Essential meiotic endonuclease 1 homolog 1 （EME1） is a key DNA repair protein that participates in the rec- ognition and repair of DNA double-strand breaks. Deficiency of the EME1 gene can lead to spontaneous genomi...Essential meiotic endonuclease 1 homolog 1 （EME1） is a key DNA repair protein that participates in the rec- ognition and repair of DNA double-strand breaks. Deficiency of the EME1 gene can lead to spontaneous genomic instability and thus contribute to tumorgenesis. We hypothesized that the exon variants of EME1 confer genetic susceptibility to breast cancer. In a case-control study of 748 breast cancer patients and 778 normal controls, we analyzed the association between two exon variants of EME! （i.e.,Ile350Thr： rs12450550T 〉 C and Glu69Asp： rs3760413T 〉 G） and breast cancer risk. We found that compared to the common lie/lie genotype, the Thr variant genotypes （Thr/lle ＋ Thr/Thr） conferred a 1.47-fold increased risk of breast cancer （OR=1.47, 95% CI=I. 13-1.92）. The variant Ile350Thr was also associated with early onset of breast cancer （r = -0.116, P = 0.002）. The mean age of onset was 44.4 years for Thr/Thr genotype carders and 46.5 years for Thr/lle genotype carriers, which was significantly lower than that （49.4 years） for Ile/Ile genotype carriers （P = 0.006）. Moreover, no significant as- sociation was observed between the Glu69Asp variant and breast cancer risk. Our findings suggest that the EME1 variant Ile350Thr contributes to an increased risk and early onset of breast cancer.展开更多
In this post-genomic era, more and more susceptibility loci of many possible genetic diseases are published. As our knowledge about these susceptibility loci is limited and partial, we should be very careful and respo...In this post-genomic era, more and more susceptibility loci of many possible genetic diseases are published. As our knowledge about these susceptibility loci is limited and partial, we should be very careful and responsible when patients seek genetic counseling about these possible genetic diseases. We should apply Confucius' s principle about knowledge and information to genetic conseling, and tell the truth to our patients about what we know and what we do not know. Like many other cancers, breast cancer is a very complicated, multifactorial disease; genetic factors, lifestyles and eating habits, environmental factors, and viral infections might be involved in breast cancer; hence, it is difficult to figure out the real etiology of breast cancer. It is not crystal clear that a person who carries mutations of the breast cancer 1, early onset and/or breast cancer 2, early onset genes would eventually get breast cancer in her/his lifetime. No person should undergo a preventive double mastectomy, unless we know the etiology of breast cancer someday.展开更多
基金supported by the National Natural Science Foundation of China (grants 30671813,30872178,81072366,and 81273149)Guangdong Provincial High Level Experts Grants (No.2010-79)+1 种基金Changjiang Scholars and Innovative Research Team in University grant (No.IRT0961)Guangdong Natural Science Foundation Team Grant (No.10351012003000000 to Dr.J.Lu)
文摘Essential meiotic endonuclease 1 homolog 1 （EME1） is a key DNA repair protein that participates in the rec- ognition and repair of DNA double-strand breaks. Deficiency of the EME1 gene can lead to spontaneous genomic instability and thus contribute to tumorgenesis. We hypothesized that the exon variants of EME1 confer genetic susceptibility to breast cancer. In a case-control study of 748 breast cancer patients and 778 normal controls, we analyzed the association between two exon variants of EME! （i.e.,Ile350Thr： rs12450550T 〉 C and Glu69Asp： rs3760413T 〉 G） and breast cancer risk. We found that compared to the common lie/lie genotype, the Thr variant genotypes （Thr/lle ＋ Thr/Thr） conferred a 1.47-fold increased risk of breast cancer （OR=1.47, 95% CI=I. 13-1.92）. The variant Ile350Thr was also associated with early onset of breast cancer （r = -0.116, P = 0.002）. The mean age of onset was 44.4 years for Thr/Thr genotype carders and 46.5 years for Thr/lle genotype carriers, which was significantly lower than that （49.4 years） for Ile/Ile genotype carriers （P = 0.006）. Moreover, no significant as- sociation was observed between the Glu69Asp variant and breast cancer risk. Our findings suggest that the EME1 variant Ile350Thr contributes to an increased risk and early onset of breast cancer.
文摘In this post-genomic era, more and more susceptibility loci of many possible genetic diseases are published. As our knowledge about these susceptibility loci is limited and partial, we should be very careful and responsible when patients seek genetic counseling about these possible genetic diseases. We should apply Confucius' s principle about knowledge and information to genetic conseling, and tell the truth to our patients about what we know and what we do not know. Like many other cancers, breast cancer is a very complicated, multifactorial disease; genetic factors, lifestyles and eating habits, environmental factors, and viral infections might be involved in breast cancer; hence, it is difficult to figure out the real etiology of breast cancer. It is not crystal clear that a person who carries mutations of the breast cancer 1, early onset and/or breast cancer 2, early onset genes would eventually get breast cancer in her/his lifetime. No person should undergo a preventive double mastectomy, unless we know the etiology of breast cancer someday.
