Metal levels in waste pickers in Brasilia, Brazil: hair and nail as exposure matrices.

The aim of this cross-sectional study was to compare workplace conditions and metal exposures in 431 waste pickers who worked nearby at the Estrutural Dump in Brasilia utilizing hair (n = 310) and nail (n = 355) as matrices of exposure. Waste pickers were grouped according to their workplace (open waste dump: G1 and sorting plants: G2). Hair and nail samples were collected and analyzed using ICP-MS. The work duration in the facilities was significantly different between the groups with averages of 16.46 (8.48) yrs and 9.26 (6.28) yrs for hair donors in G1 and G2, and 15.92 (7.72) yrs and 8.55 (5.77) yrs for toenail donors in G1 and G2, respectively. The arithmetic means (µg/g) of cadmium, copper, lead, and manganese in hair were significantly higher in G2 (0.076 ± 0.133; 19.61 ± 18.16; 2.27 ± .56 and 3.87 ± 5.59, respectively) compared to G1 (0.069 ± 0.235; 15.72 ± 15.18; 1.72 ± 4.04 and 3.65 ± 5.5, respectively). Concentrations of arsenic, barium, cadmium, copper, cobalt, lead, manganese, and molybdenum in nail were significantly higher in G2 (0.57 ± 0.39; 22.74 ± 42.06; 0.1 ± 0.08; 22.7 ± 51.60; 0.48 ± 0.45; 4.69 ± 9.43; 19.07 ± 20.75; 1.80 ± 1.76, respectively) compared to G1 (0.40 ± 0.28; 15.32 ± 22.31; 0.08 ± 0.11; 11.91 ± 16.25; 0.37 ± 0.37; 3.94 ± 15.04; 13.01 ± 19.08; 1.16 ± 1.80, respective. Our findings suggest that the studied population was exposed to toxic metals and indicates the need for chemical exposure prevention policies to monitor chemical risk exposures in waste pickers.

Domain-specific effects of prenatal fluoride exposure on child IQ at 4, 5, and 6-12 years in the ELEMENT cohort.

OBJECTIVE: Prenatal exposure to fluoride has been associated with adverse neurodevelopmental outcomes. However, the neuropsychological profile of fluoride's developmental neurotoxicity at low levels and the stability of this relationship across childhood has not been characterized. We investigated the longitudinal and domain specific effect of prenatal fluoride exposure on IQ among children ages 4, 5, and 6-12 years in the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort. METHODS: We measured the average of maternal urinary fluoride at each trimester of pregnancy adjusted for creatinine (MUFCRE). Children were administered the McCarthy Scales of Children's Abilities at ages 4 (N = 386) and 5 (N = 308), and the Wechsler Abbreviated Scale of Intelligence at age 6-12 (N = 278). We used generalized estimating equation (GEE) models to estimate the population averaged effect of MUFCRE concentration on longitudinal General Cognitive Index (GCI)/Full-Scale IQ (FSIQ), Verbal IQ (VIQ), and Performance IQ (PIQ) scores (N = 348). We tested for possible interactions between MUFCRE and child sex as well as for MUFCRE and time point on children's IQ. All models controlled for relevant available covariates. RESULTS: The mean/median MUFCRE concentration was 0.90/0.83 mg/L (SD = 0.39; IQR, 0.64-1.11 mg/L). A 0.5 mg/L increase in MUFCRE predicted an average 2.12-point decrease in GCI/FSIQ (95% CI: -3.49, -0.75) and 2.63-point decrease in PIQ (95% CI: -3.87, -1.40). MUFCRE was marginally associated with VIQ across time (B = -1.29, 95% CI: -2.60, 0.01). No interactions between MUFCRE and child sex or MUFCRE and time were observed. CONCLUSION: The negative association between prenatal fluoride exposure and longitudinal IQ was driven by decrements in non-verbal intelligence (i.e. PIQ), suggesting that visual-spatial and perceptual reasoning abilities may be more impacted by prenatal fluoride exposure as compared to verbal abilities.

A Benchmark Dose Analysis for Maternal Pregnancy Urine-Fluoride and IQ in Children.

As a guide to establishing a safe exposure level for fluoride exposure in pregnancy, we applied benchmark dose modeling to data from two prospective birth cohort studies. We included mother-child pairs from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort in Mexico and the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort in Canada. Maternal urinary fluoride concentrations (U-F, in mg/L, creatinine-adjusted) were measured in urine samples obtained during pregnancy. Children were assessed for intelligence quotient (IQ) at age 4 (n = 211) and between six and 12 years (n = 287) in the ELEMENT cohort, and three to four years (n = 407) in the MIREC cohort. We calculated covariate-adjusted regression coefficients and their standard errors to assess the association of maternal U-F concentrations with children's IQ measures. Assuming a benchmark response of 1 IQ point, we derived benchmark concentrations (BMCs) and benchmark concentration levels (BMCLs). No deviation from linearity was detected in the dose-response relationships, but boys showed lower BMC values than girls. Using a linear slope for the joint cohort data, the BMC for maternal U-F associated with a 1-point decrease in IQ scores was 0.31 mg/L (BMCL, 0.19 mg/L) for the youngest boys and girls in the two cohorts, and 0.33 mg/L (BMCL, 0.20 mg/L) for the MIREC cohort and the older ELEMENT children. Thus, the joint data show a BMCL in terms of the adjusted U-F concentrations in the pregnant women of approximately 0.2 mg/L. These results can be used to guide decisions on preventing excess fluoride exposure in pregnant women.

A Canadian Population-Based Cohort to the Study Cost and Burden of Surgically Resected Hidradenitis Suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic debilitating disease with long-lasting comorbidities that impose direct and indirect costs on the health care system. However, limited studies have estimated the burden of this disease in Canada, and no population-based studies have previously addressed this condition. OBJECTIVES: This work describes the characteristics of a population-based HS cohort to address the existing knowledge gap on the burden of HS for the Canadian health care system. This cohort will provide a foundation for further studies about clinical outcomes and risk factors of HS by providing opportunities for merging additional databases. METHODS: Data on demographic information, morbidities, relative resource use, and the cost of sectorial services were obtained from the Institute for Clinical Evaluative Sciences (ICES). All residents of Ontario covered by the Ontario Health Insurance Plan (OHIP) between April 1, 2002, and March 31, 2013, who underwent surgery for HS, defined by OHIP billing codes, were included. RESULTS: A total of 6244 cases were included in the analysis, following quality control procedures. Twice as many females were treated surgically relative to males. The majority of individuals treated were under the age of 64, with more than half having a moderate level of morbidity (according to Resource Utilization Bands defined by the Johns Hopkins Adjusted Clinical Group Classification System). CONCLUSIONS: This cohort study is the first population-based resource about HS in Canada. Administrative population-based databases provide essential information to assess the burden of chronic diseases and identify factors associated with higher cost.

Physical activity, obesity and survival in diffuse large B-cell and follicular lymphoma cases.

There is limited information concerning the impact of physical activity and obesity on non-Hodgkin lymphoma (NHL) prognosis. We examined the associations between pre-diagnosis physical activity and body mass index (BMI) with survival in 238 diffuse large B-cell (DLBCL) and 175 follicular lymphoma cases, with follow-up from 2000 to 2015. The most physically active DLBCL cases had 41% lower risk of dying in the follow-up period than the least active [Hazard ratio (HR) = 0·59, 95% confidence interval (CI) = 0·36-0·96], while obese follicular lymphoma cases had a 2·5-fold risk of dying (HR = 2·52, 95% CI = 1·27-5·00) compared with cases with normal BMI. NHL-specific survival results were similar.

Urinary and plasma fluoride levels in pregnant women from Mexico City.

BACKGROUND: There is need to assess the developmental neurotoxicity of fluoride. Our knowledge of prenatal fluoride exposure is challenged as few population-based studies have been conducted and these generally date back several decades, provide incomplete data on sociodemographic variables, and have methodological limitations. OBJECTIVE: To measure urinary and plasma fluoride levels across three time points in pregnant mothers who were enrolled in the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) birth cohort study. METHODS: Fluoride levels were characterized in archived urine and plasma from 872 pregnant mothers sampled from the ELEMENT cohort. Various statistical methods were used to analyze the fluoride data with particular consideration for changes across three stages of pregnancy and against sociodemographic variables. RESULTS: All samples had detectable levels of fluoride. The mean urinary and plasma fluoride levels were 0.91 and 0.0221mg/L respectively, and these were not statistically different across three stages of pregnancy. Fluoride levels correlated across the stages of pregnancy studied, with stronger correlations between neighboring stages. Urinary fluoride changed as pregnancy progressed with levels increasing until ~23 weeks and then decreasing until the end of pregnancy. For plasma fluoride, there was a decreasing trend but this was not of statistical significance. Creatinine-adjusted urinary fluoride levels did not associate consistently with any of the sociodemographic variables studied. CONCLUSIONS: This study provides the most extensive characterization to date of fluoride exposure throughout pregnancy. These results provide the foundation to explore exposure-related health outcomes in the ELEMENT cohort and other studies.

Recurrence of hidradenitis suppurativa after surgical management: A systematic review and meta-analysis.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease of apocrine-bearing skin. Treatment is challenging and long-standing. Surgery is one of the treatment options with varying reported success rates. OBJECTIVE: This study provides a comprehensive systematic review of surgical approaches in the management of HS. METHODS: A systematic literature search and meta-analysis of proportions were performed on the included studies. RESULTS: Of a total of 1147 retrieved articles, 22 were included in the analysis. These were the estimated average recurrences: wide excision, 13.0% (95% confidence interval [CI], 5.0-22.0%); local incision, 22.0% (95% CI, 10.0-37.0%); and deroofing, 27.0% (95% CI, 23.0-31.0%). In the wide excision group, recurrence rates were as follows: 15% (95% CI, 0-72%) for primary closure, 8% (95% CI, 2.0-16.0%) for using flaps, and 6.0% (95% CI, 0.0-24.0%) for grafting. The secondary intention healing option was most commonly chosen after local excision and deroofing. LIMITATIONS: There was poor quality evidence and potential improper reporting of the results. CONCLUSION: This systematic review found lower recurrence rates with wide excision, using skin flaps or skin grafts as the closure methods. The heterogeneity of the patient populations was high and statistically significant within and across all types of excisions.

Hidradenitis Suppurativa: A Frequently Missed Diagnosis, Part 2: Treatment Options.

Hidradenitis suppurativa (HS) is a chronic inflammatory disorder of the intertriginous area. Patients with HS have several challenges to their quality of life and activities of everyday living, including malodor, purulent discharge, and discomfort. There is often a delay in diagnosis and appropriate treatment. The need for cosmetically acceptable local treatments and dressing application makes this disease an important challenge for wound care specialists. The choice of optimal treatment varies depending on the disease severity, expert knowledge, the availability of an interprofessional team, and patient factors.

Hidradenitis Suppurativa: A Frequently Missed Diagnosis, Part 1: A Review of Pathogenesis, Associations, and Clinical Features.

PURPOSE: To provide information about the etiology, diagnostic evaluations, and clinical features of hidradenitis suppurativa (HS). TARGET AUDIENCE: This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. OBJECTIVES: After participating in this educational activity, the participant should be better able to:1. Identify the prevalence, pathophysiology, and risk factors associated with HS.2. Describe diagnostic evaluations, staging, and comorbid disorders associated with HS. Hidradenitis Suppurativa (HS) is a recurrent inflammatory follicular disease that commonly affects the apocrine-bearing skin. The aim of this continuing education article is to review the pathogenesis and clinical presentations of HS. The spectrum of clinical presentations ranges from subcutaneous nodules to draining sinus and fistula. The pathogenesis of HS remains unknown.

The prognostic effect of ethnicity for gastric and esophageal cancer: the population-based experience in British Columbia, Canada.

BACKGROUND: Gastric and esophageal cancers are among the most lethal human malignancies. Their epidemiology is geographically diverse. This study compares the survival of gastric and esophageal cancer patients among several ethnic groups including Chinese, South Asians, Iranians and Others in British Columbia (BC), Canada. METHODS: Data were obtained from the population-based BC Cancer Registry for patients diagnosed with invasive esophageal and gastric cancer between 1984 and 2006. The ethnicity of patients was estimated according to their names and categorized as Chinese, South Asian, Iranian or Other. Cox proportional hazards regression analysis was used to estimate the effect of ethnicity adjusted for patient sex and age, disease histology, tumor location, disease stage and treatment. RESULTS: The survival of gastric cancer patients was significantly different among ethnic groups. Chinese patients showed better survival compared to others in univariate and multivariate analysis. The survival of esophageal cancer patients was significantly different among ethnic groups when the data was analyzed by a univariate test (p = 0.029), but not in the Cox multivariate model adjusted for other patient and prognostic factors. CONCLUSIONS: Ethnicity may represent underlying genetic factors. Such factors could influence host-tumor interactions by altering the tumor's etiology and therefore its chance of spreading. Alternatively, genetic factors may determine response to treatments. Finally, ethnicity may represent non-genetic factors that affect survival. Differences in survival by ethnicity support the importance of ethnicity as a prognostic factor, and may provide clues for the future identification of genetic or lifestyle factors that underlie these observations.

Prevalence of musculoskeletal disorders and risk factors in recyclable material waste pickers from the dump of the structural city in Brasília, Brazil.

Solid waste management is a global challenge impacting the lives of thousands of people, among them the recyclable materials waste pickers, through the separation and sale of these materials, make a living for themselves. These workers face unhealthy working conditions and are exposed to various occupational risks, which predispose the prevalence of musculoskeletal as chronic back problems. METHOD: Exploratory cross-sectional study with a semi-structured questionnaire to investigate the prevalence of back pain and related risk factors. RESULTS: 1.025 waste pickers were interviewed, and 970 records of chronic back pain were detected. Among them, 660 were women (68.04%), 310 were men (31.96%), the average age of 40.21 years; 597 were single (61.92%); 629 (64.84%) had over 11 years of work; 942 (97.11%) worked exclusively in the open dump, 899 (92.68%) with bags, 922 (95.05%) on dayshift. We found significant associations between gender (p < 0.001); age (p < 0.001); time at work (p < 0.022) and place at work (p < 0.001). After adjusting, there were higher prevalence of chronic back pain women (OR = 1.7), older age (OR = 2.64); working more than 11 years (OR = 1.09); and working on the open dump (OR = 2.8). CONCLUSION: The prevalence of subjective symptoms of musculoskeletal disorders was high. Women, over 36 years old, who worked more than 11 h a day in the open dump were more exposed to suffer from chronic back problems. The importance of urgently addressing the labor impacts related to solid waste management in developing countries to protect these workers and, especially, women involved in this work is emphasized.

A Benchmark Dose Analysis for Maternal Pregnancy Urine-Fluoride and IQ in Children.

As a safe exposure level for fluoride in pregnancy has not been established, we used data from two prospective studies for benchmark dose modeling. We included mother-child pairs from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort in Mexico and the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort in Canada. Children were assessed for IQ at age 4 (n=211) and between 6 and 12 years (n=287) in the ELEMENT cohort and between ages 3 and 4 years (n=512) in the MIREC cohort. We calculated covariate-adjusted regression coefficients and their standard errors to explore the concentration-effect function for maternal urinary fluoride with children's IQ, including possible sex-dependence. Assuming a benchmark response of 1 IQ point, we derived benchmark concentrations (BMCs) of maternal urinary fluoride and benchmark concentration levels (BMCLs). No deviation from linearity was detected from the results of the two studies. Using a linear slope, the BMC for maternal urinary fluoride associated with a 1-point decrease in IQ scores of preschool-aged boys and girls was 0.29 mg/L (BMCL, 0.18 mg/L). The BMC was 0.30 mg/L (BMCL, 0.19 mg/L) when pooling the IQ scores from the older ELEMENT children and the MIREC cohort. Boys showed slightly lower BMC values compared with girls. Relying on two prospective studies, maternal urine-fluoride exposure at levels commonly occurring in the general population, the joint data showed BMCL results about 0.2 mg/L. These results can be used to guide decisions on preventing excess fluoride exposure in vulnerable populations.

Comparison of breast cancer survival in two populations: Ardabil, Iran and British Columbia, Canada.

BACKGROUND: Patterns in survival can provide information about the burden and severity of cancer, help uncover gaps in systemic policy and program delivery, and support the planning of enhanced cancer control systems. The aim of this paper is to describe the one-year survival rates for breast cancer in two populations using population-based cancer registries: Ardabil, Iran, and British Columbia (BC), Canada. METHODS: All newly diagnosed cases of female breast cancer were identified in the Ardabil cancer registry from 2003 to 2005 and the BC cancer registry for 2003. The International Classification of Disease for Oncology (ICDO) was used for coding cancer morphology and topography. Survival time was determined from cancer diagnosis to death. Age-specific one-year survival rates, relative survival rates and weighted standard errors were calculated using life-tables for each country. RESULTS: Breast cancer patients in BC had greater one-year survival rates than patients in Ardabil overall and for each age group under 60. CONCLUSION: These findings support the need for breast cancer screening programs (including regular clinical breast examinations and mammography), public education and awareness regarding early detection of breast cancer, and education of health care providers.

Waterborne diseases in waste pickers of Estrutural, Brazil, the second largest open-air dumpsite in world.

Brazil was home to the second largest open-air dump in the world, Estrutural, which officially closed in January of 2018; however, many dumpsites throughout the country continue to operate informally. Prior to government-recognized closure, there were about 1200 waste pickers working at the dump. These workers were subject to a myriad of occupational and environmental risks; one primary hazard involved exposure to contaminated water, which significantly affects health and quality of life. As part of the official closure plan for Estrutural, a study was conducted to determine the occurrence of waterborne diseases and rates of intestinal worms among the workers. A convergent parallel mixed methods approach, using a cross-sectional study and semi-structured interviews, sought to uncover answers to these objectives. There were 1025 waste pickers used in this study. Data confirmed waste pickers experienced continuous bouts of waterborne disease cases through episodic diarrhea (24.9%), intestinal worms (12.6%), hepatitis A (1.7%) and leptospirosis (0.7%). People who lived in unregulated areas (favelas) had increased risk of diarrhea (OR = 1.72) and those who did not use filtered water were at increased risk of intestinal worms (OR = 1.87) and diarrhea (OR = 1.5). Qualitative and quantitative data confirmed that many workers suffered from waterborne diseases, and that women were at greater risk than men. These findings highlight unsanitary and poor occupational health conditions for waste pickers at dumpsites, which likely continue despite official dumpsite closures. Moreover, this data provide evidence of supplemental occupational hazards to assess at dumpsites worldwide, especially for women.

Prenatal fluoride exposure and attention deficit hyperactivity disorder (ADHD) symptoms in children at 6-12 years of age in Mexico City.

BACKGROUND: Epidemiologic and animal-based studies have raised concern over the potential impact of fluoride exposure on neurobehavioral development as manifested by lower IQ and deficits in attention. To date, no prospective epidemiologic studies have examined the effects of prenatal fluoride exposure on behavioral outcomes using fluoride biomarkers and sensitive measures of attention. OBJECTIVE: We aimed to examine the association between prenatal fluoride exposure and symptoms associated with attention-deficit/hyperactivity disorder (ADHD). METHOD: 213 Mexican mother-children pairs of the Early Life Exposures to Environmental Toxicants (ELEMENT) birth cohort study had available maternal urinary samples during pregnancy and child assessments of ADHD-like behaviors at age 6-12. We measured urinary fluoride levels adjusted for creatinine (MUFcr) in spot urine samples collected during pregnancy. The Conners' Rating Scales-Revised (CRS-R) was completed by mothers, and the Conners' Continuous Performance Test (CPT-II) was administered to the children. RESULTS: Mean MUFcr was 0.85 mg/L (SD = 0.33) and the Interquartile Range (IQR) was 0.46 mg/L. In multivariable adjusted models using gamma regression, a 0.5 mg/L higher MUFcr (approximately one IQR higher) corresponded with significantly higher scores on the CRS-R for DSM-IV Inattention (2.84 points, 95% CI: 0.84, 4.84) and DSM-IV ADHD Total Index (2.38 points, 95% CI: 0.42, 4.34), as well as the following symptom scales: Cognitive Problems and Inattention (2.54 points, 95% CI: 0.44, 4.63) and ADHD Index (2.47 points; 95% CI: 0.43, 4.50). The shape of the associations suggested a possible celling effect of the exposure. No significant associations were found with outcomes on the CPT-II or on symptom scales assessing hyperactivity. CONCLUSION: Higher levels of fluoride exposure during pregnancy were associated with global measures of ADHD and more symptoms of inattention as measured by the CRS-R in the offspring.

Prenatal Fluoride Exposure and Cognitive Outcomes in Children at 4 and 6-12 Years of Age in Mexico.

BACKGROUND: Some evidence suggests that fluoride may be neurotoxic to children. Few of the epidemiologic studies have been longitudinal, had individual measures of fluoride exposure, addressed the impact of prenatal exposures or involved more than 100 participants. OBJECTIVE: Our aim was to estimate the association of prenatal exposure to fluoride with offspring neurocognitive development. METHODS: We studied participants from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) project. An ion-selective electrode technique was used to measure fluoride in archived urine samples taken from mothers during pregnancy and from their children when 6-12 y old, adjusted for urinary creatinine and specific gravity, respectively. Child intelligence was measured by the General Cognitive Index (GCI) of the McCarthy Scales of Children's Abilities at age 4 and full scale intelligence quotient (IQ) from the Wechsler Abbreviated Scale of Intelligence (WASI) at age 6-12. RESULTS: We had complete data on 299 mother-child pairs, of whom 287 and 211 had data for the GCI and IQ analyses, respectively. Mean (SD) values for urinary fluoride in all of the mothers (n=299) and children with available urine samples (n=211) were 0.90 (0.35) mg/L and 0.82 (0.38) mg/L, respectively. In multivariate models we found that an increase in maternal urine fluoride of 0.5mg/L (approximately the IQR) predicted 3.15 (95% CI: -5.42, -0.87) and 2.50 (95% CI -4.12, -0.59) lower offspring GCI and IQ scores, respectively. CONCLUSIONS: In this study, higher prenatal fluoride exposure, in the general range of exposures reported for other general population samples of pregnant women and nonpregnant adults, was associated with lower scores on tests of cognitive function in the offspring at age 4 and 6-12 y. https://doi.org/10.1289/EHP655.

Clinical Features and Patient Outcomes of Hidradenitis Suppurativa: A Cross-Sectional Retrospective Study.

BACKGROUND: Despite the high burden of disease associated with hidradenitis suppurativa (HS), epidemiologic data are scarce. OBJECTIVE: The objective was to review demographic features and clinical findings in 80 HS patients from 2 referral centres in Ontario, Canada, from October 2013 to September 2014, and to assess for factors that are associated with more advanced disease. METHODS: Multicentre cross-sectional study. The data on demographic and clinical features were obtained by questionnaires and chart review. RESULTS: Of a total of 80 patients (67.5% females), percentages of patients in Hurley stages I, II, and III were 15.4%, 55.8%, and 28.9%, respectively. Most patients were not diagnosed for more than 1 year (70.1%). Patients with more severe disease were more likely to be females and to have a greater number of lesions and were less likely to be diagnosed initially by a dermatologist. CONCLUSIONS: This study documents the common demographic and clinical features of HS to optimize resource allocation and patient outcomes.

Genetic polymorphisms at TIMP3 are associated with survival of adenocarcinoma of the gastroesophageal junction.

The poor survival of adenocarcinomas of the gastroesophageal junction (GEJ) makes them clinically important. Discovery of host genetic factors that affect outcome may guide more individualized treatment. This study tests whether constitutional genetic variants in matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) genes are associated with outcome of GEJ adenocarcinoma. Single nucleotide polymorphisms (SNPs) at four TIMP (TIMP1-4) and three MMP genes (MMP2, MMP7 and MMP9) were genotyped in DNA samples from a prospective cohort of patients with primary adenocarcinoma of the GEJ admitted to the British Columbia Cancer Agency. Cox proportional hazards regression, with adjustment for patient, disease and treatment variables, was used to estimate the association of SNPs with survival. Genotypes for 85 samples and 48 SNPs were analyzed. Four SNPs across TIMP3, (rs130274, rs715572, rs1962223 and rs5754312) were associated with survival. Interaction analyses revealed that the survival associations with rs715572 and rs5754312 are specific and significant for 5FU+cisplatin treated patients. Sanger sequencing of the TIMP3 coding and promoter regions revealed an additional SNP, rs9862, also associated with survival. TIMP3 genetic variants are associated with survival and may be potentially useful in optimizing treatment strategies for individual patients.