Zhu Ming, Chen Xiaoxiang, Zhang Huan, Xiao Nong, Zhu Changdong, He Qiong, Guo Wenwen, Cai Zhenming, Shen Hongbing, Wang Yaping
Department of Medical Genetics, Nanjing University School of Medicine, Nanjing, China.
Asian Pac J Cancer Prev. 2011;12(6):1451-5.
A common polymorphism of the AluYb8 insertion in the MUTYH gene (AluYb8MUTYH), which led to the increase of oxidative DNA damage and acceleration of chronic diseases, was previously detected. Considering the relationship between carcinogenesis and oxidative stress, an investigation was held on whether the common variant of the MUTYH gene increases the risk for gastric and breast cancers.
The AluYb8MUTYH allele frequencies of 545 breast cancer patients and 762 gastric cancer patients were analyzed and compared with that of the healthy control group using the Chi-square test. The binary logistic regression model was used to examine the association between the polymorphism genotypes and cancer risk. Genomic DNA specimens from the investigated population were tested by polymerase chain reaction in agarose gel electrophoresis. According to the insertion absence or presence of the variant segment, the patterns for the AluYb8MUTYH genotypes were classified as a homozygous of absence/absence (A/A) and presence/presence (P/P) or a heterozygous of absence/presence (A/P).
The variant allele frequency (insertion present, P) was inclined to be enhanced in breast cancer patients as compared with the normal female controls (46.8% versus 43.3%), and also, in gastric cancer patients, as compared with the general normal controls (45.1% versus 43.9%). However, a significantly different P allele frequency was only detected between the early-onset breast cancer patients (<55 years old) and their counterpart female controls (46.6% versus 40.9%, p=0.042; OR=1.26, 95% CI, 1.01-1.56), as well as between the early-onset gastric cancer patients and their respective controls (49.2% versus 41.3%, p=0.042; OR, 1.37; 95% CI, 1.02-1.85). Comparisons on the genotypes of AluYb8MUTYH show that this variation of MUTYH has also a significantly higher prevalence in the early-onset cancer patients, either in breast or gastric cancer patients, than that in their counterpart controls.
The AluYb8MUTYH allele frequency can be associated with the early-onset breast and gastric cancer in the Chinese population. Probably, there is importance in screening the carriers with the susceptibility alleles to evaluate their risk of breast and gastric cancer for further research.
先前检测到MUTYH基因中AluYb8插入的一种常见多态性（AluYb8MUTYH），其导致氧化DNA损伤增加和慢性疾病加速。考虑到致癌作用与氧化应激之间的关系，对MUTYH基因的常见变异体是否会增加胃癌和乳腺癌风险进行了一项研究。
分析了545例乳腺癌患者和762例胃癌患者的AluYb8MUTYH等位基因频率，并使用卡方检验将其与健康对照组进行比较。采用二元逻辑回归模型检验多态性基因型与癌症风险之间的关联。通过聚合酶链反应在琼脂糖凝胶电泳中对研究人群的基因组DNA样本进行检测。根据变异片段的插入缺失情况，将AluYb8MUTYH基因型模式分为缺失/缺失纯合子（A/A）和存在/存在纯合子（P/P）或缺失/存在杂合子（A/P）。
与正常女性对照组相比，乳腺癌患者的变异等位基因频率（存在插入，P）有升高趋势（46.8%对43.3%），与一般正常对照组相比，胃癌患者的变异等位基因频率也有升高趋势（45.1%对43.9%）。然而，仅在早发性乳腺癌患者（<55岁）与其对应的女性对照组之间检测到显著不同的P等位基因频率（46.6%对40.9%，p = 0.042；OR = 1.26，95%CI，1.01 - 1.56），以及早发性胃癌患者与其各自对照组之间（49.2%对41.3%，p = 0.042；OR，1.37；95%CI，1.02 - 1.85）。对AluYb8MUTYH基因型的比较表明，MUTYH的这种变异在早发性癌症患者（无论是乳腺癌还是胃癌患者）中的患病率也显著高于其对应的对照组。
AluYb8MUTYH等位基因频率可能与中国人群的早发性乳腺癌和胃癌相关。可能有必要筛查携带易感等位基因的个体，以评估他们患乳腺癌和胃癌的风险，以供进一步研究。
