Bräuner et al. or Aarhus, and be cancer free at the time of invitation. A total of 57,053 persons of those invited were enrolled in the cohort. Upon enrollment, each participant completed self- administered questionnaires on dietary hab- its, health status, family history of cancer, social factors, reproductive factors, and life- style habits. Participation was based on written informed consent. Staff members in the study clinics obtained height and weight measure- ments and took a buttock adipose tissue biopsy from each participant, yielding an average of 29 mg (range, 1–97 mg) tissue. All samples were frozen at −20°C within 2 hr and put in liquid nitrogen vapor (maximum temperature, −150°C) for long-term storage within 8 hr of collection. The study was approved by regional ethics committees for Copenhagen and Aarhus. Using the unique personal identification number allocated to every Danish citizen, we linked all cohort members to the Danish Central Population Registry to obtain infor- mation on vital status, disappearance, and emigration. Follow-up for NHL started on the date of enrollment at one of the study clinics (baseline) and continued until date of diagnosis of any cancer (except nonmelanoma skin cancer), date of death, date of emigra- tion, or 31 July 2008 (end of follow-up), whichever came first. The mean and maxi- mum follow-up times were 9.6 and 15 years, respectively. Cancers diagnosed during follow-up were identified by linkage to the nationwide Danish Cancer Registry using the personal identification number. We excluded 9 of the identified NHL cases because of the diagnosis of another previ- ous cancer, resulting in 278 cases (152 men, 126 women) with NHL. Stored adipose tissue was missing for 22 cases, which were therefore excluded. We used a case–cohort design within the Diet, Cancer and Health cohort. A sub- cohort consisting of 256 persons was randomly selected among the entire cohort, regardless of case status. Of the final 512 participants, we excluded 17 cases and 11 subcohort per- sons because of either insufficient availability of adipose tissue for organochlorine analysis or laboratory analysis errors, leaving 239 cases (126 men, 113 women) and 245 subcohort persons (126 men, 119 women). Organochlorine analyses. The organo- chlorines measured were 10 PCB con- geners (congeners 99, 118, 138, 153, 156, 170, 180, 183, 187, and 201) and 8 pesti- cides analytes [p,p´-DDT, p,p´-dichloro- diphenyldichloroethylene (p,p´-DDE), β-hexachlorocyclohexane, dieldrin, hexachloro- benzene, cis-nonachlor, trans-nonachlor, and oxychlordane]. Samples were analyzed at the Centre de toxicologie du Québec, Institut National de Santé Publique du Québec Quebec City, Quebec, Canada. Laboratory personnel 106 were blind to the case status. The labora- tory is accredited under ISO 17025 by the Canadian Standards Council and participates in many quality control programs, including the Northern Contaminants Program of the Ministry of the Environment of Ontario, the U.K. National External Quality Assessment Scheme, and the German External Quality Assessment Scheme. The sample was aspirated from the needle into a vacuum-based collection vial. The tis- sue samples were then fortified with internal standards, mixed with dichloromethane, and chemically dried using sodium sulfate. Part of the organic solvent was used to determine the percentage of total lipids in the sample. The remaining fraction was concentrated by evaporation, and purified using gel per- meation chromatography, and cleaned up on a Florisil column (Agilent Technologies, Mississauga, Ontario, Canada). The extracts were analyzed on a gas chromatography/mass spectroscopy instrument (model 6890/5973; Agilent Technologies) using a DB-XLB cap- illary column [60 m long, 0.25 mm inner diameter and 0.25 mμ film thickness (Agilent Technologies)]. The measurement of ions generated after negative chemical ionization was performed in selective ion mode. The concentration calculations took the recov- ery of isotopically labeled internal standards into account. For additional information on instrumentation and analytical protocols, see Supplemental Material, page S2 (http:// dx.doi.org/10.1289/ehp.1103573). We determined the total lipid content of the designated extract using a gravimet- ric method. A 200 μL sample was precisely weighed on an analytic balance, and the sol- vent was evaporated at room temperature. The resulting lipid weight was adjusted to the ini- tial sample weight, and the percentage of lipid content was calculated. The organochlorine concentrations were expressed in microgram per kilogram of lipids. For each of the analytes, the limit of detec- tion (LOD) was determined by first estimating the concentration equivalent to a signal:noise ratio of 3. We then measured 10 replicates of a sample with the analyte at concentrations 4–10 times the estimated LOD and defined the final LOD as three times the standard deviation of the 10 replicates. The organochlorines could be divided into four groups according to LOD. Group 1 was PCB-99; group 2, p,p´-DDE, p,p´-DDT, and β-hexachlorocyclohexane; group 3, hexachlorobenzene; and group 4, all other compounds. The LOD was 1.00, 0.30, 0.20, and 0.10 gμ/kg for groups 1, 2, 3 , and 4, respectively. For each study sample, the LOD was adjusted according to the weight and lipid content of the sample, resulting in a wide range of sample-specific LODs for each compound. Routine checks of the accuracy and pre- cision of the organochlorine measurements were done using reference materials from the National Institute of Standards and Technology (Gaithersburg, MD, USA) and by participating in quality assessment schemes. The interday precision was 5.1–7.3% for the PCB congeners and 5.0–10.5% for the pes- ticides. Based on spiked levels (5 μg/kg in corn oil, n = 3), recovery was 87–96% for the different PCB congeners and 70–94% for the organochlorine pesticides. For details con- cerning analytical quality assurance/control and individual recoveries, see Supplemental Material, page S2 and Table S1 (http://dx.doi. org/10.1289/ehp.1103573). Statistical methods. In accordance with the sampling design, the incidence rate ratios (IRRs) for NHL were estimated by a Cox pro- portional hazard model (PHREG in SAS, ver- sion 9.1; SAS Institute Inc., Cary, NC, USA). The two-sided 95% confidence interval (CI) and p-values were based on the robust estimates of the variance-covariance matrix (Barlow 1994) and the Wald’s test statistic for regression parameters in Cox regression mod- els. All statistical tests were two sided, and statistical significance was defined as p < 0.05. Age was the time scale, ensuring the risk esti- mate was based on comparisons of individ- uals at the same age, thus adjusting for age (Thiebaut and Benichou 2004), and analyses were stratified according to sex. Based on the exposure distribution among all participants with levels above the LOD, we generated five exposure groups (0th– 25th, 25th–50th, 50th–75th, 75th–90th, and > 90th percentiles) for each compound. Cutoff percentiles were based on exposure distribution among all participants because we hypothesized that exposure increased the risk for NHL. Thus, basing cutoff percentiles on the exposure of the subcohort alone may have resulted in relatively few cases in the lowest exposure category (reference group), possibly compromising statistical power when estimat- ing IRRs for the upper exposure groups. Relative risk was estimated by contrasting each of the upper exposure groups with the lowest exposure group. Case and subcohort members with organochlorine levels below the LOD were excluded instead of being assigned a value based on the LOD, as the LOD varied substantially among study samples because of differences in lipid content. We investigated the sensitivity of the results relating to this exclusion by repeating categorical analyses with persons who had organochlorine levels below their sample-specific LOD assigned as follows: If the LOD for their adipose sample was below the 25th percentile of the distribution of meas- ured concentrations (based on all samples with values > LOD), the subject was assigned to the lowest exposure category. If the LOD for their ovlume 120 | number 1 | January 2012 • Environmental Health Perspectives