PM2.5 長期暴露與大腸直腸癌發生與存活之相關性

Abstract

背景：細懸浮微粒 (PM2.5) 已被確認為肺癌之致癌因子，PM2.5 與其他癌症之關聯性尚無定論。部分研究發現，PM2.5 之暴露可能導致大腸直腸癌發生風險與死亡風險的增加，然而目前研究缺乏以長期暴露資料評估 PM2.5 暴露對大腸直腸癌的影響。本研究結合全國性資料庫，建立大腸直腸癌患者於診斷前之長期暴露與診斷後之暴露評估，探討 PM2.5 長期暴露與大腸直腸癌發生與存活之相關性。 材料與方法：使用臺灣癌症登記資料庫，納入 1997 – 2022 年之新診斷大腸直腸癌病例，並計算年齡標準化發生率。使用環境部空氣品質監測站資料，結合中央氣象署署屬氣象站之氣象資料，以能見度建立 PM2.5 回推模型，回溯 1968 – 1993 年濃度，並以 PM2.5 / PM10 比率計算 1994 – 2004 年之 PM2.5 濃度，結合 1968 – 2004 年回溯資料與 2005 – 2023 年實測資料，建立臺灣 1968 – 2023 年 PM2.5濃度資料。使用所建立之 PM2.5 濃度資料，計算 1997 – 2022 年全國 PM2.5 30 年移動平均濃度，並以簡單線性迴歸評估全國 PM2.5 30 年移動平均濃度與全國 1997 – 2022 年大腸直腸癌發生率之相關性。以 2011 – 2022 年之新診斷大腸直腸癌病例與非肺腺癌病例進行病例 - 對照研究，以個人之診斷日期回推 30 年計算個人診斷前 30 年之平均 PM2.5 暴露濃度，使用多元邏輯斯迴歸模型，調整性別、年齡、BMI、飲酒與吸菸，計算診斷前 30 年之個人 PM2.5 暴露增加對大腸直腸癌之發生率比。針對診斷後 PM2.5 暴露對存活之效應，納入 1997 – 2018 年之大腸直腸癌病例，並追蹤至 2023 年 12 月 31 日，以診斷日期開始至追蹤期結束計算個人診斷後平均 PM2.5 暴露濃度，以 Kaplan-Meier 存活分析計算五年存活率，並使用 Cox 比例風險模型，以所調整之變項分為基本模型與完整模型，基本模型納入 1997 – 2018 年之病例，調整性別、年齡，並且進一步依全國性篩檢實施之 2004 年作為切點，將基本模型分為篩檢前模型 (1997 – 2003 年) 及篩檢後模型 (2004 – 2018 年)。完整模型納入 2011 – 2018 年之病例，進一步調整癌症期別、腫瘤原發部位、治療、飲酒、吸菸、BMI、腸阻塞，以計算 PM2.5 暴露濃度下降一個標準差之大腸直腸特異性死亡及全因死亡風險比。 結果：臺灣之 PM2.5 30年移動平均濃度自1997 年的 25.7 µg/m3，下降至 2022 年的 26.1 µg/m3；大腸直腸癌標準化發生率則自 1997 年的每十萬人口 29.0，在 2004 年全國性篩檢計畫實施後，急遽上升至 2017 年的每十萬人口 60.7，後下降至 2022 年的 51.1，且兩者具顯著正相關，PM2.5 濃度每上升 1 µg/m3，發生率每十萬人口增加 8.48。在病例 - 對照研究中，大腸直腸癌病例之診斷前 30 年平均暴露濃度為 35.0 µg/m3，非肺腺癌病例為 34.5 µg/m3；PM2.5 暴露每上升 10 µg/m3，大腸直腸癌與非肺腺癌之發生率比顯著上升至 1.09，年齡每增加 1 歲，發生率比顯著下降至 0.99，BMI 每增加 1 kg/m2，發生率顯著增加 3 %，且飲酒者相較於非飲酒者，具有較高之發生率比。臺灣的 PM2.5 年平均濃度自 1997 年的 30.9 µg/m3 下降至 2023 年的 13.4 µg/m³。大腸直腸癌五年存活率自 1997 年的 50 %，持續上升至 2018 年的 61 %。在納入 1997 – 2018 年病例的基本 Cox 比例風險模型中，病例於 1997 – 2004 年的 PM2.5 暴露是以 PM2.5 / PM10 之比率回推，2005 – 2023 年則使用空品測站實測資料，存活病例之 PM2.5 暴露濃度區間為 8.1 - 47.9 µg/m³，死亡病例則為 4.8 - 107.9 µg/m³。PM2.5暴露濃度每下降 8.7 µg/m3，與大腸直腸特異性存活提升 22 %、全因存活提升 33 % 顯著相關，且在全國性篩檢實施前後，PM2.5 暴露濃度下降可分別使大腸直腸特異性存活提升 42 % 及 34 %，全因存活可提升 23 % 及37 %；在納入 2011 – 2018 年病例的完整 Cox 比例風險模型中，病例之 PM 2.5 暴露皆以空品測站實測資料計算，存活病例之 PM2.5 暴露濃度區間為 8.1 - 42.1 µg/m³，死亡病例為 4.8 - 107.9 µg/m³。PM2.5 每下降 6.5 µg/m3，與大腸直腸特異性存活提升 30 % 顯著相關，與全因存活提升 31 % 顯著相關，顯示 PM2.5 暴露降低對於大腸直腸癌存活改善具潛在效益。 結論：本研究發現，診斷前 30 年之 PM2.5 暴露的增加與大腸直腸癌發生的增加顯著正相關，且大腸直腸癌病例診斷後 PM2.5 暴露的降低與存活改善具顯著正相關，並且此結果獨立於篩檢、治療以及其他預後因素。本研究結果支持應將空氣汙染防制納入癌症預防與健康促進政策，以降低大腸直腸癌疾病負擔並提升共共健康。

Background: Fine particulate matter (PM2.5) has been identified as a carcinogen for lung cancer, while its associations with other cancers remain inconclusive. Some studies have suggested that PM2.5 exposure may increase the risk of colorectal cancer (CRC) incidence and mortality. However, current research remains limited, particularly regarding evaluations of long-term PM2.5 exposure. This study utilized a nationwide database to estimate long-term exposure both before and after diagnosis among CRC cases, with the aim of investigating the associations between long-term PM2.5 exposure and CRC incidence and survival. Material and Methods: Data were obtained from the Taiwan Cancer Registry, and CRC cases diagnosed from 1997 to 2022 were recruited. Age-standardized incidence rates were calculated. PM2.5 concentration data from 1968 to 1993 were back-cast using model based on visibility, developed from air quality monitoring data by the Ministry of Environment and meteorological data from the Central Weather Administration. PM2.5 concentrations between 1994 – 2004 were estimated using PM2.5/PM10 ratios. And combined with PM2.5 monitoring data from 2005 – 2023 to construct a nationwide PM2.5 concentration dataset spanning 1968 – 2023. We calculated 30-year moving averages of PM2.5 (1997–2022) and assessed their association with CRC incidence using simple linear regression. A case–referent study was conducted using newly diagnosed CRC cases and non-adenocarcinoma lung cancer cases from 2011 to 2022. Individual-level PM2.5 exposure over 30 years prior to diagnosis was estimated. Multiple logistic regression model was used to estimate incidence rate ratios (IRR) associated with individual 30-year PM2.5 exposure, and adjusted for sex, age, BMI, alcohol consumption, and smoking. We included CRC cases diagnosed from 1997 to 2018 and follow-up until December 31, 2023. Individual-level average PM2.5 exposure after diagnosis was calculated from the date of diagnosis to the end of follow-up. 5-year survival rate were estimated using Kaplan-Meier analysis. Cox proportional hazards models were used to estimate hazard ratios for colorectal-specific and all-cause mortality associated with a one standard deviation decrease in PM2.5 exposure. The basic model included cases diagnosed from 1997 to 2018 and was adjusted for sex and age; it was further stratified by the implementation of the national screening program (pre-screening: 1997–2003; post-screening: 2004–2018). The comprehensive model included cases from 2011 to 2018 and adjusted for cancer stage, tumor location, treatment, alcohol consumption, smoking, BMI, and bowel obstruction. Results: From 1997 to 2022, the 30-year moving average of PM2.5 concentrations in Taiwan changed from 25.7 to 26.1 µg/m³. Age-standardized incidence rate of CRC increased markedly from 29.0 per 100,000 in 1997 to a peak of 60.7 in 2017 following the launch of the nationwide screening program in 2004, then declined to 51.1 in 2022. PM2.5 concentrations were significantly positively associated with CRC incidence; each 1 µg/m³ increase in PM2.5 was linked to an 8.48 per 100,000 increase in CRC incidence. In the case–referent study, a 10 µg/m³ increase in PM2.5 exposure was significantly associated with an IRR of 1.09 for CRC compared to non-adenocarcinoma lung cancer. Additionally, each 1-year increase in age was associated with a significant decrease in IRR to 0.99, while each kg/m² increase in BMI was associated with 3% increase in incidence. And alcohol drinkers exhibited higher incidence rate compared to non-drinkers. Annual PM2.5 concentrations in Taiwan declined from 30.9 µg/m³ in 1997 to 13.4 µg/m³ in 2023, while 5-year survival rates for CRC increased from 50% in 1997 to 61% in 2018. In the basic Cox model for cases diagnosed between 1997 and 2018, PM2.5 exposure from 1997 to 2004 was estimated based on the PM2.5/PM10 ratio, while exposure from 2005 to 2023 was derived from monitoring data. PM2.5 exposure levels ranged from 8.1 – 47.9 µg/m³ among survivors and 4.8 – 107.9 µg/m³ among death cases. An 8.7 µg/m³ decrease in PM2.5 was significantly associated with 22% improvement in colorectal-specific survival and 33% in all-cause survival. In pre-screening (1997 - 2003) and post-screening (2004 - 2018) periods, reductions in PM2.5 were associated with 42% and 34% improvements in colorectal-specific survival, and 23% and 37% in all-cause survival, respectively. In the comprehensive Cox model for cases diagnosed between 2011 and 2018, PM2.5 exposure was entirely based on monitoring data. Survivor exposures ranged from 8.1 – 42.1 µg/m³, and 4.8 – 107.9 µg/m³ among death cases. Each 6.5 µg/m³ decrease in PM2.5 was significantly associated with 30% increase in colorectal-specific survival and 31% increase in all-cause survival. These findings indicate that reduction in PM2.5 exposure may provide additional survival benefits for CRC patients. Conclusion: An increase in PM2.5 exposure during the 30 years prior to diagnosis was significantly associated with a higher risk of CRC incidence. Furthermore, a reduction in PM2.5 exposure after diagnosis was significantly associated with improved survival, independent of screening, treatment, or other prognostic factors. These findings support the incorporation of air pollution control into cancer prevention and health promotion policies to reduce the burden of CRC and enhance public health.