Lifetime Hormonal Exposure and Risk of Lung Cancer in Women: Results From a French Population-Based Case-Control Study (The WELCA Study).
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BACKGROUND: With 2 million new cases annually, lung cancer is among the most frequent and the leading cause of cancer-related death worldwide. Incidence trends differ by gender, decreasing in men but increasing in women, partly due to later tobacco uptake. However, biological differences may also contribute, including the potential role of estrogen exposure. This study aimed to investigate the influence of lifetime hormonal exposure on lung cancer risk in women. METHODS: WELCA is a multicenter population-based case-control study conducted in Ile-de-France between 2014 and 2017 among women aged 18-75 years. The study included 716 cases of incident primary lung cancer and 756 controls frequency-matched by age and area of residence. Information was collected through standardized questionnaires on lifestyle factors, occupational history, reproductive history, and use of exogenous hormones. Odds-ratios (OR) and confidence intervals (CI) were estimated using multivariable logistic regression models. RESULTS: A later age at last pregnancy (≥ 33 vs. ≤ 28 years) and ever use of hormonal contraceptives was associated with a lower risk of lung cancer (OR = 0.60; 0.42-0.85 and OR = 0.57; 0.39-0.84, respectively). However, a later age at cessation of the pill use was associated with an increased risk (≥ 39 vs. ≤ 30 years: OR = 1.46; 1.06-2.03). Finally, a longer reproductive lifespan was inversely associated with lung cancer (≥ 39 vs. ≤ 36 years: OR = 0.69; 0.50-0.95). CONCLUSION: These findings suggest lifetime hormonal exposure may influence lung cancer risk in women. They support the hypothesis of a hormonally mediated pathway and highlight the need for further studies on sex-specific lung cancer risk.