Kour Akeen, Sambyal Vasudha, Guleria Kamlesh, Singh Neeti Rajan, Uppal Manjit Singh, Manjari Mridu, Sudan Meena
Guru Nanak Dev University, Department of Human Genetics, Human Cytogenetics Laboratory, Amritsar, Punjab, India.
Sri Guru Ram Das Institute of Medical Sciences and Research, Vallah,Department of Surgery, Amritsar, Punjab, India.
Genet Mol Biol. 2020 May 20;43(2):e20190014. doi: 10.1590/1678-4685-GMB-2019-0014. eCollection 2020.
The polymorphic variants of BRCA1, which lead to amino acid substitutions, have a known pathogenic role in breast cancer. The present study investigated in North Indian breast cancer patients the association of risk with four reported pathogenic variants of BRCA1: c.190T>C (p.Cys64Arg), 1307delT, g.5331G>A (p.G1738R) and c.2612C>T (p.Pro871Leu). Genotyping was done by PCR-RFLP method in 255 clinically confirmed breast cancer patients and 255 age and gender matched healthy individuals. For c.190T>C, 1307delT and g.5331G>A, all the patients and controls had the wild-type genotype indicating no association with breast cancer risk. For c.2612C>T polymorphism, the frequency of the CC, CT, and TT genotypes was 14.5 vs 15.7%, 59.6 vs 53.7% and 25.9 vs 30.6% in breast cancer patients and controls respectively. The frequency of heterozygotes (CT genotype) was higher in cases than controls but the difference was not statistically significant. Genetic model analysis showed no association of the four analyzed BRCA1 variants with breast cancer risk with any model. The studied variants were not associated with the risk of breast cancer in Punjab, North west India, suggesting a need for further screening of other BRCA1 variants. It is the first reported study on these 4 variants from India.
BRCA1的多态性变体可导致氨基酸替换，在乳腺癌中具有已知的致病作用。本研究在北印度乳腺癌患者中调查了BRCA1的四种已报道致病变体与风险的关联：c.190T>C（p.Cys64Arg）、1307delT、g.5331G>A（p.G1738R）和c.2612C>T（p.Pro871Leu）。采用PCR-RFLP方法对255例临床确诊的乳腺癌患者和255例年龄及性别匹配的健康个体进行基因分型。对于c.190T>C、1307delT和g.5331G>A，所有患者和对照均具有野生型基因型，表明与乳腺癌风险无关联。对于c.2612C>T多态性，CC、CT和TT基因型在乳腺癌患者和对照中的频率分别为14.5%对15.7%、59.6%对53.7%和25.9%对30.6%。杂合子（CT基因型）的频率在病例中高于对照，但差异无统计学意义。遗传模型分析显示，四种分析的BRCA1变体与任何模型的乳腺癌风险均无关联。在印度西北部的旁遮普邦，所研究的变体与乳腺癌风险无关，这表明需要进一步筛查其他BRCA1变体。这是印度首次报道的关于这4种变体的研究。
