This study shows case-by-case expert assessment to result in the lowest prevalence of occupational exposure in the NLCS. Furthermore, the DOMJEM and FINJEM proved to be rather similar in agreement when compared with the expert assessment. The Asbestos JEM appeared to be less appropriate for use in the NLCS.

Asbestos levels encountered at the lower end of the exposure distribution may be associated with an increased risk of pleural mesothelioma, lung cancer, and laryngeal cancer.

The evidence for an association between occupational asbestos exposure and esophageal, gastric and colorectal cancer is limited. We studied this association specifically addressing risk differences between relatively low and high exposure, risk associated with cancer subtypes, the influence of potential confounders and the interaction between asbestos and smoking in relation to cancer risk. Using the Netherlands Cohort Study (n 5 58,279 men, aged 55-69 years at baseline), asbestos exposure was estimated by linkage to a job-exposure matrix. After 17.3 years of follow-up, 187 esophageal, 486 gastric and 1,724 colorectal cancer cases were available for analysis. The models adjusted for age and family history of cancer showed that mainly (prolonged) exposure to high levels of asbestos was statistically significantly associated with risk of esophageal adenocarcinoma (EAC), total and distal colon cancer and rectal cancer. For overall gastric cancer and gastric non-cardia adenocarcinoma (GNCA), also exposure to lower levels of asbestos was associated. Additional adjustment for lifestyle confounders, especially smoking status, yielded non-significant associations with overall gastric cancer and GNCA in the multivariableadjusted model, except for the prolonged highly exposed subjects (tertile 3 vs. never: HR 2.67, 95% CI: 1.11-6.44 and HR 3.35, 95% CI: 1.33-8.44, respectively). No statistically significant additive or multiplicative interaction between asbestos and smoking was observed for any of the studied cancers. This prospective population-based study showed that (prolonged) high asbestos exposure was associated with overall gastric cancer, EAC, GNCA, total and distal colon cancer and rectal cancer.The International Agency for Research on Cancer evaluated the evidence for an association between asbestos exposure and gastric and colorectal cancer as limited, though for colorectal cancer they were evenly divided as to whether the evidence was strong enough to justify classification as sufficient. 1 For esophageal cancer, a relatively rare cancer, results of epidemiological studies on associations with asbestos are mixed and together with the fact that animal experiments do not support biological activity of asbestos at this site, the evidence was considered to be inadequate. 2 Therefore, the question remains whether asbestos entails an increased risk of developing gastrointestinal tumors, and if so, whether risk differs for relatively low and high exposure levels. As there are numerous other risk factors for gastrointestinal cancers, an additional question relates to the influence of potential confounders. Furthermore, cancer subtypes may have different etiologies and should be studied separately if possible. Finally, as for lung cancer, the question arises if interaction between asbestos and smoking is present in relation to gastrointestinal cancers. 1,2

The alcohol-colorectal cancer (CRC) association may differ by sex and ADH1B and ADH1C genotypes. ADH enzymes oxidize ethanol to acetaldehyde, both of which are human carcinogens. The Netherlands Cohort Study includes 120 852 participants, aged 55-69 years at baseline (1986), and has 20.3 years follow-up (case-cohort: nsubcohort = 4774; ncases = 4597). The baseline questionnaire included questions on alcohol intake at baseline and 5 years before. Using toenail DNA, available for ~75% of the cohort, we successfully genotyped six ADH1B and six ADH1C SNPs (nsubcohort = 3897; ncases = 3558). Sex- and subsite-specific Cox hazard ratios and 95% confidence intervals for CRC were estimated comparing alcohol categories, genotypes within drinkers and alcohol categories within genotype strata. We used a dominant genetic model and adjusted for multiple testing. Alcohol intake increased CRC risk in both sexes, though in women only in the (proximal) colon when in excess of 30 g/day. In male drinkers, ADH1B rs4147536 increased (distal) colon cancer risk. In female drinkers, ADH1C rs283415 increased proximal colon cancer risk. ADH1B rs3811802 and ADH1C rs4147542 decreased CRC risk in heavy (>30 g/day) and stable drinkers (compared to 5 years before baseline), respectively. Rs3811802 and rs4147542 significantly modified the alcohol-colon cancer association in women (Pfor interaction = 0.004 and 0.02, respectively). A difference in associations between genotype strata was generally clearer in men than women. In conclusion, men showed increased CRC risks across subsites and alcohol intake levels, while only colon cancer risk was increased in women at heavy intake levels. ADH1B rs3811802 and ADH1C rs4147542 significantly modified the alcohol-colon cancer association in women.

Results of this study indicate that using automated crosswalks to recode job codes from one occupational classification system to another results only in a limited loss in agreement in assigned occupational exposure estimates compared with direct manual recoding. Therefore, in this case, crosswalks provide an efficient alternative to the costly and time-consuming direct manual recoding from job history descriptions from questionnaires.

Occupational asbestos exposure and risk of oral cavity and pharyngeal cancer in the prospective Netherlands Cohort Study by Offermans NSM, Vermeulen R, Burdorf A, Goldbohm RA, Keszei AP, Peters S, Kauppinen T, Kromhout H, van den Brandt PA Within a population-based study, we estimate the association between occupational asbestos exposure and risk of oral cavity and pharyngeal cancer. There was no convincing evidence of an association between asbestos and risk of both cancers, as an exposure-response relation was lacking. However, the potentially increased hazard ratios of pharyngeal cancer observed in this and previous studies warrant further research. Original article Scand J Work Environ Health. 2014;40(4):420-427. doi:10.5271/sjweh.3434 Occupational asbestos exposure and risk of oral cavity and pharyngeal cancer in the prospective Netherlands Cohort Study Objectives The evidence for an association between occupational asbestos exposure and pharyngeal cancer (PhC) is limited, while for oral cavity cancer (OCC) the literature is even sparser. We studied OCC and PhC risk both separately and combined (OCPC) in relation to occupational asbestos exposure, specifically addressing the influence of potential confounders, the existence of an exposure-response relation, and the presence of interaction between asbestos and smoking. AffiliationMethods Using the prospective Netherlands Cohort Study (N=58 279 men, aged 55-69 years), we estimated asbestos exposure by linkage to a general population job-exposure matrix (DOMJEM) and a Finnish job-exposure matrix (FINJEM). After 17.3 years of follow-up, 58 OCC and 53 PhC cases were available for analysis. ResultsNo association between asbestos and risk of OCC was observed for either JEM. Hazard ratios (HR) of PhC and OCPC increased after adjusting for confounders, particularly alcohol consumption and socioeconomic status. For PhC, a multivariable-adjusted increased HR was observed for "ever" versus "never" exposed to asbestos [HR 2.20, 95% confidence interval (95% CI) 1.08-4.49] when using FINJEM, but a trend of increased risks with higher cumulative exposure could not be demonstrated for either JEM. Results for OCPC showed patterns similar to those observed for PhC. None of the cancers showed a significant interaction between asbestos and smoking.Conclusions This prospective population-based study showed no convincing evidence of an association between asbestos and risk of OCC, PhC, and OCPC as an exposure-response relation was lacking, and results were not robust against the use of different JEM. However, the potentially increased HR of PhC and OCPC observed in this and previous studies warrant further research.

Adult‐attained height is a marker for underlying mechanisms, such as cell growth, that may also influence postmenopausal breast cancer (BC) risk, perhaps specifically hormone‐sensitive BC subtypes. Early life energy restriction may inhibit these mechanisms, resulting in shorter height and a reduced postmenopausal BC risk. Women (62,573) from the Netherlands Cohort Study completed a self‐administered questionnaire in 1986 when 55–69 years old, and were followed‐up for 20.3 years (case–cohort: Nsubcohort = 2,438; Ncases = 3,354). Cox multivariable‐adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated for BC risk overall and by estrogen and progesterone receptor subtypes in relation to height and early life energy restriction during the Hunger Winter, War Years, and Economic Depression. Although energy restriction can only influence longitudinal growth in women exposed before and/or during the growth spurt, it may also influence BC risk when occurring after the growth spurt, possibly through different growth processes. Therefore, Cox analyses were additionally conducted according to timing of energy restriction in relation to the growth spurt. Height was associated with an increased BC risk (HRper 5cm = 1.07, 95%CI:1.01–1.13), particularly hormone receptor‐positive BC. Energy restriction before and/or during the growth spurt was associated with a decreased hormone receptor‐positive BC risk. Energy restriction during the Hunger Winter increased the estrogen receptor‐negative BC risk regardless of the timing of energy restriction. In conclusion, height and energy restriction before and/or during the growth spurt were both associated with hormone receptor‐positive BC risk, in the direction as expected, indicating critical exposure windows for hormonal growth‐related mechanisms.

Objectives Although asbestos research has been ongoing for decades, there are remaining questions regarding cancer risk associated with low exposure and cancer subtypes, the influence of potential confounders, and the interaction between asbestos and smoking. We addressed these questions by studying the association between occupational asbestos exposure and pleural mesothelioma, lung and laryngeal cancer in the prospective population-based Netherlands Cohort Study (NLCS). Methods The NLCS includes 58279 men aged 55–69 years at enrollment in 1986. Based on job history information obtained from a self-administered questionnaire, asbestos exposure was estimated by linkage to job-exposure matrices. After 17.3 years of follow-up, 132 cases of pleural mesothelioma, 2324 cases of lung cancer, and 166 cases of laryngeal cancer were available for analysis. Results Overall, occupational asbestos exposure was associated with an increased risk of mesothelioma, lung and laryngeal cancer, also for relatively low exposure. Correcting for potential confounders as age, smoking, alcohol, and several occupational carcinogens hardly influenced these results. Associations with lung cancer subtypes were generally comparable to overall lung cancer, except for adenocarcinoma (HR ever versus never exposed = 1.43, 1.52, 1.49 and 0.94 for small cell, large cell, squamous cell and adenocarcinoma respectively). Adenocarcinoma showed only a weak positive association at higher exposure levels for long duration. For laryngeal cancer, associations were usually stronger for supraglottis cancer (HR = 2.48, 95% CI:1.33–4.65) than glottis cancer (HR = 1.12, 95% CI:0.74–1.69). There was no statistically significant additive or multiplicative interaction between asbestos and smoking for any of the cancers. Conclusions The well-established associations between asbestos and mesothelioma, lung and laryngeal cancer were corroborated at relatively low levels of cumulative exposure in the NLCS. Lung adenocarcinoma may only show an increased relative risk at higher asbestos exposure for long duration. Asbestos exposure may be stronger associated with supraglottis cancer than glottis cancer.