復(fù)旦大學(xué)遺傳工程實(shí)驗(yàn)室盧大儒教授聯(lián)合美國(guó)研究人員在《癌癥》期刊撰文指出,，兩種基因的變異可能是導(dǎo)致中國(guó)人更易罹患肺癌的原因,。
研究人員此前認(rèn)為，ABCB1和ABCC1兩種基因的作用是去除肺部的致癌物質(zhì),，防止吸入毒素導(dǎo)致肺癌,。
在本次研究中，研究者分析了中國(guó)東南部500名肺癌患者和517名未患肺癌者的基因,，并在聲明中寫(xiě)道：“某些基因變異在肺癌患者身上發(fā)生的概率比未患癌癥者身上大得多,。”
在肺癌患者中,，31%的人ABCB1基因發(fā)生某種變異，27%的人ABCC1基因發(fā)生變異,。而非癌癥患者中,，這兩種基因發(fā)生變異的概率則分別只有15%和12%。
研究人員稱(chēng)：“ABCB1的變異尤其會(huì)使女性和60歲以下人群罹患癌癥的幾率升高,。它還與一種常見(jiàn)肺癌--腺癌（adenocarcinoma）直接相關(guān),。”（生物谷Bioon.com）
生物谷推薦原始出處：
Cancer 23 Dec 2008 DOI 10.1002/cncr.24042
Genetic susceptibility of lung cancer associated with common variants in the 3 untranslated regions of the adenosine triphosphate-binding cassette B1 (ABCB1) and ABCC1 candidate transporter genes for carcinogen export
Haijian Wang, PhD 1 2, Guangfu Jin, PhD 3, Haifeng Wang, PhD 4, Gaifen Liu, PhD 5, Ji Qian, MS 1, Li Jin, PhD 1, Qingyi Wei, MD, PhD 6, Hongbing Shen, MD, PhD 3, Wei Huang, MD, PhD 4, Daru Lu, PhD 1 *
1State Key Laboratory of Genetic Engineering, Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China
2The Simons Center for Systems Biology, School of Natural Sciences, Institute for Advanced Study, Princeton, New Jersey
3Department of Epidemiology and Biostatistics, Cancer Research Center, Nanjing Medical University, Nanjing, China
4Department of Genetics, Chinese National Human Genome Center at Shanghai, Shanghai, China
5Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, Groningen, the Netherlands
6Department of Epidemiology, the University of Texas M. D. Anderson Cancer Center, Houston, Texas
*Correspondence to Daru Lu, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China
ABSTRACT
BACKGROUND:
Tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NKK) is a well defined carcinogen that can induce lung cancer. Genetic polymorphisms in its disposition pathways could modify the risk of developing lung cancer. The authors of this report previously catalogued the sequence variations of the adenosine triphosphate-binding cassette B1 (ABCB1) and ABCC1 candidate transporter genes for carcinogen export in the Chinese population and screened out common variants with potential function in their 5 flanking and 3 untranslated regions. The objective of the current study was to test the hypothesis that these common variants are associated with lung cancer risk.
METHODS:
The genotyping analyses for 6 common regulatory variants (reference single-nucleotide polymorphism 4728709 [rs4728709] and rs2188524 in the 5 flanking region of ABCB1 and rs3842 in its 3untranslated region; rs3743527, rs212090, and rs212091 in the 3 untranslated region of ABCC1) was conducted in a case-control study of 500 patients with incident lung cancer and 517 cancer-free controls in a Chinese population.
RESULTS:
Compared with the wild adenosine/adenosine (A/A) genotype, the variant rs3842 genotype (adenosine/guanosine [A/G] + G/G) of ABCB1 was associated with a statistically significant increased risk of developing lung cancer (odds ratio [OR]. 1.36; 95% confidence interval [95% CI], 1.06-1.76). Also evident was the association between cancer susceptibility and the variant rs212090 genotype (adenosine/thymidine [A/T] + T/T) of ABCC1 (OR, 1.37; 95% CI, 1.03-1.83). Haplotype-based association analysis also emphasized that 2 common haplotypes carrying the culprit alleles of the 2 single-nucleotide polymorphisms were associated with an increased risk of cancer. In addition, stratification analysis demonstrated a remarkable association of ABCB1 rs3842 with the risk of cancer manifested in women (OR, 2.57; 95% CI, 1.36-4.85), in the histologic type of adenocarcinoma (OR, 1.42; 95% CI, 1.03-1.99), and in individuals aged <60 years (OR, 1.50; 95% CI, 1.05-2.14).
CONCLUSIONS:
The current study demonstrated that common polymorphisms in the 3 untranslated region of ABCB1 and ABCC1 may contribute to the etiology of lung cancer, providing further support for the hypothesis that genetic components in the metabolism and the disposition of NNK may modify the risk of lung cancer, especially in lung adenocarcinoma among women. Functional studies are warranted to elucidate whether aberrant expression and dysfunction of ABC transporters for carcinogen export may play a role in the development of lung cancer. Cancer 2009. ? 2008 American Cancer Society.
