PURPOSE: Lower urinary tract symptoms and obesity are prominent health problems. Low birth weight increases the adult risk of adiposity and insulin resistance, which may increase sympathetic activity and potentially lower urinary tract symptoms. Results of obesity and lower urinary tract symptoms studies are conflicting, and low birth weight and lower urinary tract symptoms relationships have not been investigated. MATERIALS AND METHODS: This cross-sectional study examines lower urinary tract symptoms, body measures, activity, birth weight and lifestyle data collected by questionnaire from 1997 to 1998. Overall 27,858 men were analyzed and odds ratios calculated after excluding those with cancer, cerebrovascular accident, diabetes and incomplete information. RESULTS: After adjustment for age, activity level, smoking, alcohol, coffee intake and body mass index, a significant positive association was seen between abdominal obesity (waist-to-hip ratio) and moderate to severe lower urinary tract symptoms. The risks of moderate to severe and severe lower urinary tract symptoms were 22% (95% CI 1.09-1.37) and 28% (95% CI 1.01-1.63) higher, respectively, for the top vs the lowest abdominal obesity quartile. The risk of nocturia (twice or more per night) was 1.16 (95% CI 1.02-1.33) in men in the top compared to the bottom waist-to-hip ratio quartile. Men with low birth weight (less than 2,500 gm) had a 61% (95% CI 1.12-2.30) higher risk of severe lower urinary tract symptoms compared to men with normal birth weight (2,500 to 3,999 gm). Men in the top waist-to-hip ratio quartile who had low birth weight had twice the risk of severe lower urinary tract symptoms (95% CI 1.29-3.02) compared to men with normal birth weight and in the lowest waist-to-hip ratio quartile. CONCLUSIONS: Low birth weight and abdominal adiposity are associated with increased risk of moderate to severe lower urinary tract symptoms in adults. Further investigations are needed to determine if decreases in obesity can ameliorate lower urinary tract symptoms.
BACKGROUND: Recently identified associations of prostate cancer risk with several genes involved in innate immunity support a role of inflammation in the etiology of prostate cancer. Considering inflammation is regulated by a complex system of gene products, we hypothesize sequence variants in many other genes of this pathway are associated with prostate cancer. METHODS: We evaluated 9,275 SNPs in 1,086 genes of the inflammation pathway using a MegAllele genotyping system among 200 familial cases and 200 unaffected controls selected from a large Swedish case-control population (CAPS). RESULTS: We found that significantly more than the expected numbers of SNPs were significant at a nominal P-value of 0.01, 0.05, and 0.1, providing overall support for our hypothesis. The excess was largest when using a more liberal nominal P-value (0.1); we observed 992 significant SNPs compared with the 854 significant SNPs expected by chance, and this difference was significant based on a permutation test (P = 0.0025). We also began the effort of differentiating true associated SNPs by selecting a small subset of significant SNPs (N = 26) and genotyped these in an independent sample of approximately 1,900 CAPS1 subjects. We were able to confirm 3 of these 26 SNPs. It is expected that many more true associated SNPs will be confirmed among the 992 significant SNPs identified in our pathway screen. CONCLUSIONS: Our study provides the first objective support for an association between prostate cancer and multiple modest-effect genes in inflammatory pathways.
BACKGROUND: Findings from epidemiologic studies of the effect of dairy foods (mainly milk) on the risk of bladder cancer have been inconsistent. OBJECTIVE: We aimed to examine the association between the intake of cultured milk and other dairy foods and the incidence of bladder cancer in a prospective, population-based cohort. DESIGN: We prospectively followed 82,002 Swedish women and men who were cancer-free and who completed a 96-item food-frequency questionnaire in 1997. Incident cases of bladder cancer were identified in the Swedish cancer registries. RESULTS: During a mean follow-up of 9.4 y, 485 participants (76 women and 409 men) were diagnosed with bladder cancer. Total dairy intake was not significantly associated with risk of bladder cancer [> or =7.0 servings/d compared with or =2 servings/d) compared with the lowest category (0 serving/d) were 0.62 (95% CI: 0.46, 0.85; P for trend = 0.006) in women and men combined, 0.55 (95% CI: 0.25, 1.22; P for trend = 0.06) in women, and 0.64 (95% CI: 0.46, 0.89; P for trend = 0.03) in men. The intake of milk or cheese was not associated with bladder cancer risk. CONCLUSION: These findings suggest that a high intake of cultured milk may lower the risk of developing bladder cancer.
Epidemiologic studies on diabetes and body size in relation to risk of bladder cancer have yielded inconsistent results. We examined prospectively the associations between a history of diabetes, height, weight, body mass index and waist circumference, and the incidence of bladder cancer in the Cohort of Swedish Men, a prospective study of 45,906 men aged 45-79 years at baseline. During follow-up from 1998 through December 2007, 414 incident cases of bladder cancer were ascertained. A history of diabetes was not associated with risk of bladder cancer (multivariate rate ratio=1.16; 95% confidence interval=0.81-1.64). Similarly, no associations were observed for height, weight, body mass index or waist circumference. These findings in men do not support a role for diabetes, height or excess body mass in the aetiology of bladder cancer.
BACKGROUND: The causes of prostate cancer are poorly understood, but genetic factors may be more important than for many other malignancies, and dietary phytoestrogens may be protective. Because phytoestrogens bind tightly to the estrogen receptor-beta, we conducted an epidemiologic investigation of synergistic effects between phytoestrogen intake and estrogen receptor-beta gene polymorphisms. METHODS: We performed a population-based case-control study in Sweden. All participants reported their phytoestrogen intake and donated a blood sample. We identified four haplotype-tagging single nucleotide polymorphisms (htSNPs) and genotyped these htSNPs in 1314 prostate cancer patients and 782 controls. Odds ratios were estimated by multivariate logistic regression. Interactions between phytoestrogen intake and estrogen receptor-beta SNPs on prostate cancer risk were evaluated considering both multiplicative and additive effect scales. RESULTS: We found a significant multiplicative interaction (P = 0.04) between dietary intake of phytoestrogens and a promoter SNP in the estrogen receptor-beta gene (rs 2987983-13950), but not with any of the three other htSNPs (P = 0.11, 0.69, 0.85). Among carriers of the variant promoter alleles, we found strong inverse associations with increasing intake of total phytoestrogens (odds ratio for highest vs. lowest quartile = 0.43; P for trend
BACKGROUND: The majority of prostate cancers harbor gene fusions of the 5'-untranslated region of the androgen-regulated transmembrane protease serine 2 (TMPRSS2) promoter with erythroblast transformation-specific transcription factor family members. The common fusion between TMPRESS2 and v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) is associated with a more aggressive clinical phenotype, implying the existence of a distinct subclass of prostate cancer defined by this fusion. METHODS: We used complementary DNA-mediated annealing, selection, ligation, and extension to determine the expression profiles of 6144 transcriptionally informative genes in archived biopsy samples from 455 prostate cancer patients in the Swedish Watchful Waiting cohort (1987-1999) and the United States-based Physicians(') Health Study cohort (1983-2003). A gene expression signature for prostate cancers with the TMPRSS2-ERG fusion was determined using partitioning and classification models and used in computational functional analysis. Cell proliferation and TMPRSS2-ERG expression in androgen receptor-negative (NCI-H660) prostate cancer cells after treatment with vehicle or estrogenic compounds were assessed by viability assays and quantitative polymerase chain reaction, respectively. All statistical tests were two-sided. RESULTS: We identified an 87-gene expression signature that distinguishes TMPRSS2-ERG fusion prostate cancer as a discrete molecular entity (area under the curve = 0.80, 95% confidence interval [CI] = 0.792 to 0.81; P
Fruit and vegetable consumption has been inconsistently associated with risk of bladder cancer. We used data from a prospective population-based cohort study of 82,002 Swedish women and men to examine the association between fruit and vegetable consumption and bladder cancer incidence. Diet was assessed with a validated food frequency questionnaire. During a mean follow-up of 9.4 years, 485 incident cases of bladder cancer were identified in the Swedish cancer registries. We found no statistically significant association between intakes of total fruits and vegetables, total fruits, or total vegetables and bladder cancer risk after adjustment for age, sex, education, and cigarette smoking. The multivariate rate ratios (95% confidence intervals) comparing the highest with the lowest quartile of intake were 0.80 (0.60-1.05) for total fruits and vegetables, 0.93 (0.69-1.25) for fruits, and 0.89 (0.67-1.19) for vegetables. Likewise, no associations were observed for citrus fruits, cruciferous vegetables, or green leafy vegetables. The associations did not differ by sex or smoking status. In conclusion, findings from this prospective study suggest that fruit and vegetable intakes are not likely to be appreciably associated with the risk of bladder cancer.
PURPOSE: Although prostate-specific antigen (PSA) is the best biomarker for predicting prostate cancer, its predictive performance needs to be improved. Results from the Prostate Cancer Prevention Trial revealed the overall performance measured by the areas under curve of the receiver operating characteristic at 0.68. The goal of the present study is to assess the ability of genetic variants as a PSA-independent method to predict prostate cancer risk. EXPERIMENTAL DESIGN: We systematically evaluated all prostate cancer risk variants that were identified from genome-wide association studies during the past year in a large population-based prostate cancer case-control study population in Sweden, including 2,893 prostate cancer patients and 1,781 men without prostate cancer. RESULTS: Twelve single nucleotide polymorphisms were independently associated with prostate cancer risk in this Swedish study population. Using a cutoff of any 11 risk alleles or family history, the sensitivity and specificity for predicting prostate cancer were 0.25 and 0.86, respectively. The overall predictive performance of prostate cancer using genetic variants, family history, and age, measured by areas under curve was 0.65 (95% confidence interval, 0.63-0.66), significantly improved over that of family history and age (0.61%; 95% confidence interval, 0.59-0.62; P = 2.3 x 10(-10)). CONCLUSION: The predictive performance for prostate cancer using genetic variants and family history is similar to that of PSA. The utility of genetic testing, alone and in combination with PSA levels, should be evaluated in large studies such as the European Randomized Study for Prostate Cancer trial and Prostate Cancer Prevention Trial.
The etiologic role of physical activity in prostate cancer development is unclear. We assessed the association between lifetime total physical activity and prostate cancer risk in a Swedish population-based case-control study comprising 1,449 incident prostate cancer cases and 1,118 unaffected population controls. Information regarding physical activity was obtained via a self-administered questionnaire assessing occupational, household, and recreational activity separately at various ages throughout an individual's lifetime. Clinical data (TNM-classification, Gleason sum and PSA) was obtained from linkage to the National Prostate Cancer Registry. Overall, we observed no association between lifetime total physical activity and prostate cancer risk (odds ratio [OR] = 1.04, 95% confidence interval [CI] = 0.77-1.41 for > or =49.7 vs.
CONTEXT: The epidemiological evidence that fatty fish consumption may be associated with the lower risk of several cancers is not consistent and no studies of renal cell carcinoma (RCC) exist. OBJECTIVE: To examine the association between fatty and lean fish consumption and risk of RCC in women. DESIGN, SETTING, AND PARTICIPANTS: The Swedish Mammography Cohort, a population-based prospective cohort study of 61,433 women aged 40 to 76 years without previous diagnosis of cancer at baseline (March 1, 1987-December 14, 1990). Participants filled in a food frequency questionnaire at baseline and in September 1997. MAIN OUTCOME MEASURE: Incident renal cell carcinoma. RESULTS: During a mean of 15.3 years (940,357 person-years) of follow-up between 1987 and 2004, 150 incident RCC cases were diagnosed. After adjustment for potential confounders, an inverse association of fatty fish consumption with the risk of RCC was found (P for trend = .02), but no association was found with lean fish consumption. Compared with no consumption, the multivariate rate ratio (RR) was 0.56 (95% confidence interval [CI], 0.35-0.91) for women eating fatty fish once a week or more. Compared with women consistently reporting no fish consumption, the multivariate RR was 0.26 (95% CI, 0.10-0.67) for those women reporting consistent consumption of fatty fish at baseline and 1997 (based on a subset of 36 664 women who filled in the baseline and 1997 questionnaires, with 40 incident RCC cases during the 1998-2004 follow-up period). CONCLUSION: Our study suggests that consumption of fatty fish may reduce the occurrence of RCC in women.