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Epidemiology and Genomics Research Program

Netherlands Cohort Study (NLCS)

Lead Contact and/or Principal Investigator (PI):

Funded Since: 1986
Funding Sources: Dutch Cancer Society, World Cancer Research Fund, the European Union (EU), the Netherlands Organisation for Health Research and Development (ZonMW)
Year(s) of Enrollment: 1986

The Netherlands Cohort Study (NLCS) started in 1986 and includes 120,852 men and women. The study population originates from 204 municipal population registries throughout The Netherlands, by gender-stratified random sampling.

At baseline in September 1986, a total of 120,852 participants (58,279 men and 62,573 women) between the ages of 55 and 69 years completed a mailed, self-administered questionnaire on dietary habits and other risk factors for cancer (e.g., anthropometry, physical activity history, smoking history, education, occupational history, reproductive history, history of drug use, radiation and radiotherapy, surgery, other medical history, and family history of cancer). Dietary intake was assessed using a 150-item semi-quantitative food frequency questionnaire (FFQ) that concentrated on habitual consumption of food and beverages. About 90,000 participants (75%) also provided toenail clippings at baseline. The toenail clippings were initially collected for determination of trace elements (selenium), and are now used as source of genomic DNA.

For efficiency reasons, a nested case-cohort approach is used for data processing and analysis: the cancer cases are enumerated for the entire cohort using record linkage (with the Netherlands Cancer Registry and the Dutch National Pathology Registry (PALGA), while the person years at risk accumulating in the cohort are estimated from a random sample (the so-called subcohort). The subcohort of 5,000 individuals (2,411 men and 2,589 women) was randomly sampled from the entire cohort immediately after baseline measurement and has been actively followed up regularly for vital status and migration information. Until 20.3 years of follow-up, only one male subcohort member was lost to follow-up, and the person time at risk of this person is censored at the time when he became lost to follow-up.

Exposure data from the questionnaires are key entered and processed for all incident cases in the cohort and for all subcohort members in a manner blinded with respect to case/subcohort status. An extensive database has been developed for the NLCS containing exposure and follow-up information. Survival analyses (Cox proportional hazards models) taking account of the case-cohort design are generally used to analyze relationships between exposures and risk of various cancers.

More than 230 papers have been published using the NLCS. Because tumor blocks also were collected, our molecular epidemiological projects focus on tumor heterogeneity (mol. defined), epigenetics, and genetic susceptibility.