Family history of cancer predicts endometrial cancer risk independently of Lynch Syndrome: Implications for genetic counselling
| Autor: | Michael A Bowman, Amanda B. Spurdle, Tracy A. O'Mara, Alison Brand, Michael A. Quinn, Andreas Obermair, Martin K. Oehler, Yen Y. Tan, Judy Kirk, Sharon E. Johnatty, Penelope Blomfield, Rhiannon J. Walters, Yee Leung, Daniel D. Buchanan, Penelope M. Webb |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology Proband medicine.medical_specialty Family Cancer History Genetic counseling Genetic Counseling 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Humans Genetic Predisposition to Disease Family history Medical History Taking Second-degree relative Gynecology business.industry Endometrial cancer Case-control study Australia Obstetrics and Gynecology Middle Aged medicine.disease Colorectal Neoplasms Hereditary Nonpolyposis Lynch syndrome Endometrial Neoplasms 030104 developmental biology Logistic Models 030220 oncology & carcinogenesis Case-Control Studies Female business |
| Zdroj: | Gynecologic oncology. 147(2) |
| ISSN: | 1095-6859 |
| Popis: | Objective To determine endometrial cancer (EC) risk according to family cancer history, including assessment by degree of relatedness, type of and age at cancer diagnosis of relatives. Methods Self-reported family cancer history was available for 1353 EC patients and 628 controls. Logistic regression was used to quantify the association between EC and cancer diagnosis in ≥1 first or second degree relative, and to assess whether level of risk differed by degree of relationship and/or relative's age at diagnosis. Risk was also evaluated for family history of up to three cancers from known familial syndromes (Lynch, Cowden, hereditary breast and ovarian cancer) overall, by histological subtype and, for a subset of 678 patients, by EC tumor mismatch repair (MMR) gene expression. Results Report of EC in ≥1 first- or second-degree relative was associated with significantly increased risk of EC ( P =3.8×10 −7 ), independent of lifestyle risk factors. There was a trend in increasing EC risk with closer relatedness and younger age at EC diagnosis in relatives ( P Trend =4.43×10 −6 ), and with increasing numbers of Lynch cancers in relatives ( P Trend ≤0.0001). EC risk associated with family history did not differ by proband tumor MMR status, or histological subtype. Reported EC in first- or second-degree relatives remained associated with EC risk after conservative correction for potential misreported family history (OR 2.0; 95% CI, 1.24–3.37, P =0.004). Conclusion The strongest predictor of EC risk was closer relatedness and younger EC diagnosis age in ≥1 relative. Associations remained significant irrespective of proband MMR status, and after excluding MMR pathogenic variant carriers, indicating that Lynch syndrome genes do not fully explain familial EC risk. |
| Databáze: | OpenAIRE |
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