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Women Have Potential Increase in Risk from Smoking

Research findings on the increased risk of lung cancer in women smokers, DNA repair capacity implications, survival differences based on gender in lung cancer treatment studies, and the impact of menopausal status and K-ras mutations on lung cancer outcomes.

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Women Have Potential Increase in Risk from Smoking

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  1. Women Have Potential Increase in Risk from Smoking 1. Risch HA, et al. Am J Epidemiol. 1993;138:281. 2. Harris RE, et al. Int J Epidemiol. 1993;22:592. 3. Zang EA, et al. J Natl Cancer Inst. 1996;88:183. 4. Osann KE, et al. Int J Cancer. 1993;22:44. 5. Henschke CI, et al. Lung Cancer. 2004;43:1.

  2. Other Studies Show No Increased Risk for Women Smokers 1. Kreuzer M, et al. Br J Cancer. 2000;82:227-233. 2. Halpern MT, et al. J Natl Cancer Inst. 1993;85:422-423. 3. Bach PB, et al. J Natl Cancer Inst. 2003;95:470-478.

  3. DNA Repair Capacity (DRC) • Bulky DNA lesions from tobacco repaired by nucleotide excision repair pathway •  DRC leads to risk of lung cancer1,2 •  DRC in people <60 years old, women, those with positive family history • However,  DRC may improve response to chemotherapy3 1. Wei Q, et al. J Natl Cancer Inst. 2000; 92:1764. 2. Spitz MR, et al. Cancer Epidemiol Biomarkers Prev. 2003;12:689. 3. Lord RVN, et al. Clin Cancer Res. 2002;8:2286.

  4.  CYP1A1 expression significantly correlates with  levels of DNA adducts per pack-year smoking history CYP1A1 40 32 24 DNA-Adducts/108 Nucleotides 16 8 r = 0.50P = .009 0 0 300 600 900 1200 CYP1A1/106 GAPDH Mollerup S, et al. Cancer Res. 1999;59:3317.

  5. Survival Differences by Gender in E1594* Improvement in survival remained even when adjusted for performance status, weight loss, brain metastases, and stage. *Patients treated with 1 of 4 platinum doublets. Wakelee HA, et al. J Thorac Oncol. 2006;1:441.

  6. E1594 Toxicity* No difference in leukopenia, thrombocytopenia, anemia, coagulation, infection, diarrhea, stomatitis, hepatitic toxicity, hypertension/hypotension. *Patients treated with 1 of 4 platinum doublets. Wakelee HA, et al. J Thorac Oncol. 2006;1:441.

  7. Survival Differences by Gender in E4599* OS = overall survival; HR = hazard ratio; PFS = progression-free survival; RR = response rate. *Patients treated with carboplatin/paclitaxel/bevacizumab vs carboplatin/paclitaxel. Brahmer J, et al. J Clin Oncol. 2007;24(18S). Abstract 7036.

  8. Gender Differences in E4599 • Higher proportion of women on carboplatin/paclitaxel/bevacizumab compared with paclitaxel/carboplatin with liver involvement (P = .003) and slightly higher proportion with prior weight loss • Higher proportion of women on the carboplatin/paclitaxel/bevacizumab compared with men on the carboplatin/paclitaxel/bevacizumab arm had hypertension (P = .02) • More grade 5 febrile neutropenia experienced by women than by men on carboplatin/paclitaxel/bevacizumab (P = .03) • No differences in % receiving maintenance bevacizumab or 2nd-line treatment Brahmer J, et al. J Clin Oncol. 2007;24(18S). Abstract 7036.

  9. Menopausal Status of Women Affects Survival with Advanced NSCLCCombined Analysis of E1594 and E4599 Confirmed similar results by SWOG, presented at ASCO 20072 1. Wakelee HA, et al. J Thorac Oncol. 2007;2(8 suppl 4).Abstract P1-052. 2. Albain K, et al. J Clin Oncol. 2007;25(18S). Abstract 7549.

  10. K-ras Mutations • Promotes cancer growth in response to estrogen and other hormones • Significant association between female gender and K-ras mutation after adjustment for carcinogen exposure (OR = 3.3) • K-ras mutations  in resected lung cancers from female vs male smokers Nelson HH, et al. J Natl Cancer Inst. 1999;91:2032.

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