Thapa Sunaina, Lalrohlui Freda, Ghatak Souvik, Zohmingthanga John, Lallawmzuali Doris, Pautu Jeremy L, Senthil Kumar Nachimuthu
Department of Biotechnology, Mizoram University, Aizawl, 796004, Mizoram, India.
Department of Pathology, Civil Hospital, Aizawl, 796001, Mizoram, India.
Breast Cancer. 2016 Jul;23(4):607-16. doi: 10.1007/s12282-015-0611-1. Epub 2015 Apr 21.
Mizoram has the highest incidence of cancer in India. Among women, breast cancer is most prevalent and the state occupies fifth position globally. The reason for high rate of cancer in this region is still not known but it may be related to ethnic/racial variations or lifestyle factors.
The present study aims to identify the candidate mitochondrial DNA (mtDNA) biomarkers-ND1and ATPase for early breast cancer diagnosis in Mizo population. Genomic DNA was extracted from blood samples of 30 unrelated breast cancer and ten healthy women. The mtNDI and mtATP coding regions were amplified by step-down PCR and were subjected to restriction enzyme digestion and direct sequencing by Sanger method. Subsequently, the results of the DNA sequence analysis were compared with that of the revised Cambridge Reference Sequence (rCRS) using Mutation Surveyor and MITOMAP.
Most of the mutations were reported and new mutations that are not reported in relationship with breast cancer were also found. The mutations are mostly base substitutions. The effect of non-synonymous substitutions on the amino acid sequence was determined using the PolyPhen-2 software. Statistical analysis was performed for both cases and controls. Odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated from logistic regression. High intake of animal fat and age at menarche was found to be associated with a higher risk of breast cancer in Mizo population.
Our results also showed that ATPase6 as compared to ATPase8 gene is far more predisposed to variations in Mizo population with breast cancer and this finding may play an important role in breast cancer prognosis.
米佐拉姆邦是印度癌症发病率最高的地区。在女性中，乳腺癌最为普遍，该邦在全球排名第五。该地区癌症高发的原因尚不清楚，但可能与种族/民族差异或生活方式因素有关。
本研究旨在鉴定用于米佐人群早期乳腺癌诊断的候选线粒体DNA（mtDNA）生物标志物——ND1和ATP酶。从30名无血缘关系的乳腺癌患者和10名健康女性的血样中提取基因组DNA.通过逐步递减PCR扩增mtNDI和mtATP编码区，并进行限制性内切酶消化和桑格法直接测序。随后，使用Mutation Surveyor和MITOMAP将DNA序列分析结果与修订的剑桥参考序列（rCRS）进行比较。
报告了大多数突变，还发现了与乳腺癌无关的新突变.这些突变大多为碱基置换。使用PolyPhen-2软件确定非同义置换对氨基酸序列 的影响。对病例组和对照组均进行了统计分析。通过逻辑回归估计优势比（OR）和95%置信区间（CI）.发现米佐人群中动物脂肪摄入量高和初潮年龄与乳腺癌风险较高有关。
我们的结果还表明，与ATP酶8基因相比，ATP酶6在患乳腺癌的米佐人群中更容易发生变异，这一发现可能在乳腺癌预后中起重要作用。
