The mean age was 55.68 years (standard deviation was 13.06). Our patients developed the disease at an earlier age than other women in other studies [
6, 7
].
In our study, the percentage of never-smokers was 75 %. 14 % of patients had an environmental tobacco smoke exposure (the husband or another person in the family who smoke) and 11 % were reported personal smoking. In the majority of American and European reviews, most of the patients were current or ex-smokers [7–9]. Recently, approximately 23.1 % of men and 18.3 % of women in the United States have been cigarette smokers so far [10].
Tobacco does not explain all the women cases with lung cancer, because in this study, 75 % of patients were never smokers. Multiple factors such as environmental exposures, genetic mutations, hormonal factors, and some infections have also been implicated in the development of lung cancer in women who have never smoked [1]. A possible role of circulating steroid hormones particularly of oestrogens, in the etiology of lung cancer has been hypothesized [11]. It should be noted that oestrogen receptors have been detected on cancerous lung cells and estrogens induce the differentiation and maturation of the foetal lung [11–13]. Different studies have suggested that there is a potential protective effect of increased or prolonged estrogen exposure, others have found the opposite [14, 15].
Furthermore, a large meta-analysis reported a 24.5 % worldwide incidence of HPV in lung cancer, particularly in China [16] and recently, many Asian studies indicate that longer telomere length may increase lung cancer risk [17].
Studies evaluating gene environment interactions may provide important insights into carcinogenesis pathways of lung cancer in never smokers.
In European and American series, most cases of non-small cell lung cancer were diagnosed at a relatively advanced stage according to the TNM classification system [6]. In our population, proportion of non small cell lung cancer at stage IV was higher (82 %), 16 % of cases were at stage III and only 2 % were at stage II. This high percentage can be explained by the delay of diagnosis.
At the end of 1960s, changes in the frequency of different histological subtypes of lung cancer have been observed worldwide, with an increasing proportion of adenocarcinoma and a declining proportion of squamous cell carcinoma [18]. In our study, the proportion of adenocarcinoma among never and passive smokers was higher than that of squamous cell carcinoma (69.4 versus 30.6 %), while among women who were smokers, the most frequent histological type was squamous cell carcinoma (63.6 %). These results are almost similar to those reported in other studies. Adenocarcinoma represented 68.1 % in the Mayo Clinic’ study, 71 % in the Bennet’s series and 43.4 % in the Grivaux study [6, 9, 19].
Moreover, women’s 5-year relative survival rates have improved across nearly all stages with similar histologies, the benefit was more important in those with adenocarcinoma [20, 21]. In this study, adenocarcinoma was significantly associated with poorer survival [HR: 1.73 (95 % CI 1.05, 2.85); p = 0.03], while in a Radzikowska study published in Annals of Oncology 2002, the squamous cell carcinoma was a negative predictor of survival in univariate analysis (p = 0.008), but this result was no significant in multivariate analysis (p = 0.29) [7].
Lung cancer survival rates for non smokers have improved compared with those of smokers [22]. In this series, the Cox regression analysis showed that smoking and passive smoking were not significantly associated with survival [HR: 0.62 (95 % CI 0.31, 1.30); p = 0.19] [HR: 0.56 (95 % CI 0.29, 1.08); p = 0.08] respectively. Even though HR are neither statistically significant for smoking nor passive smoking, HR estimates seem to show a protective effect for tobacco smoking, which is highly unlikely. This may indicate some bias or confounding within the study population. However, the data does not allow additional analysis to understand these estimates.
This study had potential limitations, one of which was the retrospective nature of the analysis. Definitely, a case control study with healthy controls would have been methodologically more powerful.
