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Is Low FMR1 CGG Repeat Length in Males Correlated with Family History of BRCA-Associated Cancers? An Exploratory Analysis of Medical Records

  • Original Research
  • Published:
Journal of Genetic Counseling

Abstract

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.

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Acknowledgements

This work was conducted as a part of the degree requirements and training completed at the University of Wisconsin Genetic Counselor Training Program. This research was supported by the Centers for Disease Control and Prevention through the Association of University Centers on Disability (Marsha R. Mailick, PI). We would like to thank the Marshfield Personalized Medicine Research Project research team for providing access to data from the PMRP, and their ongoing efforts in gathering this invaluable data. We would also like to thank all of the men who have participated in the PMRP. Support was also provided by the Wisconsin State Laboratory of Hygiene and the Waisman Center Core Grant (U54 HD090256). Lastly, we would like to thank Amy Stettner, Erin Borchardt, and Laura Pfleger for their helpful feedback and discussions.

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Authors and Affiliations

  1. Department of Pediatrics, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA

    Hallee C. Adamsheck, Elizabeth M. Petty & Mei W. Baker

  2. CentraCare Health, St. Cloud, MN, USA

    Hallee C. Adamsheck

  3. Waisman Center, University of Wisconsin-Madison, Madison, WI, USA

    Jinkuk Hong & Marsha R. Mailick

  4. Wisconsin State Laboratory of Hygiene, Madison, WI, USA

    Mei W. Baker

  5. Center for Human Genetics, Marshfield Clinic Research Institute, Marshfield, WI, USA

    Murray H. Brilliant

Authors
  1. Hallee C. Adamsheck
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  2. Elizabeth M. Petty
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  3. Jinkuk Hong
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  4. Mei W. Baker
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  5. Murray H. Brilliant
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  6. Marsha R. Mailick
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Correspondence to Hallee C. Adamsheck.

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Conflict of Interest

Authors Hallee Adamsheck, Elizabeth Petty, Jinkuk Hong, Mei Baker, Murray Brilliant, and Marsha Mailick declare that they have no conflict of interest.

Human Studies and Informed Consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained by PMRP from all patients for being included in the study. Subjects were consented to genetic testing when enrolled in the PMRP and results of any testing will not be returned to research subjects.

Animal Studies

This article does not contain any studies with animals performed by any of the authors.

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Adamsheck, H.C., Petty, E.M., Hong, J. et al. Is Low FMR1 CGG Repeat Length in Males Correlated with Family History of BRCA-Associated Cancers? An Exploratory Analysis of Medical Records. J Genet Counsel 26, 1401–1410 (2017). https://doi.org/10.1007/s10897-017-0116-5

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  • DOI: https://doi.org/10.1007/s10897-017-0116-5

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