台灣女性乳癌與第二原發肺癌之關聯性: 全國人口之世代研究

Association between breast cancer and second primary lung cancer among female population in Taiwan: A nationwide population-based cohort study

林汎文(Fan-Wen Lin)

指導教授 ： 魏正宗

共同指導教授 ： 葉名焮(Ming-Hsin Yeh)

中山醫學大學/醫學院/醫學研究所/碩士(2021年)

https://doi.org/10.6834/csmu202100173

摘要

研究目的
在臨床中偶然觀察到台灣的乳癌女性患者常伴隨發生第二原發肺癌，過去已有數篇文獻發表關於乳癌與肺癌的相關性，然而針對亞洲族群的研究相對稀少。目前唯一一篇以台灣全國人口為對象之研究結論便支持這項論點，即乳癌與肺癌確實存在特殊關連性，該研究經數據分析後僅顯示兩種癌症在診斷時間差距六個月內(不分先後)才具統計學上意義，更推斷基因變異或許是造成雙癌症的主因。然而上述研究並未考量共病及特定生活習慣可能導致潛在干擾。另一方面，根據臨床經驗，第二原發性肺癌往往是在乳癌追蹤數月甚至數年後才被診斷，故我們想探究當兩種癌症的診斷時間差大於六個月時是否還能保有關聯性。

研究方法及資料
本研究以台灣健保資料庫(NHIRD)為基礎，將2000年至2012年期間十八歲以上且住院第一診斷碼為乳癌(ICD-9-CM 174)的病人收案為病例組，對照組為無癌症之病人，兩組間以年齡(每五歲一個間距)及診斷年份進行頻率配對，收案數為1:4。事件結果為肺癌(ICD-9-CM 162)。而被視為潛在干擾因子的共病包含冠狀動脈疾病(ICD-9-CM 410-414)、中風(ICD-9-CM 430-438)、高血壓(ICD-9-CM 401-405)、糖尿病(ICD-9-CM 250)、慢性阻塞性肺病(ICD-9-CM 490, 492, 496)、高血脂(ICD-9-CM 272)、結核病(ICD-9-CM 01)、睡眠障礙(ICD-9-CM 307.4, 780.5)以及焦慮症(ICD-9-CM 300)。我們使用多變數Cox迴歸分析來分析兩組病人罹患肺癌之風險比(hazard ratios)，並透過傾向分數配對(propensity score matching)進行敏感度分析。所有統計分析皆由SAS statistical software, version 9.4 (SAS Institute Inc., Cary, NC)這項軟體執行。

研究結果
本研究由健保資料庫共納入94451名乳癌病人作為疾病組及377804非癌病人作為對照組。依據年齡及多項共病進行分層分析後，乳癌病人相對於其他無乳癌的病人確實有較高的風險罹患第二原發肺癌，特別是年輕族群(年齡介於20到49歲aHR = 2.10, 95% CI = 1.71-2.58 / 年齡介於50到64歲aHR = 1.35, 95% CI = 1.15-1.58)和無其他共病的族群(aHR = 1.92, 95% CI = 1.64-2.23)。

結論與建議
乳癌病人罹患第二原發肺癌之風險顯著高於沒有的乳癌病人，特別是年輕族群及無其他共病的族群。除了遺傳基因，我們推測長期PM2.5暴露可能是同時誘發兩種癌症的危險因子，因而空氣汙染議題應獲得更多重視。相關議題仍需要更多研究佐證，例如PM2.5造成癌化之致病機轉、不同分型的乳癌及肺癌之間的關聯、其他可能造成乳癌和肺癌的未確認因子等。

關鍵字

台灣女性乳癌 ； 第二原發肺癌 ； 台灣女性

並列摘要

Objective
A special association between breast cancer and second primary lung cancer in Taiwanese women has been discovered not only in clinical practice but also in a large population-based study. We investigate the association between breast cancer and second primary lung cancer in Taiwanese women after taking age and several comorbidities into account.

Material and Methods
This study was conducted from the National Health Insurance Research Database (NHIRD) from Taiwan National Health Insurance (NHI). Patients who aged more than 18 years old and hospitalized with the first diagnosis of breast cancer (ICD-9-CM 174) during 2000 to 2012 were enrolled in the case group. Patients who were cancer free were frequency-matched with case group by age (every 5 year span) and index year. The ratio of case group to control group is 1:4. The event as the outcome in this study was lung cancer (ICD-9-CM 162). The comorbidities viewed as important confounding factors included coronary artery disease (ICD-9-CM 410-414), stroke (ICD-9-CM 430-438), hypertension (ICD-9-CM 401-405), diabetes (ICD-9-CM 250), chronic obstructive pulmonary disease (ICD-9-CM 490, 492, 496), hyperlipidemia (ICD-9-CM 272), tuberculosis (ICD-9-CM 01), sleep disorder (ICD-9-CM 307.4, 780.5) and anxiety (ICD-9-CM 300). We estimated hazard ratios (HRs), adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for risk of lung cancer in case and control group by using Cox proportional hazard models. Sensitivity analysis was also done by using propensity score matching. All statistical analyses were performed using SAS statistical software, version 9.4 (SAS Institute Inc., Cary, NC).

Results
There were 94,451 breast cancer patients as case group and 377,804 patients as control group in this study. After stratified by age and comorbidities, patients with breast cancer had significantly higher risk of lung cancer compared to patients without breast cancer, particularly for those who aged between 20 and 49 years (aHR = 2.10, 95% CI = 1.71-2.58), 50 and 64 years (aHR = 1.35, 95% CI = 1.15-1.58), and without any comorbidity (aHR = 1.92, 95% CI = 1.64-2.23).

Conclusion and Suggestion
Patients with breast cancer had significantly higher risk of developing second primary lung cancer compared to patients without breast cancer, particularly in younger groups and in those who without any comorbidities. Aside from inherited genotypes, long-term exposure to PM2.5, as a potential risk factor of both breast and lung cancers, is supposed to increase public awareness. Further studies are necessary given the fact that different subtypes of breast cancer and lung cancer as well as other unrecognized etiologies may play vital roles in both cancers’ development. Besides, the mechanism of how PM2.5 leads to carcinogenesis remains unclear and needs further exploration.

並列關鍵字

Breast cancer ； Second primary lung cancer ； Taiwanese women

參考文獻

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