Occupational solvent exposure and adult chronic lymphocytic leukemia: No risk in a population‐based case–control study in four Nordic countries

The aim of this study was to assess the effect of occupational solvent exposure on the risk of adult chronic lymphocytic leukemia (CLL). The current case–control study was nested in the Nordic Occupational Cancer Study (NOCCA) cohort. 20,615 CLL cases diagnosed in 1961–2005 in Finland, Iceland, Norway, and Sweden, and 103,075 population‐based controls matched by year of birth, sex, and country were included. Occupational histories for cases and controls were obtained from census records in 1960, 1970, 1980/1981, and 1990. Exposure to selected solvents was estimated by using the NOCCA job‐exposure matrix (NOCCA‐JEM). Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by using conditional logistic regression models. Overall, nonsignificant CLL risk elevations were observed for methylene chloride, perchloroethylene, and 1,1,1‐trichloroethane. Compared to unexposed, significantly increased risks were observed for cumulative perchloroethylene exposure ≤13.3 ppm‐years (OR = 1.85, 95% CI 1.16–2.96) and average life‐time perchloroethylene exposure ≤2.5 ppm (1.61, 95% CI 1.01–2.56) among women, and cumulative methylene chloride exposure ≤12.5 ppm‐years (OR = 1.19, 95% CI 1.01–1.41) and 12.5–74.8 ppm‐years (OR = 1.23, 95% CI 1.01–1.51) among men in an analysis with 5 years lag‐time, though without dose–response pattern. Decreased CLL risk was observed for aliphatic and alicyclic hydrocarbon solvents and toluene. This study did not support associations for solvent exposure and CLL. Observed weak associations for methylene chloride, perchloroethylene, 1,1,1‐trichloroethane exposures, aliphatic and alicyclic hydrocarbons and toluene were not consistent across sexes, and showed no gradient with amount of exposure.     

Occupational asbestos exposure and risk of esophageal,gastric and colorectal cancer in the prospective Netherlands Cohort Study

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 = 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 multivariable‐adjusted 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.     

Occupational exposure to arsenic and risk of nonmelanoma skin cancer in a multinational European study

Occupational studies show a high risk of lung cancer related to arsenic exposure by inhalation; however, only a few studies, and with conflicting results, previously examined a potential link between arsenic exposure at work and skin cancer. The aim of this study is to assess airborne arsenic exposures at the workplace and to quantify associations with nonmelanoma skin cancer (NMSC). The study sample consists of 618 incident cases of NMSC and 527 hospital‐based controls aged 30–79 years from Hungary, Romania and Slovakia. Exposures were evaluated by local experts using occupational histories. Information on host factors and other exposures was collected and used to adjust the associations of interest using multivariable logistic regression. The lifetime prevalence of exposure to work‐related arsenic is 23.9% for cases and 15.5% for controls. No significant association between arsenic exposure in the workplace and NMSC was detected, although an increased adjusted odd ratio was observed for participants with higher cumulative lifetime workplace exposure to arsenic in dust and fumes compared to referents [odds ratios (OR) = 1.94, 95% confidence interval (CI) = 0.76–4.95]. There is evidence for modification of the workplace arsenic–NMSC association by work‐related sunlight exposure in women, with a markedly increased adjusted OR in the presence of workplace sunlight exposure (OR = 10.22, 95% CI = 2.48–42.07). Workplace coexposure to arsenic and sunlight may thus pose an increased risk of NMSC.     

Birth characteristics and Wilms tumors in children in the Nordic countries: A register‐based case–control study

Little is known about causes of Wilms tumor. Because of the young age at diagnosis, several studies have looked at various birth characteristics. We conducted a registry‐based case–control study involving 690 cases of Wilms tumor aged 0–14 years, occurring in Denmark, Finland, Norway or Sweden during 1985–2006, individually matched to five controls drawn randomly from the Nordic childhood population. Information on birth characteristics was obtained from the population‐based medical birth registries. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression analysis. We observed a distinct association between Wilms tumor and high birth weight (≥4 kg) for girls (OR 1.97, CI 1.50–2.59) but not for boys (1.04, 0.78–1.38); overall, the OR was 1.43 (1.17–1.74). Among girls, risk increased by 28% (15–42%) per 500 g increase in birth weight. Large‐for‐gestational age girls also had a higher risk (2.48, 1.51–4.05), whereas no effect was seen for boys (1.12, 0.60–2.07). An association was seen with Apgar score at 5 min < 7 for both sexes combined (5.13, 2.55–10.3). ORs close to unity were seen for parental age and birth order. In our large‐scale, registry‐based study, we confirmed earlier observations of an association between high birth weight and risk of Wilms tumor, but we found an effect only in girls. The higher risk of infants with low Apgar score might reflect hypoxia causing cell damage, adverse side effects of neonatal treatment or reverse causation as low Apgar score might indicate the presence of a tumor.     

Pregnancy complications and subsequent breast cancer risk in the mother: a Nordic population‐based case–control study

Certain features of pregnancy are important risk factors for breast cancer, such as protection afforded by young age at first birth. Preeclampsia, a pregnancy complication, is associated with reduced maternal breast cancer risk. However, questions remain regarding causality, biological mechanisms and the relation of other hypertensive conditions to risk. We conducted a population‐based case–control study of breast cancer cases (n = 116,196) in parous women identified through linkage of birth and cancer registries in Denmark, Finland, Norway and Sweden (1967–2013), including up to 10 matched controls per case (n = 1,147,192) sampled from the birth registries (complete data were not available on all variables). Odds ratios (ORs) with 95% confidence intervals (CIs) were derived from unconditional logistic regression models including matching factors (country, maternal birth year) and parity. Hypertension diagnosed before pregnancy (OR 0.87; 95% CI 0.78–0.97), gestational hypertension (OR 0.90; 95% CI 0.86–0.93) and preeclampsia (OR 0.91; 95% CI 0.88–0.95) were associated with reduced breast cancer risk. Results remained similar after adjustment for smoking and maternal body mass index before first pregnancy, and were generally similar stratified by parity, age at breast cancer diagnosis, time since first and last birth, sex of the offspring and calendar time. Except for retained placenta (OR 1.14; 95% CI 0.98–1.32), no other pregnancy complication appeared associated with breast cancer risk. The mechanisms mediating the modest risk reductions for history of preeclampsia or hypertension preceding or arising during pregnancy, and possible increased risk with history of retained placenta are unknown and warrant further laboratory, clinical and epidemiological investigation.     

Life course sun exposure and risk of prostate cancer: Population‐based nested case‐control study and meta‐analysis

There is currently no means of primary prevention for prostate cancer. Increased exposure to ultraviolet‐radiation may be protective, but the literature is inconclusive. We investigated associations of life course exposure to sunlight with prostate cancer. The study design was a UK‐wide nested case‐control study, based on 1,020 prostate specific antigen‐detected cases and 5,044 matched population controls and a systematic review with meta‐analysis. Men with olive/brown skin (OR = 1.47; 95% CI: 1.00 to 2.17), men who burnt rarely/never (OR = 1.11; 0.95 to 1.29) and men with the lowest levels of intense sun exposure in the 2 years prior to diagnosis (OR = 1.24; 1.03 to 1.50) had an increased prostate cancer risk. However, amongst men with prostate cancer, spending less time outside was associated with a reduced risk of advanced cancer (OR = 0.49; 0.27 to 0.89) and high Gleason grade (OR = 0.62; 0.43 to 0.91), and men who burnt rarely/never had a reduced risk of advanced cancer (OR = 0.71; 0.47 to 1.08). The meta‐analysis provided weak evidence that men with the lowest (versus highest) sunlight exposure had an increased prostate cancer risk (4 studies, random‐effects pooled relative risk = 1.13; 0.98 to 1.29) and higher advanced or fatal prostate cancer risk (6 studies, random‐effects pooled relative risk = 1.14; 0.98 to 1.33). Our data and meta‐analyses provide limited support for the hypothesis that increased exposure to sunlight may reduce prostate cancer risk. The findings warrant further investigation because of their implications for vitamin D chemoprevention trials. © 2009 UICC     

Dietary acrylamide intake and risk of esophageal cancer in a population‐based case‐control study in Sweden

Acrylamide is a potential carcinogen, which commonly occurs in some food items. The relation between acrylamide and esophageal cancer deserves attention. In a Swedish nationwide, population‐based case‐control study, data were collected on diet among other variables in 1995–1997 through personal interviews. Included were 189 cases of esophageal adenocarcinoma (participation rate 88%), 262 cases of gastroesophageal junctional adenocarcinoma (84%), 167 cases of esophageal squamous cell carcinoma (73%), and 820 control participants (73%). Dietary intake of acrylamide exposure was assessed from a food‐frequency questionnaire and categorized into quartiles based on the consumption among the control participants. Unconditional logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI), with multivariable adjustment for known risk factors. Among participants in the highest quartile of acrylamide exposure compared to the lowest, the adjusted risk of all esophageal tumors combined was increased (OR 1.23; 95% CI 1.02–1.75), particularly among overweight or obese persons (OR 1.88; 95% CI 1.06–3.34). Increased point risk estimates were found for each type of esophageal cancer, but the association with esophageal squamous cell carcinoma seemed stronger and was statistically significant, particularly among nonsmokers in the highest quartile of acrylamide exposure (adjusted OR 2.82; 95% CI 1.16–6.87). Regarding squamous cell carcinoma only, a dose‐response association was identified (p for trend 0.01). Dietary intake of acrylamide might be a risk exposure for esophageal cancer, a stronger association among overweight or obese persons was indicated.     

Occupation and larynx and hypopharynx cancer: a job-exposure matrix approach in an international case-control study in France,Italy, Spain and Switzerland

Objective: To investigate the effect of exposure to occupational agents on the risk of hypopharyngeal/laryngeal cancer. Methods: Case-control study conducted during 1979–1982 in six centres in South Europe. An occupational history and information on exposure to non-occupational factors were collected for 1010 male cases of hypopharyngeal/laryngeal cancer as well as for 2176 population controls. The exposure to 10 occupational agents was assessed through a job-exposure matrix. As occupational histories had been collected since 1945 major analyses were restricted to subjects aged less than 55 years (315 cases and 819 controls). Results: Significant elevated risks adjusted for non-occupational variables (smoking, alcohol consumption and diet) and other occupational exposures were consistently found for organic solvents (odds ratio (OR) for ever-exposure: 1.7, 95% confidence interval: 1.1–2.5) and asbestos (OR: 1.6, 1.0–2.5). A significant positive trend for both probability of exposure and duration was found for exposure to solvents. A positive association between exposure to formaldehyde and laryngeal cancer was also suggested. No association was found for exposure to arsenic and compounds, chromium and compounds, and polycyclic aromatic hydrocarbons. Analyses restricted to subjects aged 55 or more did not show elevated risks, with the exception of wood dust (OR: 1.8, 1.3-2.7). Conclusions: In our study occupational exposure to solvents was associated with an increased risk of hypopharyngeal/laryngeal cancer. Results also provide additional evidence of an excess of risk for exposure to asbestos.     

Flavonoid intake and ovarian cancer risk in a population‐based case‐control study

Several recent studies have evaluated the association between dietary flavonoid intake and ovarian cancer risk, and all reported significant or suggestive inverse associations with certain flavonoids or flavonoid subclasses; however, most of these studies were small to moderate in size. We, therefore, examined this association in a large, population‐based case‐control study. We calculated intake of 5 common dietary flavonoids (myricetin, kaempferol, quercetin, luteolin, and apigenin), as well as total intake of these flavonoids, for 1,141 cases and 1,183 frequency‐matched controls. We used unconditional logistic regression to estimate the relative risk (RR) of ovarian cancer for each quintile of flavonoid intake when compared with the lowest quintile. We did not observe an association between total flavonoid intake and ovarian cancer risk. The multivariable‐adjusted RR for the highest versus lowest quintile of total flavonoid intake was 1.06 (95% confidence interval [CI] = 0.78–1.45). In analyses of each individual flavonoid, only intake of apigenin was associated with a borderline significant decrease in risk (RR, highest vs. lowest quintile = 0.79, 95% CI = 0.59–1.06; p‐trend = 0.26), and this association was significant after adjustment for intake of the other 4 individual flavonoids (comparable RR = 0.72, 95% CI = 0.53–0.98; p‐trend = 0.09). These results provide limited support for an association between flavonoid intake and ovarian cancer risk. However, given the findings of previous studies and the biologic plausibility of this association, additional studies are warranted. © 2008 Wiley‐Liss, Inc.     

Poor oral health is associated with an increased risk of esophageal squamous cell carcinoma ‐ a population‐based case‐control study in China

To further examine the association between oral hygiene and esophageal squamous cell carcinoma (ESCC) risk and the effect modification of other exposures, we conducted a population‐based case‐control study between 2010 and 2012 in Taixing, China, a high‐risk area for ESCC. Cases were primarily recruited from endoscopy units at local hospitals, supplemented by linkage to the local Cancer Registry. Control subjects were frequency matched to cases by sex and age (5‐year groups) and were randomly selected from the Taixing Population Registry. For the current analysis, data from 616 histopathologically confirmed cases and 770 controls with complete information on oral hygiene were analyzed. Unconditional logistic regression models, including oral hygiene indicators and potential behavioral confounders, were used to derive odds ratios (ORs) and 95% confidence intervals (CIs). Tooth loss was only marginally significantly associated with ESCC risk (yes vs. no, OR = 1.29, 95% CI 0.94–1.74). However, the excess risk increased with increasing numbers of lost teeth (more than 6 teeth lost vs. none, OR = 1.48, 95% CI 1.04–2.11). Tooth brushing once or less per day, compared with tooth brushing twice or more per day, was associated with a 1.81‐fold increased risk of ESCC. In the stratification analyses, the increased risks associated with these indicators of oral health were more pronounced in older subjects (age ≥ 70 years), women, non‐smokers, and non‐drinkers. Further studies are warranted to verify these findings and to explore the underlying mechanisms, e.g., changed oral microbiota, associated with poor oral hygiene.     

A population‐based cohort study on the use of hormone treatment and endometrial cancer in southern Sweden

Our aim was to determine the risk of endometrial cancer associated with long‐term use of combined hormone therapy (HT) and low‐potency estrogens. In this prospective population‐based cohort, 40,000 women aged 25–64 years, without prior cancer or hysterectomy, were included. The women answered 2 questionnaires at a 10‐year interval regarding HT use and personal details. Women were followed up for an average of 15.5 years through the National Cancer and Causes of Death Registry, representing 236,611 women years. Among the 17,822 postmenopausal women included, 166 cases of endometrial cancer were diagnosed. Only use of combined HT was related to a decreased risk of endometrial cancer (OR 0.3, 95% CI 0.1–0.8), the protective effect was found after 2 years, and increased with extended duration of use. “Only use” of low‐potency estrogens increased the risk of endometrial cancer almost to the same extent as use of high‐potency estrogens (OR 2.0, 95% CI 1.1–3.6 vs. OR 2.5, 95% CI 1.3–4.8), the increased risk was confined to non‐obese women in both groups. The risk was significantly increased for oral but not for local low‐potency estrogen users (OR 2.1, 95% CI 1.1–3.6 vs. OR 1.5, 95% CI 0.4–6.2, respectively). In long‐term estrogen users the risk was highest during the first 2 years, dropping slightly thereafter. Since low‐potency estrogen use increases the risk of endometrial cancer almost as much as high‐potency estrogen use, they should only be given if medically indicated. © 2009 UICC