Debra T. Silverman

Background: Processed meat and unprocessed red meat are considered carcinogenic and ‘probably carcinogenic’ to humans, respectively, but findings for bladder cancer remain inconsistent. Objectives: We assessed associations between processed meat and unprocessed red meat intake and bladder cancer risk using data from the Pooling Project of Prospective Studies of Diet and Cancer. Methods: Associations with bladder cancer risk were assessed using individual-level data from 30 cohort studies from North America, Europe, Australia and Asia. Diet was assessed at enrolment using validated food frequency questionnaires or diet histories. Following a pre-specified analysis plan, study- and sex-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression, adjusted for smoking status and duration and other potential confounders, and pooled using inverse-variance-weighted random-effects meta-analysis. Results: During median follow-up across cohorts of 8–29 years, among 2,575,971 participants, 20,780 were diagnosed with bladder cancer. Processed meat intake was associated with increased bladder cancer risk (HR comparing ≥40 with <5 g/day = 1.08; 95% CI: 1.02–1.15; HR per 20 g/day = 1.02; 95% CI: 1.00–1.03). Weaker evidence of association with increased risk was also observed for unprocessed red meat (HR comparing ≥100 with <20 g/day = 1.06; 95% CI: 1.00–1.13; HR per 50 g/day = 1.01; 95% CI: 0.99–1.03). There was no evidence of heterogeneity by study, sex, or region. Conclusions: Higher intakes of processed meat and unprocessed red meat were associated with a small increase in risk of bladder cancer. These findings are consistent with existing public health recommendations to limit consumption of red and processed meat.

Background: Structural variations such as copy number variants (CNV) influence the expression of different phenotypic traits. Algorithms to identify CNVs through SNP-array platforms are available. The ability to evaluate well-characterized CNVs such as GSTM1 (1p13.3) deletion provides an important opportunity to assess their performance. Results: 773 cases and 759 controls from the SBC/EPICURO Study were genotyped in the GSTM1 region using TaqMan, Multiplex Ligation-dependent Probe Amplification (MLPA), and Illumina Infinium 1 M SNP-array platforms. CNV callings provided by TaqMan and MLPA were highly concordant and replicated the association between GSTM1 and bladder cancer. This was not the case when CNVs were called using Illumina 1 M data through available algorithms since no deletion was detected across the study samples. In contrast, when the Log R Ratio (LRR) was used as a continuous measure for the 5 probes contained in this locus, we were able to detect their association with bladder cancer using simple regression models or more sophisticated methods such as the ones implemented in the CNVtools package. Conclusions: This study highlights an important limitation in the CNV calling from SNP-array data in regions of common aberrations and suggests that there may be added advantage for using LRR as a continuous measure in association tests rather than relying on calling algorithms.

Disinfection by-products in drinking water are chemical contaminants that have been associated with cancer and other adverse effects. Exposure occurs from consumption of tap water, inhalation and dermal absorption. We determined the relationship between socioeconomic status and exposure to disinfection by-products in 1271 controls from a multicentric bladder cancer case-control study in Spain. Information on lifetime drinking water sources, swimming pool attendance, showering-bathing practices, and socioeconomic status (education, income) was collected through personal interviews. The most highly educated subjects consumed less tap water (57%) and more bottled water (33%) than illiterate subjects (69% and 17% respectively, p-value = 0.003). These differences became wider in recent time periods. The time spent bathing or showering was positively correlated with attained educational level (p < 0.001). Swimming pool attendance was more frequent among highly educated subjects compared to the illiterate (odds ratio = 3.4; 95% confidence interval 1.6-7.3). The most highly educated subjects were less exposed to chlorination by-products through ingestion but more exposed through dermal contact and inhalation in pools and showers/baths. Health risk perceptions and economic capacity may affect patterns of water consumption that can result in differences in exposure to water contaminants.

The etiology of pancreatic cancer is poorly understood, partly because of the inconsistency of findings among case-control studies of pancreatic cancer. Because of the unfavorable prognosis for pancreatic cancer, many case-control studies have been based largely on interviews with next of kin, who are known to report less reliable information on potential risk factors than original respondents. The purpose of this study was to estimate the effects of speculative risk factors such as dietary/nutritional factors and alcohol drinking, as well as those of established risk factors such as cigarette smoking, diabetes mellitus, and family history of pancreatic cancer, on pancreatic cancer risk based solely on direct interviews. This investigation was a population-based case-control study of pancreatic cancer diagnosed in Atlanta (GA), Detroit (MI), and ten New Jersey counties from August 1986 through April 1989. Direct interviews were conducted with 526 incident cases and 2,153 population controls. This study revealed a significant interaction between body mass index and caloric intake that was consistent by both race and gender. Subjects with elevated body mass index and caloric intake had increased risk, whereas those with elevated values for one of these factors but not the other experienced no increased risk. This finding suggests that energy balance may play a major role in pancreatic carcinogenesis. Diabetes mellitus was also a risk factor for pancreatic cancer, as well as a possible complication of the tumor. Our data are consistent with a key role for hyperinsulinemia in pancreatic carcinogenesis, particularly among non-diabetics with an elevated body mass index. A three-fold risk of pancreatic cancer among first-degree relatives of affected individuals was apparent. An increased risk also was associated with a family history of colon, endometrial, ovary, and breast cancer, suggesting a possible link to hereditary non-polyposis colon cancer. Our findings support a causal role for cigarette smoking in pancreatic carcinogenesis. Alcohol drinking at levels typically consumed by the general population of the United States did not appear to be a risk factor for pancreatic cancer, although heavy drinking may be related to risk, particularly in blacks. Teratogenesis Carcinog. Mutagen. 21:7–25, 2001. Published 2001 Wiley-Liss, Inc.