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サイクリンD1 A870Gポリモルフィズムと進行 kolorektal がんとの関連
Loïc Le Marchand1, Ann Seifried, Annette Lum-Jones
1Etiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI 96813, USA. loic@crch.hawaii.edu
JAMA
|December 6, 2003
まとめ
CCND1 870Aアレルは,特に進行した段階で,結腸直腸がんのリスクの増加と関連しています. この遺伝子変異は,より重症な疾患の結果と関連している可能性があります.
科学分野:
- 遺伝学とゲノミクス
- がん生物学 がん生物学
- エピデミオロジー エピデミオロジー
背景:
- サイクリンD1 (CCND1) は,ヒトの腫瘍発育に関与する重要な細胞循環調節剤です.
- CCND1の過剰発現は,細胞増殖の増加と癌の予後が悪いことと相関しています.
- 共通のCCND1遺伝子ポリモルフィズム (A870G) は,タンパク質の安定性と機能に影響を与え,Aアレルはより長寿のタンパク質と関連しています.
研究 の 目的:
- CCND1 870Aアレルと結腸直腸がん (CRC) の関連性を調査する.
- CCND1 870AアレルとCRCのリスクと重症度の相関を特定する.
- CRC発現におけるCCND1 870Aアレルの潜在的な遺伝子用量効果を調査する.
主な方法:
- ハワイで,集団ベースの症例対照研究が行われました.
- この研究では,504例の結腸直腸がん症例と,多民族集団の624例の対照群を対象とした.
- CCND1 870A/Gポリモルフィズムのゲノタイプ化が行われ,遺伝子用量効果,がんステージ,およびサブサイトを分析した.
主要な成果:
- 遺伝子用量効果が観察され,GGと比較してGAの確率比は1.2で,AAの確率比は1.5であった.
- CCND1 870AアレルとCRCリスクの関連性は,地域性/遠隔性ステージの疾患 (ORs1.7と1.9,それぞれ) について,著しく強かった.
- Aアレルは,白人とネイティブハワイ人の参加者における高度なCRCと有意に関連しており,直腸がんとより強く関連していました.
結論:
- CCND1 870Aアレルは,結腸直腸がんの発症に寄与する可能性があります.
- このアレルは,特に,重度の罹病率と死亡率につながる結腸直腸がんの形態と関連しているようです.
- CCND1 870AアレルのCRCの病原性および予後における役割に関するさらなる研究が必要である.
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