บทบาทของธาตุเหล็กฮีมต่อการเกิดมะเร็งลำไส้ใหญ่ที่มีการกลายพันธุ์ของยีน APC และกลยุทธ์ทางเลือกในการป้องกันมะเร็งลำไส้ใหญ่
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บทคัดย่อ
ในปี 2020 มะเร็งลำไส้ใหญ่และทวารหนักเป็นมะเร็งที่พบมากเป็นอันดับสามและเป็นสาเหตุอันดับสองของการเสียชีวิตจากโรคมะเร็งทั่วโลก การกลายพันธุ์ของยีน adenomatous polyposis coli (APC) เป็นหนึ่งในปัจจัยของการเกิดมะเร็งผ่านการรบกวนสัญญาณ Wnt โดยธาตุเหล็กฮีม (heme iron) ซึ่งเป็นส่วนประกอบหลักของเนื้อแดงสามารถกระตุ้นภาวะเครียดทางออกซิเดชันและการอักเสบเรื้อรัง ปัจจัยทั้งสองเหนี่ยวนำให้เกิดการส่งสัญญาณ Wnt และส่งผลให้เซลล์มีการเจริญเติบโตผิดปกติ อย่างไรก็ตาม ความเป็นพิษต่อเซลล์ที่เกิดจากธาตุเหล็กฮีมไม่ส่งผลต่อเซลล์ที่มีการกลายพันธุ์ของยีน APC ทำให้ความเสี่ยงของการเกิดมะเร็งของเซลล์กลายพันธุ์เพิ่มขึ้น กลไกที่เกิดขึ้นได้แก่ การเปลี่ยนแปลงทางชีวภาพของสารจากปฏิกิริยาออกซิเดชันของลิพิดที่มีประสิทธิภาพมากขึ้น การเพิ่มการสังเคราะห์เอนไซม์ต้านอนุมูลอิสระผ่าน nuclear factor erythroid 2-related factor 2 (Nrf2) และการลดการแสดงออกของ heme oxygenase-1 กระตุ้นการอักเสบ นอกจากนี้ ธาตุเหล็กฮีมยังรบกวนสมดุลของจุลินทรีย์ในลำไส้ ทำให้เกิดการอักเสบเรื้อรังร่วมกับการเติบโตของเซลล์ที่เพิ่มมากขึ้น อนึ่ง เซลล์ที่มีการกลายพันธุ์ของยีน APC สามารถลดการตายของเซลล์โดยผ่านการรบกวนสัญญาณการอักเสบนิวเคลียร์แฟคเตอร์-แคปปาบี (nuclear factor kappa B) ด้วยเหตุนี้ เพื่อลดความเสี่ยงของการเกิดมะเร็งลำไส้ใหญ่โดยเฉพาะผู้ที่มีการกลายพันธุ์ของยีน APC ควรจำกัดการบริโภคอาหารที่อุดมด้วยธาตุเหล็กฮีม และอาจพิจารณาเพิ่มการบริโภคผลิตภัณฑ์อาหารเสริมที่ให้ประโยชน์ในการต้านอนุมูลอิสระ ต้านการอักเสบ และการปรับสมดุลของจุลินทรีย์ในลำไส้
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