Colon and rectal cancer incidence and water trihalomethane concentrations in New South Wales, Australia.
ABSTRACT: BACKGROUND: There is evidence, although inconsistent, that long term exposure to disinfection by products (DBPs) increases the risk of bowel cancer. No study has been conducted in Australia to examine this association and due to difference in the methods of disinfection the risk can vary across geographical regions and. This study was conducted to analyse the association of trihalomethanes (THMs) in water with colon and rectal cancer in NSW Australia. METHODS: Average yearly concentrations of total and individual species of THMs were obtained for 50 local government areas (LGAs). Indirectly-standardized incidence rates of colon and rectal cancers in LGAs for the period 1995 to 2001 were regressed against mean THM concentrations lagged five years, adjusting for socioeconomic status, high risk drinking, smoking status, usual source of water and year of diagnosis, including local and global random effects within a Bayesian framework. The incidence rate ratios (IRRs) for an interquartile range (IQR) increase in THMs were estimated. RESULTS: Using five year lag of exposure there was a positive association between bromoform concentration and CRC in men (IRR = 1.025, 95% CI 1.010, 1.040) but not in women (IRR = 1.003, 95% CI 0.987, 1.018). The association in men was mainly found in colon cancer with bromoform (IRR = 1.035, 95% CI 1.017, 1.053). There was no appreciable association of colorectal cancer with other species of THMs. Sensitivity analyses did not materially change the associations observed. CONCLUSION: A positive association was observed between colon cancer and water bromoform concentrations in men. Given the potential population impact of such an association, further research into the relationship between THMs, particularly brominated species, and colorectal cancer is warranted.
Project description:Exposure to trihalomethanes (or THMs: chloroform, bromoform, bromodichloromethane, and dibromochloromethane [DBCM]) formed via drinking water disinfection has been associated with adverse reproductive outcomes and cancers of the digestive or genitourinary organs. However, few studies have examined potential associations between THMs and liver injury in humans, even though experimental studies suggest that these agents exert hepatotoxic effects, particularly among obese individuals. This study examined participants in the National Health and Nutrition Examination Survey (1999-2006, N=2781) to test the hypothesis that THMs are associated with liver injury as assessed by alanine aminotransferase (ALT) activity in circulation. Effect modification by body mass index (BMI) or alcohol consumption also was examined. Associations between blood THM concentrations and ALT activity were assessed using unconditional multiple logistic regression to calculate prevalence odds ratios (ORs) with 95% confidence intervals (CIs) for exposure among cases with elevated ALT activity (men: >40IU/L, women: >30IU/L) relative to those with normal ALT, after adjustment for variables that may confound the relationship between ALT and THMs. Compared to controls, cases were 1.35 times more likely (95% CI: 1.02, 1.79) to have circulating DBCM concentrations exceeding median values in the study population. There was little evidence for effect modification by BMI, although the association varied by alcohol consumption. Among non-drinkers, cases were more likely than controls to be exposed to DBCM (OR: 3.30, 95% CI: 1.37, 7.90), bromoform (OR: 2.88, 95% CI: 1.21, 6.81), or brominated THMs (OR: 4.00, 95% CI: 1.31, 12.1), but no association was observed among participants with low, or moderate to heavy alcohol consumption. Total THM levels exceeding benchmark exposure limits continue to be reported both in the United States and globally. Results from this study suggest a need for further characterization of ALT activity and possibly other hepatic or metabolic diseases in populations with elevated drinking water THM concentrations.
Project description:Trihalomethanes (THMs) are water disinfection by-products that have been associated with bladder cancer and adverse birth outcomes. Four THMs (bromoform, chloroform, bromodichloromethane, dibromochloromethane) were measured in blood and tap water of U.S. adults in the National Health and Nutrition Examination Survey (NHANES) 1999-2006. THMs are metabolized to potentially toxic/mutagenic intermediates by cytochrome p450 (CYP) 2D6 and CYP2E1 enzymes.We conducted exploratory analyses of blood THMs, including factors affecting CYP2D6 and CYP2E1 activity.We used weighted multivariable regressions to evaluate associations between blood THMs and water concentrations, survey year, and other factors potentially affecting THM exposure or metabolism (e.g., prescription medications, cruciferous vegetables, diabetes, fasting, pregnancy, swimming).From 1999 to 2006, geometric mean blood and water THM levels dropped in parallel, with decreases of 32%-76% in blood and 38%-52% in water, likely resulting, in part, from the lowering of the total THM drinking water standard in 2002-2004. The strongest predictors of blood THM levels were survey year and water concentration (n = 4,232 total THM; n = 4,080 bromoform; n = 4,582 chloroform; n = 4,374 bromodichloromethane; n = 4,464 dibromochloromethane). We detected statistically significant inverse associations with diabetes and eating cruciferous vegetables in all but the bromoform model. Medications did not consistently predict blood levels. Afternoon/evening blood samples had lower THM concentrations than morning samples. In a subsample (n = 230), air chloroform better predicted blood chloroform than water chloroform, suggesting showering/bathing was a more important source than drinking.We identified several factors associated with blood THMs that may affect their metabolism. The potential health implications require further study.
Project description:BACKGROUND: Exposure to disinfection by-products (DBPs) in drinking water has been associated with cancer risk. A recent study (Villanueva et al. 2007; Am J Epidemiol 165:148-156) found an increased bladder cancer risk among subjects attending swimming pools relative to those not attending. OBJECTIVES: We evaluated adults who swam in chlorinated pools to determine whether exposure to DBPs in pool water is associated with biomarkers of genotoxicity. METHODS: We collected blood, urine, and exhaled air samples from 49 nonsmoking adult volunteers before and after they swam for 40 min in an indoor chlorinated pool. We estimated associations between the concentrations of four trihalomethanes (THMs) in exhaled breath and changes in micronuclei (MN) and DNA damage (comet assay) in peripheral blood lymphocytes before and 1 hr after swimming; urine mutagenicity (Ames assay) before and 2 hr after swimming; and MN in exfoliated urothelial cells before and 2 weeks after swimming. We also estimated associations and interactions with polymorphisms in genes related to DNA repair or to DBP metabolism. RESULTS: After swimming, the total concentration of the four THMs in exhaled breath was seven times higher than before swimming. The change in the frequency of micronucleated lymphocytes after swimming increased in association with higher exhaled concentrations of the brominated THMs (p = 0.03 for bromodichloromethane, p = 0.05 for chlorodibromomethane, p = 0.01 for bromoform) but not chloroform. Swimming was not associated with DNA damage detectable by the comet assay. Urine mutagenicity increased significantly after swimming, in association with the higher concentration of exhaled bromoform (p = 0.004). We found no significant associations with changes in micronucleated urothelial cells. CONCLUSIONS: Our findings support potential genotoxic effects of exposure to DBPs from swimming pools. The positive health effects gained by swimming could be increased by reducing the potential health risks of pool water.
Project description:Although incidence of colorectal cancer (CRC) in the United States has declined in recent years, rates remain higher in men than in women and the male-to-female incidence rate ratio (MF IRR) increases progressively across the colon from the cecum to the rectum. Rates among races/ethnicities other than Whites or Blacks have not been frequently reported. To examine CRC rates by sex across anatomic subsite, age and racial/ethnic groups, we used the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program for cases diagnosed among residents of 13 registries during 1992-2006. Incidence rates were expressed per 100,000 person-years and age-adjusted to the 2000 US Standard Population; MF IRR and 95% confidence intervals were also calculated. Among each racial/ethnic group, the MF IRR increased fairly monotonically from close to unity for cecal cancers to 1.81 (Hispanics) for rectal cancers. MF IRRs increased with age most rapidly for distal colon cancers from <1.0 at ages <50 years to 1.4-1.9 at older ages. The MF IRR for rectal cancers also rose with age from about 1.0 to 2.0. For proximal cancer, the MF IRR was consistently <1.5; among American Indian/Alaska Natives, it was <1.0 across all ages. The MF IRRs for CRC vary markedly according to subsite and age but less by racial/ethnic group. These findings may partially reflect differences in screening experiences and access to medical care but also suggest that etiologic factors may be playing a role.
Project description:Ingestion of disinfection byproducts has been associated with bladder cancer in multiple studies. Although associations with other routes of exposure have been suggested, epidemiologic evidence is limited.We evaluated the relationship between bladder cancer and total, chlorinated, and brominated trihalomethanes (THMs) through various exposure routes.In a population-based case–control study in New England (n=(1,213) cases; n=(1,418) controls), we estimated lifetime exposure to THMs from ingestion, showering/bathing, and hours of swimming pool use. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression adjusted for confounders.Adjusted ORs for bladder cancer comparing participants with exposure above the 95th percentile with those in the lowest quartile of exposure (based on the distribution in controls) were statistically significant for average daily intake mg/d of total THMs [OR=1.53 (95% CI: 1.01, 2.32), p-trend=0.16] and brominated THMs [OR=1.98 (95% CI: 1.19, 3.29), p-trend=0.03]. For cumulative intake mg, the OR at the 95th percentile of total THMs was 1.45 (95% CI: 0.95, 2.2), p-trend=0.13; the ORs at the 95th percentile for chlorinated and brominated THMs were 1.77 (95% CI: 1.05, 2,.99), p-trend=0.07 and 1.78 (95% CI: 1.05, 3.00), p-trend=0.02, respectively. The OR in the highest category of showering/bathing for brominated THMs was 1.43 (95% CI: 0.80, 2.42), p-trend=0.10. We found no evidence of an association for bladder cancer and hours of swimming pool use.We observed a modest association between ingestion of water with higher THMs (>95th?percentile?vs.<25th?percentile) and bladder cancer. Brominated THMs have been a particular concern based on toxicologic evidence, and our suggestive findings for multiple metrics require further study in a population with higher levels of these exposures. Data from this population do not support an association between swimming pool use and bladder cancer. https://doi.org/10.1289/EHP89.
Project description:We investigated the association of colorectal cancer risk factors with different colorectal cancer subsites to assess etiological differences for cancers of the proximal colon, distal colon, and rectum. Included in this study were 869,725 men and 395,501 women who participated in a health examination provided by the Korean National Health System between 1996 and 1997. During up to 7 years of follow-up, 4,144 incident colorectal cancer cases were detected (3,051 men and 1,093 women). Greater height was associated with elevated risk for distal colon cancer and rectal cancer in both men and women. Family history of cancer was associated with higher risk for cancers of the proximal colon in men and distal colon in both men and women. Frequent alcohol consumption and consuming high amounts of alcohol were associated with elevated risk for distal colon cancer in men and higher risk for rectal cancer in women. Frequent meat consumption was associated with risk for proximal colon cancer in men and for rectal cancer in women. Our findings suggest that risk factors for colorectal cancer are different by subsites of colon and rectum, as well as by sex.
Project description:Evidence on the association between colorectal cancer and exposure to disinfection by-products in drinking water is inconsistent.We assessed long-term exposure to trihalomethanes (THMs), the most prevalent group of chlorination by-products, to evaluate the association with colorectal cancer.A multicenter case-control study was conducted in Spain and Italy in 2008-2013. Hospital-based incident cases and population-based (Spain) and hospital-based (Italy) controls were interviewed to ascertain residential histories, type of water consumed in each residence, frequency and duration of showering/bathing, and major recognized risk factors for colorectal cancer. We estimated adjusted odds ratios (OR) for colorectal cancer in association with quartiles of estimated average lifetime THM concentrations in each participant's residential tap water (micrograms/liter; from age 18 to 2 years before the interview) and estimated average lifetime THM ingestion from drinking residential tap water (micrograms/day).We analyzed 2,047 cases and 3,718 controls. Median values (ranges) for average lifetime residential tap water concentrations of total THMs, chloroform, and brominated THMs were 30 (0-174), 17 (0-63), and 9 (0-145) ?g/L, respectively. Total THM concentration in residential tap water was not associated with colorectal cancer (OR = 0.92, 95% CI: 0.66, 1.28 for highest vs. lowest quartile), but chloroform concentrations were inversely associated (OR = 0.31, 95% CI: 0.24, 0.41 for highest vs. lowest quartile). Brominated THM concentrations showed a positive association among men in the highest versus the lowest quartile (OR = 1.43, 95% CI: 0.83, 2.46). Patterns of association were similar for estimated average THM ingestion through residential water consumption.We did not find clear evidence of an association between detailed estimates of lifetime total THM exposure and colorectal cancer in our large case-control study population. Negative associations with chloroform concentrations and ingestion suggest differences among specific THMs, but these findings should be confirmed in other study populations. Citation: Villanueva CM, Gracia-Lavedan E, Bosetti C, Righi E, Molina AJ, Martín V, Boldo E, Aragonés N, Perez-Gomez B, Pollan M, Gomez Acebo I, Altzibar JM, Jiménez Zabala A, Ardanaz E, Peiró R, Tardón A, Chirlaque MD, Tavani A, Polesel J, Serraino D, Pisa F, Castaño-Vinyals G, Espinosa A, Espejo-Herrera N, Palau M, Moreno V, La Vecchia C, Aggazzotti G, Nieuwenhuijsen MJ, Kogevinas M. 2017. Colorectal cancer and long-term exposure to trihalomethanes in drinking water: a multicenter case---control study in Spain and Italy. Environ Health Perspect 125:56-65;?http://dx.doi.org/10.1289/EHP155.
Project description:Polyphenols may play a chemopreventive role in colorectal cancer (CRC); however, epidemiological evidence supporting a role for intake of individual polyphenol classes, other than flavonoids is insufficient. We evaluated the association between dietary intakes of total and individual classes and subclasses of polyphenols and CRC risk and its main subsites, colon and rectum, within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The cohort included 476,160 men and women from 10 European countries. During a mean follow-up of 14 years, there were 5991 incident CRC cases, of which 3897 were in the colon and 2094 were in the rectum. Polyphenol intake was estimated using validated centre/country specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, a doubling in total dietary polyphenol intake was not associated with CRC risk in women (HRlog2?=?1.06, 95% CI 0.99-1.14) or in men (HRlog2?=?0.97, 95% CI 0.90-1.05), respectively. Phenolic acid intake, highly correlated with coffee consumption, was inversely associated with colon cancer in men (HRlog2?=?0.91, 95% CI 0.85-0.97) and positively associated with rectal cancer in women (HRlog2?=?1.10, 95% CI 1.02-1.19); although associations did not exceed the Bonferroni threshold for significance. Intake of other polyphenol classes was not related to colorectal, colon or rectal cancer risks. Our study suggests a possible inverse association between phenolic acid intake and colon cancer risk in men and positive with rectal cancer risk in women.
Project description:<h4>Background</h4>Colorectal cancer (CRC) incidence in the United States is declining rapidly overall but, curiously, is increasing among young adults. Age-specific and birth cohort patterns can provide etiologic clues, but have not been recently examined.<h4>Methods</h4>CRC incidence trends in Surveillance, Epidemiology, and End Results areas from 1974 to 2013 (n?=?490 305) were analyzed by five-year age group and birth cohort using incidence rate ratios (IRRs) and age-period-cohort modeling.<h4>Results</h4>After decreasing in the previous decade, colon cancer incidence rates increased by 1.0% to 2.4% annually since the mid-1980s in adults age 20 to 39 years and by 0.5% to 1.3% since the mid-1990s in adults age 40 to 54 years; rectal cancer incidence rates have been increasing longer and faster (eg, 3.2% annually from 1974-2013 in adults age 20-29 years). In adults age 55 years and older, incidence rates generally declined since the mid-1980s for colon cancer and since 1974 for rectal cancer. From 1989-1990 to 2012-2013, rectal cancer incidence rates in adults age 50 to 54 years went from half those in adults age 55 to 59 to equivalent (24.7 vs 24.5 per 100 000 persons: IRR?=?1.01, 95% confidence interval [CI]?=?0.92 to 1.10), and the proportion of rectal cancer diagnosed in adults younger than age 55 years doubled from 14.6% (95% CI?=?14.0% to 15.2%) to 29.2% (95% CI?=?28.5% to 29.9%). Age-specific relative risk by birth cohort declined from circa 1890 until 1950, but continuously increased through 1990. Consequently, compared with adults born circa 1950, those born circa 1990 have double the risk of colon cancer (IRR?=?2.40, 95% CI?=?1.11 to 5.19) and quadruple the risk of rectal cancer (IRR?=?4.32, 95% CI?=?2.19 to 8.51).<h4>Conclusions</h4>Age-specific CRC risk has escalated back to the level of those born circa 1890 for contemporary birth cohorts, underscoring the need for increased awareness among clinicians and the general public, as well as etiologic research to elucidate causes for the trend. Further, as nearly one-third of rectal cancer patients are younger than age 55 years, screening initiation before age 50 years should be considered.
Project description:Colorectal cancer is the third most common cancer worldwide, and many risk factors for colorectal cancer have been established. However, it remains uncertain whether psychological stress contributes to the onset of colorectal cancer. Therefore, we conducted a large-scale prospective cohort study to confirm the association between perceived stress and colorectal cancer incidence. We identified 680 cases of colon cancer and 330 cases of rectal cancer during a maximum of 21-year follow-up of 61,563 Japanese men and women. Cox regression analysis adjusted for potential confounders revealed a significant association of perceived stress with rectal cancer incidence but not with colon cancer incidence. This finding is partly consistent with that from only one previous study that addressed an association between perceived stress and the risk of colorectal cancer. However, studies on this topic are sparse and warrant further exploration.