Familial and environmental interactions in bladder cancer risk

Abstract

In a population-based study of 2,982 bladder cancer patients and 5,782 controls in 10 geographic areas of the United States which was designed to assess the role of environmental risk factors, information was also obtained on the history of urinary tract cancer in first-degree relatives. A family history of urinary tract cancer significantly elevated the risk of bladder cancer [relative risk (RR) = 1.45], with higher risks observed among patients under age 45. The risks of bladder cancer associated with positive family history were generally higher among persons with suspected environmental exposures, particularly heavy cigarette smoking (RR = 10.7 among those who smoked 3 or more packs per day). Further studies of bladder cancer should incorporate biochemical and genetic probes to assess mechanisms of familial susceptibility and interactions with environmental factors.

Familial and genetic risk of transitional cell carcinoma of the urinary tract

“…The largest case-control study (2900 cases; 5684 controls) demonstrated a RR = 1.5 (95% CI 1.2-1.8). [17] Familial risks tended to be higher among males (a finding not consistent among studies), younger probands (< age 45) and smokers. [17,20] No significant differences in risk emerged when case-control and cohort studies were compared.…”

“…[17] Familial risks tended to be higher among males (a finding not consistent among studies), younger probands (< age 45) and smokers. [17,20] No significant differences in risk emerged when case-control and cohort studies were compared. Among the cohort studies, an analysis of the Mormon genealogy data base yielded a familial RR = 1.5 (95% CI 1.0-2.2); [16] the RR was 5.1 (95% CI 1.0-12.5) among probands <age 60.…”

“…Table 4 summarizes pertinent details of 9 case-control and 4 cohort studies in which family history of TCCUT was quantitatively evaluated as a bladder cancer risk factor. [12][13][14][15][16][17][18][19][20][21][22][23][24] These studies varied widely in sample size, quality of design and analysis, inclusion/exclusion of upper urinary tract sites, and the extent to which reported cancers were objectively documented, but are surprisingly similar in their estimated risk ratios. These range from 1.2 to 6.1 among male and female cases combined, with most of the results clustering between 1.4 and 1.9.…”

“…[2,7] Common variants in low-penetrance genes involved in the metabolism of environmental toxins have been shown to modify individual susceptibility to bladder carcinogens. [2] Furthermore, a genetic predisposition to bladder cancer is suggested by the occurrence of TCCUT in several Mendelian disorders [8][9][10][11], epidemiologic studies showing that a positive TCCUT family history increases bladder cancer risk [12][13][14][15][16][17][18][19][20][21][22][23][24], and a limited number of case reports describing multiple-case TCCUT families. [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] Therefore, both genetic and environmental factors play a role in the development of bladder and related urinary tract cancers.…”

Bladder cancer risk as modified by family history and smoking

“…Consistent with our results, which suggest a joint effect of smoking and family history, a 45% greater risk of bladder cancer among those who had a first-degree relative with cancer of the urinary tract was reported in a population-based case-control study that included 2982 patients with bladder cancer and a group of 5782 control participants (the United States National Bladder Cancer Study). 21 Moreover, the risk of bladder cancer was greatest among heavy cigarette smokers. The authors proposed incorporating both familial susceptibility and environmental factors into the risk assessment of bladder cancer in future studies.…”