoc analysis of a randomised controlled trial. Lancet 2009; 374: 1243-1251
  • 72 Gasperino J. Gender is a risk factor for lung cancer. Med Hypotheses 2011; 76: 328-31
  • 73 Traynor AM, Schiller JH, Stabile LP et al. Combination therapy with gefitinib and fulvestrant (G/F) for women with non-small-cell lung cancer (NSCLC) (Abstract). Proc Am Soc Clin Oncol 2005; 23: 16S
  • 74 Wakelee HA, Dahlberg SE, Schiller JH et al. Menopausal status of women may affect survival in advanced NSCLC: Analysis of recent Eastern Cooperative Oncology Group (ECOG) studies using age of 60 years or older as a surrogate marker. 12th World Conference on Lung Cancer Proceedings 2007; 2 (Suppl. 04) 570 (Abstr #P1052)
  • 75 Patel JD, Bach PB, Kris MG. Lung cancer in US women: a contemporary epidemic. JAMA 2004; 291: 1763-1768
  • 76 Nakamura H, Shinmyo AK, Mochizuki A. Female gender is an independent prognostic factor in non-small-cell lung cancer: a meta-analysis. Annals Thor Cardiovasc Surg 2011; 17: 469-480
  • 77 Keller SM, Vangel MG, Adak S. The influence of gender on survival and tumor recurrence following adjuvant therapy of completely resected stages II and IIIa non-small cell lung cancer. Lung Cancer 2002; 37: 303-309
  • 78 Edmonson JH, Lagakos SW, Selawry OS. Cyclosphosphamide and CCNU in the treatment of inoperable small cell carcinoma and adenocarcinoma of the lung. Cancer Treat Rep 1976; 60: 925-932
  • 79 Moore R, Doherty D, Chamberlain R et al. Sex differences in survival in non-small-cell lung cancer patients 1974–1998. Acta Oncol 2004; 43: 57-64
  • 80 Wisnivesky JP, Halm EA. Sex differences in lung cancer survival: do tumors behave differently in elderly women?. J Clin Oncol 2007; 25: 1705-1712
  • 81 Asamura H, Goya T, Koshiishi Y. A Japanese Lung Cancer Registry study: prognosis of 13,010 resected lung cancers. J Thorac Oncol 2008; 3: 46-52
  • 82 Minami H, Yoshimura M, Miyamoto Y et al. Lung cancer in women: sex-associated differences in survival of patients undergoing resection for lung cancer. Chest 2000; 118: 1603-1609
  • 83 Visbal AL, Williams BA, Nichols III FC et al. Gender differences in non-small-cell lung cancer survival: an analysis of 4,618 patients diagnosed between 1997 and 2002. Ann Thorac Surg 2004; 78: 209-215
  • 84 Cerfolio RJ, Bryant AS, Scott E et al. Women with pathologic stage I, II, and III non-small cell lung cancer have better survival than men. Chest 2006; 130 (06) 1796-1802
  • 85 LaPar DJ, Bhamidipati CM, Harris DA. Gender, Race and Socioeconomic Status Affects Outcomes Following Lung Cancer Resections in the United States. Ann Thorac Surg 2011; 92: 434-439
  • 86 Werner-Wasik M, Scott C, Cox JD 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: 1475-1482
  • 87 Albain KS, Unger J, Gotay CC et al. Toxicity and survival by sex in patients with advanced non-small cell lung carcinoma (NSCLC) on modern Southwest Oncology Group (SWOG) trials. 2007 ASCO Annual Meeting Proceedings (Post-Meeting Edition). J Clin Oncol 2007; 25: 7549
  • 88 Siddiqui F, Bae K, Langer CJ. The Influence of Gender, Race, and Marital Status on Survival in Lung Cancer Patients. Analysis of Radiation Therapy Oncology Group Trials. J Thorac Oncol 2010; 5: 631-639
  • 89 McGovern SL, Liao Z, Bucci K et al. Is Sex Associated With the Outcome of Patients Treated With Radiation for Nonsmall Cell Lung Cancer?. Cancer 2009; 115 (Suppl. 14) 3233-3242
  • 90 Paesmans M, Sculier JP, Libert G. Prognostic factors for survival in advanced non-small-cell lung cancer: univariate and multivariate analyses including recursive partitioning and amalgamation algorithms in 1,052 patients. J Clin Oncol 1995; 13: 1221-1230
  • 91 Schiller JH, Harrington D, Belani CP et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002; 346: 92-98
  • 92 Wakelee HA, Wang W, Schiller JH et al. Survival differences by sex for patients with advanced non-small cell lung cancer on Eastern Cooperative Oncology Group trial 1594. J Thorac Oncol 2006; 1: 441-446
  • 93 Wakelee HA, Dahlberg SE, Schiller JH et al. Menopausal status of women may affect survival in advanced NSCLC: analysis of recent Eastern Cooperative Oncology Group (ECOG) studies using age of 60 years or older as a surrogate marker. J Thorac Oncol 2007; 2: 570 Abstract P1052
  • 94 Albain KS, Unger J, Gotay CC et al. Toxicity and survival by sex in patients with advanced non-small cell lung carcinoma (NSCLC) on modern Southwest Oncology Group (SWOG) trials. Proc Am Soc of Clin Oncol 2007; 25: 396s Abstract 7549
  • 95 Paesmans M, Sculier JP, Lecomte J et al. Prognostic factors for patients with small cell lung carcinoma: analysis of a series of 763 patients included in 4 consecutive prospective trials with a minimum follow-up of 5 years. Cancer 2000; 89: 523-33
  • 96 Johnson BE, Steinberg SM, Phelps R et al. Female patients with small cell lung cancer live longer than male patients. Am J Med 1988; 85: 194-196
  • 97 Albain KS, Crowley JJ, LeBlanc M et al. Determinants of improved outcome in small-cell lung cancer: an analysis of the 2,580-patient Southwest Oncology Group database. Am J Clin Oncol 1990; 8: 1563-1574
  • 98 Singh W, Parulekar N, Murray R et al. Influence of gender on treatment outcome and toxicity in small cell lung cancer (SCLC) (Abstract). Proc Am Soc Clin Oncol 2004; 22: 14S