Adamsheck Hallee C, Petty Elizabeth M, Hong Jinkuk, Baker Mei W, Brilliant Murray H, Mailick Marsha R
Department of Pediatrics, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.
CentraCare Health, St. Cloud, MN, USA.
J Genet Couns. 2017 Dec;26(6):1401-1410. doi: 10.1007/s10897-017-0116-5. Epub 2017 Jun 30.
The FMR1 gene has been studied extensively with regard to expansions and premutations, but much less research has focused on potential effects of low CGG repeat length. Previous studies have demonstrated that BRCA1/2 positive women are more likely to have an FMR1 genotype with one low CGG allele, and that women with both FMR1 alleles in the low CGG repeat range are more likely to have had breast cancer compared to women with normal numbers of CGG repeats. However, there has been no research as to whether low CGG repeat length impacts cancer risks in men. Therefore, this study aimed to examine cancer incidence and related risk factors in men with low CGG repeat length in the FMR1 gene. We utilized subject data from the Marshfield Personalized Medicine Research Project to compare cancer-related diagnoses between 878 males with low CGG repeat length (< 24 repeats) and 368 male controls with CGG repeats in the normal range (24 to 40 repeats). We utilized ICD-9 codes to examine various cancer diagnoses, family histories of cancer, other non-malignant neoplasms, cancer surveillance, and genetic susceptibility. Men with low CGG repeats were identified to have significantly higher rates of family history of any cancer type (p = 0.011), family history of any BRCA-associated cancer (p = 0.002), and specifically, family history of prostate cancer (p = 0.007). The mean number of BRCA-associated cancer diagnoses (breast, prostate, pancreatic, and melanoma) per individual in the low CGG group was slightly higher than that of the control group, with this difference trending toward significance (p = 0.091). Additionally, men with low CGG repeats had significantly higher rates of connective/soft tissue neoplasms (p = 0.026). Additional research is needed to replicate the observations reported in this preliminary exploratory study, particularly including verification of ICD-9 codes and family history by a genetic counselor.
FMR1基因在扩增和前突变方面已得到广泛研究，但针对低CGG重复长度潜在影响的研究要少得多。先前的研究表明，BRCA1/2阳性女性更有可能拥有一个低CGG等位基因的FMR1基因型，并且与CGG重复次数正常的女性相比，两个FMR1等位基因均处于低CGG重复范围的女性患乳腺癌的可能性更大。然而，尚无关于低CGG重复长度是否会影响男性癌症风险的研究。因此，本研究旨在检查FMR1基因中CGG重复长度较低的男性的癌症发病率及相关风险因素。我们利用了马什菲尔德个性化医学研究项目的受试者数据，比较了878名CGG重复长度较低（<24次重复）的男性和368名CGG重复次数在正常范围（24至40次重复）的男性对照之间的癌症相关诊断。我们使用ICD - 9编码来检查各种癌症诊断、癌症家族史、其他非恶性肿瘤、癌症监测和遗传易感性。结果发现，CGG重复次数低的男性患任何癌症类型的家族史发生率显著更高（p = 0.011），患任何BRCA相关癌症的家族史发生率显著更高（p = 0.002），具体而言，患前列腺癌的家族史发生率显著更高（p = 0.007）。低CGG组中每人BRCA相关癌症诊断（乳腺癌、前列腺癌、胰腺癌和黑色素瘤）的平均数量略高于对照组，且这种差异有显著趋势（p = 0.091）。此外，CGG重复次数低的男性结缔组织/软组织肿瘤的发生率显著更高（p = 0.026）。需要进一步的研究来重复这项初步探索性研究中报告的观察结果，特别是需要遗传咨询师对ICD - 9编码和家族史进行核实。
