Eliane Kellen

Sequence variant on 8q24 confers susceptibility to urinary bladder cancer

We conducted a genome-wide SNP association study on 1,803 urinary bladder cancer (UBC) cases and 34,336 controls from Iceland and The Netherlands and follow up studies in seven additional case-control groups (2,165 cases and 3,800 controls). The strongest association was observed with allele T of rs9642880 on chromosome 8q24, 30 kb upstream of MYC (allele-specific odds ratio (OR) = 1.22; P = 9.34 × 10−12). Approximately 20% of individuals of European ancestry are homozygous for rs9642880[T], and their estimated risk of developing UBC is 1.49 times that of noncarriers. No association was observed between UBC and the four 8q24 variants previously associated with prostate, colorectal and breast cancers, nor did rs9642880 associate with any of these three cancers. A weaker signal, but nonetheless of genome-wide significance, was captured by rs710521[A] located near TP63 on chromosome 3q28 (allele-specific OR = 1.19; P = 1. 15 × 10−7).

Genetic variation in the prostate stem cell antigen gene PSCA confers susceptibility to urinary bladder cancer

We conducted a genome-wide association study on 969 bladder cancer cases and 957 controls from Texas. For fast-track validation, we evaluated 60 SNPs in three additional US populations and validated the top SNP in nine European populations. A missense variant (rs2294008) in the PSCA gene showed consistent association with bladder cancer in US and European populations. Combining all subjects (6,667 cases, 39,590 controls), the overall P-value was 2.14 × 10−10 and the allelic odds ratio was 1.15 (95% confidence interval 1.10–1.20). rs2294008 alters the start codon and is predicted to cause truncation of nine amino acids from the N-terminal signal sequence of the primary PSCA translation product. In vitro reporter gene assay showed that the variant allele significantly reduced promoter activity. Resequencing of the PSCA genomic region showed that rs2294008 is the only common missense SNP in PSCA. Our data identify rs2294008 as a new bladder cancer susceptibility locus.

A meta-analysis on the association between bladder cancer and occupation

To date, many epidemiological studies have been conducted to examine the association between occupation and bladder cancer incidence. However, results from these studies often have been inconsistent, and significant associations have rarely been found, possibly owing to the lack of adequate statistical power in these studies. This meta-analysis summarizes the relevant literature regarding occupation and bladder cancer incidence to increase the statistical power to detect associations. The Medline and Embase databases were searched to retrieve epidemiological studies published up until May 2008. Individual risk estimates for subjects with an employment history in the occupation of interest were extracted from each included publication. For each occupation, a summary relative risk (SRR) was calculated by means of a random effects model. Significantly increased risks with an SRR greater than 1.20 were identified for miners [SRR=1.31, 95% confidence interval (CI) 1.09–1.57], bus drivers (SRR=1.29, 95% CI 1.08–1.53), rubber workers (SRR=1.29, 95% CI 1.06–1.58), motor mechanics (SRR=1.27, 95% CI 1.10–1.46), leather workers (SRR=1.27, 95% CI 1.07–1.49), blacksmiths (SRR=1.27, 95% CI 1.02–1.58), machine setters (SRR=1.24, 95% CI 1.09–1.42), hairdressers (SRR=1.23, 95% CI 1.11–1.37) and mechanics (SRR=1.21, 95% CI 1.12–1.31). In conclusion, the studies reviewed provide consistent support for a small but significant increased risk of bladder cancer among workers in these nine occupations. Although the relative risk of bladder cancer associated with these occupations is small, the public health impact may be significant, considering the substantial number of people who were and are employed in these occupations.

A meta-analysis on depression and subsequent cancer risk

BackgroundThe authors tested the hypothesis that depression is a possible factor influencing the course of cancer by reviewing prospective epidemiological studies and calculating summary relative risks.MethodsStudies were identified by computerized searches of Medline, Embase and PsycINFO. as well as manual searches of reference lists of selected publications. Inclusion criteria were cohort design, population-based sample, structured measurement of depression and outcome of cancer known for depressed and non-depressed subjectsResultsThirteen eligible studies were identified. Based on eight studies with complete crude data on overall cancer, our summary relative risk (95% confidence interval) was 1.19 (1.06–1.32). After adjustment for confounders we pooled a summary relative risk of 1.12 (0.99–1.26).No significant association was found between depression and subsequent breast cancer risk, based on seven heterogeneous studies, with or without adjustment for possible confounders. Subgroup analysis of studies with a follow-up of ten years or more, however, resulted in a statistically significant summary relative risk of 2.50 (1.06–5.91).No significant associations were found for lung, colon or prostate cancer.ConclusionThis review suggests a tendency towards a small and marginally significant association between depression and subsequent overall cancer risk and towards a stronger increase of breast cancer risk emerging many years after a previous depression.

VALIDATION OF THE IMMIDIET FOOD FREQUENCY QUESTIONNAIRE IN AN ADULT BELGIAN POPULATION: A REPORT FROM THE BELGIAN CASE-CONTROL STUDY ON BLADDER CANCER RISK

Abstract We evaluated the performance of the IMMIDIET food frequency questionnaire (FFQ) used to collect dietary data for the Belgian case-control study on bladder cancer. Thirty-seven men and women aged 50 years and older were recruited from the University Hospital in Leuven, Belgium. Participants completed the IMMIDIET FFQ, a 7-day diet diary and a 24-hour diet recall. Median intakes and inter-quartile ranges were calculated for 27 foods and nutrients from each dietary assessment method. All dietary factors were log-transformed and adjusted for energy using the nutrient density method. Pearson correlation coefficients were used to compare the different dietary assessment methods. Bland-Altman plots were also used to assess levels of agreement between the dietary methods. Energy, fruit and vegetable intake estimates were higher from the IMMIDIET FFQ compared with the two reference methods. The highest deattenuated correlations between the FFQ and 7-day diary were meat (0.58), bread (0.44), fruit (0.38) and fish (0.38). The highest deattenuated correlations between the FFQ and 24-hour recall were for fruit (0.72), fat (0.48), alcohol (0.44), cholesterol (0.42), monounsaturated fatty acid (0.42) and polyunsaturated fatty acid (0.41). Generally, correlation was lower for the micro-nutrients except for phosphorus (0.42), vitamin C (0.41) and calcium (0.40). The IMMIDIET FFQ is an appropriate instrument to measure usual dietary intake for the Belgian case-control study on bladder cancer risk. Further investigation of nutritional assessment methods is necessary.