Roszak Andrzej, Lianeri Margarita, Jagodziński Paweł P
Department of Radiotherapy and Gynecological Oncology, Greater Poland Cancer Center, Poznań, Poland.
Genet Test Mol Biomarkers. 2012 Aug;16(8):841-5. doi: 10.1089/gtmb.2011.0308. Epub 2012 Apr 5.
The natural killer group 2, member D (NKG2D) receptor is mainly situated on the surface of NK and CD8(+) αβ T cells that are involved in the defense against viral agents and in cancer immunosurveillance. The G>A transition (Thr72Ala) (rs2255336) located in the NKG2D region encoding the transmembrane part of this receptor has been associated with decreased functionality of NK and T cells.
Using polymerase chain reaction-restriction fragment length polymorphisms, we examined the NKG2D Thr72Ala polymorphism in patients with cervical cancer (n=353) and controls (n=366) in a Polish population.
We observed an increased frequency of Thr/Thr or/and Thr/Ala genotypes in controls compared with all patients with cervical cancer; however, these differences were not significant. We found a significantly increased frequency of the NKG2D 72Thr allele in controls than in all patients (odds ratio [OR]=0.7410 [95% confidence intervals (CI)=0.5683-0.9662, p=0.0265]). Moreover, stratification of patients based on cancer stage showed a significant increase in the Thr/Thr genotype frequency (OR=0.3086 [95% CI=0.09097-1.047, p=0.0461]), as well as in the Thr/Thr and Thr/Ala genotype frequency (OR=0.4504 [95% CI=0.2891-0.7018, p=0.0003]), in controls compared with patients with cervical cancer in stages III and IV. The frequency of the NKG2D 72Thr allele was also significantly increased in controls as compared with patients in stage III and IV cancer (OR=0.4699 [95% CI=0.3170-0.6967, p=0.0001]).
Our studies may suggest that the women with cervical cancer bearing the NKG2D 72Thr gene variant might be protected against progression to advanced stages of this cancer.
自然杀伤细胞2族D成员（NKG2D）受体主要位于自然杀伤细胞和CD8(+)αβT细胞表面，参与抗病毒防御和癌症免疫监视。位于编码该受体跨膜部分的NKG2D区域的G>A转换（苏氨酸72丙氨酸）（rs2255336）与自然杀伤细胞和T细胞功能降低有关。
我们使用聚合酶链反应-限制性片段长度多态性方法，在波兰人群的宫颈癌患者（n=353）和对照组（n=366）中检测了NKG2D苏氨酸72丙氨酸多态性。
我们观察到，与所有宫颈癌患者相比，对照组中苏氨酸/苏氨酸或/和苏氨酸/丙氨酸基因型的频率有所增加；然而，这些差异并不显著。我们发现，对照组中NKG2D 72苏氨酸等位基因的频率显著高于所有患者（优势比[OR]=0.7410[95%置信区间（CI）=0.5683-0.9662，p=0.0265]）。此外，根据癌症分期对患者进行分层后发现，与III期和IV期宫颈癌患者相比，对照组中苏氨酸/苏氨酸基因型频率显著增加（OR=0.3086[95%CI=0.09097-1.047，p=0.0461]），苏氨酸/苏氨酸和苏氨酸/丙氨酸基因型频率也显著增加（OR=0.4504[95%CI=0.2891-0.7018，p=0.0003]）。与III期和IV期癌症患者相比，对照组中NKG2D 72苏氨酸等位基因的频率也显著增加（OR=0.4699[95%CI=0.3170-0.6967，p=0.0001]）。
我们的研究可能表明，携带NKG2D 72苏氨酸基因变体的宫颈癌女性可能对癌症进展至晚期具有保护作用。
