Never-Smokers With Lung Cancer: Epidemiologic Evidence of a Distinct Disease Entity

Toh, Chee-Keong; Gao, Fei; Lim, Darren Wan-Teck; Leong, Siew Meng; Fong, Kok‐Yong; Yap, Swee-Peng; Hsu, Anne Ann Ling; Eng, Philip; Koong, Heng Nung; Agasthian, Thirugnanam; Tan, Eng‐Huat

doi:10.1200/jco.2005.04.8033

Cited by 328 publications

(274 citation statements)

References 29 publications

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“…Furthermore, the current guidance of routine EGFR mutation analysis in NSCLC patients was validated. Our conclusion seems to be discordant with the results of the majority of earlier studies (5,9,12,15). The univariate analysis with Pearson's χ 2 test or Fisher's exact test, or the ULR model used in the present and the majority of previous studies (5,9,12,15), led to the conclusion that NSCLC patients characterized by female gender, never-smoking status and adenocarcinoma histology were more likely to harbor EGFR mutations (Table I).…”

Section: Discussioncontrasting

confidence: 53%

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Histological subtype and smoking status, but not gender, are associated with epidermal growth factor receptor mutations in non-small-cell lung cancer

Hsiao¹,

Lin

Chou

et al. 2013

Molecular and Clinical Oncology

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Abstract. Mutations in epidermal growth factor receptor (EGFR) commonly occur in non-small-cell lung cancer (NSCLC) patients characterized by female gender, never-smoker status and adenocarcinoma histology. The aim of this study was to determine whether gender is a confounding factor for EGFR mutations in NSCLC. To elucidate the confounding effect, Pearson's χ 2 test and logistic regression models were used to correlate these characteristics with EGFR mutations in 426 NSCLC patients treated at our institutes. Of those 426 NSCLC patients, 47% were females, 57% were non-smokers and 84% had adenocarcinomas. The multivariate logistic regression analysis demonstrated that never-smoker status [odds ratio (OR)=3.49, 95% confidence interval (CI): 1.99-6.13; P<0.001)] and adenocarcinoma (OR=9.43, 95% CI 3.62-24.56; P<0.001) were associated with EGFR mutations; however, gender was not (OR=1.25, 95% CI: 0.73-2.15; P=0.416). Furthermore, gender was not associated with EGFR mutation subtypes (OR=1.19, 95% CI: 0.56-2.50; P=0.650). The frequency of EGFR mutations among females and males was not different in non-smokers (64.8 vs. 55.8%, P=0.204) or ever-smokers (27.8 vs. 24.2%, P=0.775). Therefore, if the assessment for EGFR mutation status was limited to non-smoking females with adenocarcinoma, up to 40% of the patients harboring EGFR mutations would be precluded from the benefit of EGFR inhibitor therapy. Our results indicated that gender is a confounding factor for EGFR mutations in NSCLC and suggested that gender may not be associated with tumorigenesis in NSCLC-harboring EGFR mutations.

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Section: Discussioncontrasting

confidence: 53%

“…Global statistics estimated that 15% of lung cancer cases in males and 53% in females are not associated with smoking. Furthermore, among the East Asian populations, 11-23% of male and 61-90% of female lung cancer patients are never-smokers (1)(2)(3)(4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Histological subtype and smoking status, but not gender, are associated with epidermal growth factor receptor mutations in non-small-cell lung cancer

Hsiao¹,

Lin

Chou

et al. 2013

Molecular and Clinical Oncology

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“…This result is supported by the findings of the IARC 8 and many previous papers, 10,11,13,18,[21][22][23]25,26,34 and accords with a summary risk of 1.24 obtained in a meta-analysis. 9 Because adenocarcinoma is the predominant lung cancer type in non-smoking women, 17,[42][43][44] and so the effects of passive smoking may be particularly relevant to it, we also carried out analyses by histological type. Results showed a clear association between adenocarcinoma and an increased risk from passive smoking from the husband.…”

Section: Discussionmentioning

confidence: 99%

Passive smoking and lung cancer in Japanese non‐smoking women: A prospective study

Kurahashi

Inoue²,

Liu³

et al. 2007

Intl Journal of Cancer

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Although smoking is a major cause of lung cancer, the proportion of lung cancer cases among Japanese women who never smoked is high. As the prevalence of smoking in Japan is relatively high in men but low in women, the development of lung cancer in nonsmoking Japanese women may be significantly impacted by passive smoking. We conducted a population-based prospective study established in 1990 for Cohort I and in 1993 for Cohort II. The study population was defined as all residents aged 40-69 years at the baseline survey. 28,414 lifelong non-smoking women provided baseline information on exposure to tobacco smoke from their husband, at the workplace and during childhood. Over 13 years of follow-up, 109 women were newly diagnosed with lung cancer, of whom 82 developed adenocarcinoma. Compared with women married to never smokers, hazard ratio (HR) [95% confidence interval (CI)] for all lung cancer incidence in women who lived with a smoking husband was 1.34 (95% CI 0.81-2.21). An association was clearly identified for adenocarcinoma (HR 2.03, 95% CI 1.07-3.86), for which dose-response relationships were seen for both the intensity (p for trend 5 0.02) and amount (p for trend 5 0.03) of the husband's smoking. Passive smoking at the workplace also increased the risk of lung cancer (HR 1.32, 95% CI 0.85-2.04). Moreover, a higher risk of adenocarcinoma was seen for combined husband and workplace exposure (HR 1.93, 95% CI 0.88-4.23). These findings confirm that passive smoking is a risk factor for lung cancer, especially for adenocarcinoma among Japanese women. ' 2007 Wiley-Liss, Inc.Key words: lung cancer; passive smoking; histological type; prospective study; Japanese non-smoking women In Japan, lung cancer has been the second leading cause of cancer death in women since the 1980s. 1 Although the majority of lung cancers can be attributed to cigarette smoking, 53% of all women with lung cancer world-wide are never smokers. 2,3 The proportion of Japanese female lung cancer patients who have never smoked is as high as 70%, 4 whereas the proportion of Japanese women aged 20 or more who smoke is only around 10%. 5 The major risk for lung cancer in Japanese women cannot therefore be attributed to smoking. Given that the urine of non-smokers exposed to passive smoking contains concentrations of carcinogenic N-nitroso compounds, which are specific to tobacco 6 and the smoking rate in Japanese men is high, at around 50%, 5 passive smoking might be an important risk factor for lung cancer in nonsmoking Japanese women.Since the publication of the first positive findings by Hirayama in Japan, many studies have investigated the relation between passive smoking and lung cancer in non-smoking women. 7 Recently, the International Agency for Research on Cancer (IARC) concluded that findings on the risk of lung cancer associated with environmental tobacco smoke were consistent. 8 Moreover, a meta-analysis of published studies estimated that the excess risk of lung cancer in non-smokers who lived with a smoker compared to those who live...

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“…Because smoking may be the worst prognostic factor in lung cancer, 10,11) differences in smoking habit prevalence could result in significant differences in survival outcome between genders.…”

Section: Female Gender Is An Independent Prognostic Factor In Non-smamentioning

confidence: 99%

Female Gender Is an Independent Prognostic Factor in Non-small-cell Lung Cancer: A Meta-analysis

Nakamura

Ando

Shinmyo

et al. 2011

Ann Thorac Cardiovasc Surg

120

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Purpose: It is not clear whether women with non-small-cell lung cancer (NSCLC) live significantly longer than men. Thus, we conducted a meta-analysis of published studies to quantitatively compare NSCLC survival data between genders. Materials and Methods: A MEDLINE Web search for computer-archived bibliographic data regarding overall survival differences between genders was performed. DerSimonian-Laird random effects analysis was used to estimate the pooled hazard ratio (HR). Results: We selected 39 articles as appropriate data sources, involving 86 800 patients including 32 701 women and 54 099 men. Combined HRs for women vs. men in studies using univariate and multivariate analyses respectively were 0.79 (p <0.0001) and 0.78 (p <0.0001). Pooled HRs for 3 study subgroups having (1) fewer than 30% stage I cases, (2) fewer than 50% adenocarcinoma cases, and (3) statistical adjustment for smoking status all indicated the survival advantage of women. Conclusion: This meta-analysis of published data concerning NSCLC patients indicated significantly better survival for women.

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Never-Smokers With Lung Cancer: Epidemiologic Evidence of a Distinct Disease Entity

Cited by 328 publications

References 29 publications

Histological subtype and smoking status, but not gender, are associated with epidermal growth factor receptor mutations in non-small-cell lung cancer

Histological subtype and smoking status, but not gender, are associated with epidermal growth factor receptor mutations in non-small-cell lung cancer

Passive smoking and lung cancer in Japanese non‐smoking women: A prospective study

Female Gender Is an Independent Prognostic Factor in Non-small-cell Lung Cancer: A Meta-analysis

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