Smoking Patterns and Their Association with Histological Subtypes in Lung Cancer Patients

Lung cancer remains the leading cause of cancer-related mortality worldwide. Tobacco smoking is the most significant etiological factor, yet smoking patterns and their impact on lung cancer subtypes differ across genders. While men have traditionally shown higher smoking rates, recent shifts in social norms have led to increased female exposure both directly and passively^1-4. Understanding how sex-specific smoking behaviors correlate with histological subtypes of lung cancer can provide valuable insights for risk stratification and targeted prevention strategies.

Ethics approval for this study was obtained from the Non-Interventional Clinical Research Ethics Committee of Tekirdağ Namık Kemal University (desicion no: 2025.64.03.22, date: 25.03.2025). A retrospective cohort study was conducted including 539 patients diagnosed with lung cancer between 2017 and 2024. Demographic variables included age, gender, and survival status. Smoking-related variables included smoking status (never, active, passive, ex-smoker) and cumulative exposure (pack-year history). Histological classification was based on pathology reports: squamous cell carcinoma (SCC), adenocarcinoma, small cell lung cancer (SCLC), and non-SCLC not otherwise specified. Passive smoking was defined as regular exposure to cigarette smoke at home or in the workplace, as reported by the patient and documented in the anamnesis section of the medical records. The presence or absence of passive smoking was retrospectively extracted from the physician’s notes. No objective quantification was available.

Statistical Analysis

Descriptive statistics were presented as means ± standard error of the mean for continuous variables and percentages for categorical data. ANOVA and chi-square tests were used to assess differences among groups. A p-value<0.05 was considered statistically significant.

Patient Characteristics

The study population had a mean age of 64.0±0.42 years. Males accounted for 84.8% (n=457) and females 15.2% (n=82). Mean age at diagnosis was 63.5±0.42 years, and the mean survival time following diagnosis was 11.4±1.53 months (Table 1).

Smoking Behavior by Sex

The overall smoking behavior differed significantly between the sexes. Active smoking was common in both groups (52.4% of females vs. 57.1% of males). However, females had markedly higher rates of never smoking (20.7% vs. 2.8%) and passive exposure (14.6% vs. 1.8%), while ex-smoking was more prevalent in males (38.3% vs. 12.2%) (Table 2). Mean pack-year exposure was significantly higher in males (49.92±1.09) than in females (43.19±3.23), despite the lower proportion of ex-smokers in the latter group.

Histological Subtype and Smoking Correlation

SCC was the most frequent subtype among males (38.6%) and showed the highest mean pack-year (53.01±1.75). In contrast, adenocarcinoma was slightly more common in females (36.6%) and had the lowest mean pack-year exposure (43.16±1.75) (Table 3 and 4).

ANOVA showed significant differences in mean pack-year history among subtypes (p=0.0016) (Table 4). The chi-square test confirmed a significant association between smoking status and histological subtype (p=0.0002).

This study reveals that sex differences in smoking behavior are not only statistically significant but also pathologically relevant, manifesting as distinct patterns in lung cancer histology. Women, although demonstrating markedly lower rates of active smoking compared to men, show significantly elevated levels of passive smoke exposure. This discrepancy suggests that indirect tobacco exposure may play a more pronounced etiological role in the female population than previously assumed⁵. Of particular concern is the disproportionately high incidence of SCLC among female patients a histological subtype recognized for its aggressive clinical course and poor prognosis. This observation raises the possibility that even non-direct smoking exposure may be sufficient to trigger the development of high-grade malignancies, particularly in biologically susceptible individuals.

Furthermore, the relatively higher prevalence of adenocarcinoma in women corresponds with findings from prior studies, which have consistently linked this histological subtype to lighter or indirect smoking habits. This pattern has led researchers to hypothesize that adenocarcinoma may arise through different carcinogenic pathways than SCC, including possible interactions with hormonal influences, such as estrogen receptors, or genetic predispositions unique to female patients^6-9.

In contrast, the data underscore that men, who have higher rates of both current and former smoking, also demonstrate significantly greater cumulative tobacco exposure as measured in pack-years. This increased exposure is paralleled by the predominance of SCC among male patients a subtype long known to be closely associated with heavy and prolonged smoking. The dose-response relationship observed here reinforces the carcinogenic potency of long-term tobacco consumption, particularly in the development of central airway tumors such as SCC^10-12.

Taken together, these findings highlight the critical importance of incorporating gender-specific smoking patterns into predictive models of lung cancer risk^7-9,13. Public health policies and clinical screening protocols should not only continue to target active smoking but also increase focus on mitigating passive smoke exposure, particularly in women. In the era of personalized medicine, such stratified approaches could enhance both early detection and prevention efforts by tailoring them to the unique risk profiles shaped by gender and tobacco exposure dynamics.

Study Limitations

This study is limited by its retrospective design and reliance on medical records for smoking history, which may introduce recall bias. The relatively small female sample size also restricts the power of gender-based comparisons. Additionally, passive smoking exposure was not objectively measured, and potential confounders such as occupational and environmental factors were not accounted for.

Sex plays a critical role in shaping smoking exposure patterns and their oncological consequences. Recognition of these differences is crucial for developing more precise screening and prevention strategies in lung cancer care. Future studies should explore biological underpinnings and psychosocial determinants influencing gender disparities in lung carcinogenesis.