Hongyao Yu1, Otto Hemminki2, Asta Försti3, Kristina Sundquist4, Kari Hemminki3. 1. Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany. Electronic address: h.yu@dkfz.de. 2. Department of Urology, Helsinki University Hospital, Helsinki, Finland; Cancer Gene Therapy Group, Faculty of Medicine, University of Helsinki, Helsinki, Finland. 3. Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany; Center for Primary Health Care Research, Lund University, Malmö, Sweden. 4. Center for Primary Health Care Research, Lund University, Malmö, Sweden; Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Abstract
BACKGROUND: Family risks for urinary tract cancers (excluding kidney cancers) are known, but less is known about whether rare urinary tract cancer subtypes are also familial and if urinary tract cancers share familial risk for other (discordant) cancers. OBJECTIVE: To investigate the impact of family history on urinary tract cancers (International Classification of Diseases version 7 code 181) and discordant cancers. DESIGN, SETTING, AND PARTICIPANTS: The Swedish Family-Cancer Database, the largest family data set in the world, was used to assess familial risks between 86 058 patients with urinary tract cancers and patients with other cancers between 1958 and 2015. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A Poisson regression model was used to generate relative risks (RRs). RESULTS AND LIMITATIONS: Some 7.0% of patients with urinary tract cancers had a parent or sibling diagnosed with the same cancer, yielding an RR of 1.81 (95% confidence interval [CI] 1.68-1.94). As novel familial findings, we also found that ureter (RR 1.62, 95% CI 1.04-2.53) and transitional cell in situ tumors (RR 2.04, 95% CI 1.49-2.80) were associated with urinary tract cancers. The most consistent discordant familial associations of urinary tract cancers were with smoking-related sites of cancer: lung, stomach, and kidney. Internally consistent familial associations not related to smoking were found for endometrial and thyroid cancers. Familial associations with urinary tract cancers were also found for rare anal, female genital, and cervical cancers. The main limitation was a lack of data on smoking. CONCLUSIONS: Smoking-related cancers were associated with urinary tract cancer. We speculate that familial clustering of endometrial and thyroid cancers with urinary tract cancers may be ascribed to obesity. PATIENT SUMMARY: Diagnosis of bladder cancer in a close family member may be a sign of higher risk among other family members. Patients and family members should be told that bladder cancer is smoking-related and they should be counseled to recognize blood in urine as a possible early sign.
BACKGROUND: Family risks for urinary tract cancers (excluding kidney cancers) are known, but less is known about whether rare urinary tract cancer subtypes are also familial and if urinary tract cancers share familial risk for other (discordant) cancers. OBJECTIVE: To investigate the impact of family history on urinary tract cancers (International Classification of Diseases version 7 code 181) and discordant cancers. DESIGN, SETTING, AND PARTICIPANTS: The Swedish Family-Cancer Database, the largest family data set in the world, was used to assess familial risks between 86 058 patients with urinary tract cancers and patients with other cancers between 1958 and 2015. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A Poisson regression model was used to generate relative risks (RRs). RESULTS AND LIMITATIONS: Some 7.0% of patients with urinary tract cancers had a parent or sibling diagnosed with the same cancer, yielding an RR of 1.81 (95% confidence interval [CI] 1.68-1.94). As novel familial findings, we also found that ureter (RR 1.62, 95% CI 1.04-2.53) and transitional cell in situ tumors (RR 2.04, 95% CI 1.49-2.80) were associated with urinary tract cancers. The most consistent discordant familial associations of urinary tract cancers were with smoking-related sites of cancer: lung, stomach, and kidney. Internally consistent familial associations not related to smoking were found for endometrial and thyroid cancers. Familial associations with urinary tract cancers were also found for rare anal, female genital, and cervical cancers. The main limitation was a lack of data on smoking. CONCLUSIONS: Smoking-related cancers were associated with urinary tract cancer. We speculate that familial clustering of endometrial and thyroid cancers with urinary tract cancers may be ascribed to obesity. PATIENT SUMMARY: Diagnosis of bladder cancer in a close family member may be a sign of higher risk among other family members. Patients and family members should be told that bladder cancer is smoking-related and they should be counseled to recognize blood in urine as a possible early sign.