Smoking and susceptibility to rheumatoid arthritis in a Swedish population-based case–control study

Smoking is one of the most established risk factors for rheumatoid arthritis (RA). The aim of this study was to estimate how age at smoking debut, smoking cessation, duration, intensity, and cumulative dose of smoking influence the risk of developing anti-citrullinated peptide antibodies (ACPA) positive and ACPA negative RA. The present report is based on a Swedish population-based, case–control study with incident cases of RA (3655 cases, 5883 matched controls). Using logistic regression models, subjects with different smoking habits were compared regarding risk of developing the two variants of RA, by calculating odds ratios (OR) with 95% confidence intervals (CI). Smoking increased the risk of developing both ACPA positive (OR 1.9, 95% CI 1.7–2.1) and ACPA negative RA (OR 1.3, 95% CI 1.2–1.5). For both subsets of RA, there seemed to be a threshold (~ 2.5 pack years for ACPA positive RA and ~ 5 pack years for ACPA negative RA) below which no association between smoking and RA occurred. A dose–response association was observed between cumulative dose of smoking and risk of developing ACPA positive RA (p value for trend < 0.0001). Duration of smoking had a higher influence on the association between smoking and RA than did intensity of smoking. For both subsets of RA, the detrimental effect of smoking decreased after smoking cessation. Twenty years after smoking cessation, there was no longer an association between smoking and risk of ACPA negative RA, whereas the association between smoking and ACPA positive RA risk persisted and was dependent on the cumulative dose of smoking. Smoking increases the risk of both subsets of RA with a more pronounced influence on the risk of ACPA positive RA. Preventive measures in order to reduce smoking are essential and may result in a decline in RA incidence.     

Residential exposure to overhead high-voltage lines and the risk of testicular cancer: results of a population-based case–control study in Hamburg (Germany)

Background: In a population-based case–control study we examined the association between residential exposure to overhead high-voltage lines and testicular cancer. Methods: We recorded the residential biography of cases with testicular cancer identified by the Hamburg Cancer Registry and of controls that were randomly selected from the mandatory registry of residents in Hamburg. The study included 145 incident cases between 15 and 69 years of age, diagnosed between 1995 and 1997, and 313 controls, matched for age in 5-year strata. In model A, exposure was defined by distance (ever vs never). Model B took into account residence time and the inverse distance from the nearest high-voltage line. It distinguished between low and high exposure, the never exposed persons serving as a reference group. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated by unconditional logistic regression. For men below the age of 40 years and men aged 40 years and over separate analyses were carried out. Results: Within a corridor of 100 m the prevalence of exposure to high-voltage lines in Hamburg was 6.9% in cases and 5.8% in controls (OR=1.3; 95% CI=0.56–2.80). In the more complex model B we found an OR of 1.2 (95% CI=0.60–2.47) for low exposure and 1.7 (95% CI=0.91–3.32) for high exposure. Younger men show slightly increased risks in both models. Conclusions: In all, residential exposure to high-voltage lines did not seem to be a major risk factor for testicular cancer in our study. Yet, the fact that risks for men below the age of 40 years were slightly increased in both exposure models deserves further attention.     

Lifetime total physical activity and prostate cancer risk: a population-based case–control study in Sweden

The etiologic role of physical activity in prostate cancer development is unclear. We assessed the association between lifetime total physical activity and prostate cancer risk in a Swedish population-based case–control study comprising 1,449 incident prostate cancer cases and 1,118 unaffected population controls. Information regarding physical activity was obtained via a self-administered questionnaire assessing occupational, household, and recreational activity separately at various ages throughout an individual’s lifetime. Clinical data (TNM-classification, Gleason sum and PSA) was obtained from linkage to the National Prostate Cancer Registry. Overall, we observed no association between lifetime total physical activity and prostate cancer risk (odds ratio [OR] = 1.04, 95% confidence interval [CI] = 0.77–1.41 for ≥49.7 vs. <41.9 metabolic equivalent-hours per day). There was a significantly increased risk of prostate cancer in the most active men compared with the least active men in household (OR = 1.44, 95% CI = 1.08–1.92) and recreational physical activity (OR = 1.56, 95% CI = 1.16–2.10). Comparing the most active with the least active men, total physical activity was not associated with either localized disease (OR = 0.95, 95% CI = 0.67–1.34) or advanced disease (OR = 1.19, 95% CI = 0.83–1.71). These findings do not support the hypothesis that physical activity uniformly protects against prostate cancer development.     

Omega-3 and omega-6 fatty acid intakes and endometrial cancer risk in a population-based case–control study

Purpose

Animal and laboratory studies suggest that long-chain omega-3 (n-3) fatty acids, a type of polyunsaturated fat found in fatty fish, may protect against carcinogenesis, but human studies on dietary intake of polyunsaturated fats and fish with endometrial cancer risk show mixed results.

Methods

We evaluated the associations between endometrial cancer risk and intake of fatty acids and fish in a population-based sample of 556 incident cancer cases and 533 age-matched controls using multivariate unconditional logistic regression methods.

Results

Although total n-3 fatty acid intake was not associated with endometrial cancer risk, higher intakes of eicosapentaenoic (EPA 20:5) and docosahexaenoic (DHA 22:6) fatty acids were significantly associated with lower risks (OR = 0.57, 95 % CI: 0.39–0.84; OR = 0.64, 95 % CI: 0.44–0.94; respectively) comparing extreme quartiles. The ratio of n-3:n-6 fatty acids was inversely associated with risk only on a continuous scale (OR = 0.84, 95 % CI: 0.71–0.99), while total fish intake was not associated with risk. Fish oil supplement use was significantly associated with reduced risk of endometrial cancer: OR = 0.63 (95 % CI: 0.45–0.88).

Conclusions

Our results suggest that dietary intake of the long-chain polyunsaturated fatty acids EPA and DHA in foods and supplements may have protective associations against the development of endometrial cancer.     

Chronic bronchitis and pesticide exposure: a case–control study in Lebanon

Objective Pesticides are widely used toxics. The objective of the study is to evaluate the odds of exposure to pesticides in chronic bronchitis patients.Methods Using the American Thoracic Society standardized questionnaire confirmed by medical diagnosis of chronic bronchitis, a case–control study was␣performed in Lebanon. Pesticide exposure was estimated and between groups comparison was made.Results The study involved 262 controls and 110 chronic bronchitis outpatient subjects from 10 medical centers. Any exposure to pesticides was associated to chronic bronchitis (OR = 2.46 [1.53–3.94]; p < 10⁻⁴). Occupational use presented the highest association (15.92 [3.50–72.41]; p < 10⁻⁴), followed by regional exposure (3.70 [2.05–6.70]; p < 10⁻⁴). Results were confirmed by multivariate and subgroup analysis.Conclusion Pesticide exposure was associated with chronic bronchitis in Lebanese adults. Pesticides toxicological effects may explain chronic respiratory effects associations found with all exposure types.     

Breast cancer risk and night shift work in a case–control study in a Spanish population

Epidemiologic and animal data indicate that night shift work might increase the risk for breast cancer. We evaluated the association of night work with different clinical types of breast cancer in a population based case–control study (MCC-Spain study) taking into account chronotype, an individual characteristic that may relate to night shift work adaptation. Lifetime occupational history was assessed by face-to-face interviews and shift work information was available for 1708 breast cancer cases and 1778 population controls from 10 Spanish regions, enrolled from 2008 to 2013. We evaluated three shift work domains, including shift work type (permanent vs rotating), lifetime cumulative duration and frequency. We estimated odds ratios (OR) for night work compared to day work using unconditional logistic regression models adjusting for confounders. Having ever worked permanent or rotating night shift was associated with an increased risk for breast cancer compared to day workers [odds ratio (OR) 1.18; 95 % CI 0.97, 1.43]. Chronotype was differentially associated with breast cancer depending on the duration of night shift work. Risk was higher in women with invasive tumors (OR 1.23; 95 % CI 1.00, 1.51) and for estrogen and progestagen positive tumors among premenopausal women (OR 1.44; 95 % CI 1.05, 1.99). Having ever performed night shift was associated with a small increased risk for breast cancer and especially in subgroups of women with particular hormone related characteristics.     

Patterns of bias due to differential misclassification by case–control status in a case–control study

BACKGROUND: Case-control study is still one of the most commonly used study designs in epidemiological research. Misclassification of case-control status remains a significant issue because it will bias the results of a case-control study. There exist two types of misclassification, differential versus nondifferential. It is commonly accepted that nondifferential misclassification will bias the results of the study towards the null hypothesis. Conversely, no reports have assessed the impact and direction of differential misclassification on odds ratio (OR) estimate. The goal of the present study is to demonstrate by statistical derivation that patterns exist on the bias induced by differential misclassification. METHODS: Based on a 2 x 2 case-control study design, we derive the odds ratio without misclassification, and those with misclassification according to: (1) controls are misclassified as cases by exposure status; (2) cases are misclassified as controls by exposure status; and (3) both controls and cases are misclassified by exposure status simultaneously. Furthermore, mathematical derivations are shown for each of the ratios of the two odds ratios with and without misclassification. These methods are carried out by simulation analyses. RESULTS: Simulation analyses show that quite a number of biased odds ratios tend to move away from the null hypothesis and result in approaching zero or infinity with increasing proportion of misclassification among cases, controls, or both. These patterns are associated with the exposure status and the values of unbiased odds ratio (<1, 1, or >1). CONCLUSIONS: Our findings suggest that, unlike nondifferential misclassification, differential misclassification of case-control status in a case-control study may not weaken the exposure-outcome association towarding the null hypothesis. Care needs to be taken for interpreting the results of a case-control study when there exists differential misclassification bias, a practical issue in epidemiological research.     

Tea consumption and lung cancer risk: A meta-analysis of case–control and cohort studies

ObjectiveRecent epidemiologic studies, especially cohort and case–control studies, have yielded inconsistent findings regarding the association between tea consumption and risk for lung cancer. The aim of this study was to assess a potential relationship between tea consumption and the incidence of lung cancer worldwide.MethodsA systematic literature search of PubMed, Web of Science, the Cochrane Library, Google Scholar, the Chinese Biomedical Database, and Wanfang Database was conducted from 1966 to January 2014 by two investigators. All cohort studies and case–control studies that evaluated the association of tea and lung cancer were included. Summary relative risks (RR) and the corresponding 95% confidence intervals (CIs) were calculated using a random-effects model. Quality assessments were performed using the Newcastle–Ottawa Scale. Heterogeneity was assessed using the Q and I² tests, and the source of heterogeneity was detected by meta-regression analysis. Publication bias was evaluated with Egger's regression symmetry test. Subgroup analyses and sensitivity analysis were performed.ResultsThirty-eight lung cancer studies (26 case–control studies and 12 cohort studies) with 59,041 cases and 396,664 controls were included. Overall tea consumption was significantly associated with decreased risk for lung cancer (RR, 0.78; 95% CI, 0.70–0.87). Subgroup analyses showed that tea consumption was associated with reduced risk for lung cancer in women (RR, 0.76; 95% CI, 0.62–0.93), case–control studies (RR 0.72; 95% CI 0.63–0.83), Western studies (RR, 0.85; 95% CI, 0.75–0.97), and studies in China and Japan (RR, 0.74; 95% CI, 0.62–0.88). Both green tea (RR, 0.75; 95% CI, 0.62–0.91) and black tea (RR, 0.82; 95% CI, 0.71–0.94) were significantly associated with reduced lung cancer risk. No significant association was found in men or in cohort studies.ConclusionTea consumption may offer some protection against lung cancer.     

Experience with multiple control groups in a large population-based case–control study on genetic and environmental risk factors

We discuss the analytic and practical considerations in a large case–control study that had two control groups; the first control group consisting of partners of patients and the second obtained by random digit dialling (RDD). As an example of the evaluation of a general lifestyle factor, we present body mass index (BMI). Both control groups had lower BMIs than the patients. The distribution in the partner controls was closer to that of the patients, likely due to similar lifestyles. A statistical approach was used to pool the results of both analyses, wherein partners were analyzed with a matched analysis, while RDDs were analyzed without matching. Even with a matched analysis, the odds ratio with partner controls remained closer to unity than with RDD controls, which is probably due to unmeasured confounders in the comparison with the random controls as well as intermediary factors. However, when studying injuries as a risk factor, the odds ratio remained higher with partner control subjects than with RRD control subjects, even after taking the matching into account. Finally we used factor V Leiden as an example of a genetic risk factor. The frequencies of factor V Leiden were identical in both control groups, indicating that for the analyses of this genetic risk factor the two control groups could be combined in a single unmatched analysis. In conclusion, the effect measures with the two control groups were in the same direction, and of the same order of magnitude. Moreover, it was not always the same control group that produced the higher or lower estimates, and a matched analysis did not remedy the differences. Our experience with the intricacies of dealing with two control groups may be useful to others when thinking about an optimal research design or the best statistical approach.     

Dietary patterns and breast cancer risk among women in northern Tanzania: a case–control study

Background

Breast cancer is the second most common cancer among women in the Kilimanjaro Region of Tanzania. It was tested within a case–control study in this region whether a specific dietary pattern impacts on the breast cancer risk.

Methods

A validated semi-quantitative Food Frequency Questionnaire was used to assess the dietary intake of 115 female breast cancer patients and 230 healthy age-matched women living in the same districts. A logistic regression was performed to estimate breast cancer risk. Dietary patterns were obtained using principal component analysis with Varimax rotation.

Results

The adjusted logistic regression estimated an increased risk for a “Fatty Diet”, characterized by a higher consumption of milk, vegetable oils and fats, butter, lard and red meat (OR = 1.42, 95 % CI 1.08–1.87; P = 0.01), and for a “Fruity Diet”, characterized by a higher consumption of fish, mango, papaya, avocado and watery fruits (OR = 1.61, 95 % CI 1.14–2.28; P = 0.01). Both diets showed an inverse association with the ratio between polyunsaturated and saturated fatty acids (P/S ratio).

Conclusion

A diet characterized by a low P/S ratio seems to be more important for the development of breast cancer than total fat intake.     

Moderate physical activity and prostate cancer risk: A case–control study in china

A case-control study was conducted to investigate the association between physical activity and prostate cancer risk in China. A total of 130 recent histopathologically confirmed cancer cases and 274 controls were interviewed. Information collected included type, intensity and duration of various physical activities. The adjusted odds ratios of prostate cancer risk for physical activity variables were obtained from multivariate logistic regression models. Results showed that moderate physical activity was inversely related to the prostate cancer risk, with adjusted odds ratio being 0.20 (95% confidence interval 0.07–0.62) for the upper vs. the lower quartiles of weekly metabolic equivalent task-hours. The dose-response relationship was also significant (p = 0.015). The findings suggest that moderate physical activity may be protective against prostate cancer for Chinese men.This revised was published online in April 2005. In the previous version the article category was missing.     

Asbestos exposure and malignant lymphoma: a multicenter case–control study in Germany and Italy

Aims

To analyze the relationship between asbestos exposure and malignant lymphoma in a multicenter case–control study conducted in Germany and Italy according to a common core protocol.

Methods

Male and female patients with malignant lymphoma (n = 1,034) between 18 and 80 years of age were prospectively recruited in six study areas in Germany (Ludwigshafen/Upper Palatinate, Heidelberg/Rhine-Neckar-County, Würzburg/Lower Frankonia, Hamburg, Bielefeld/East Westphalia, and Munich) and in two study areas in Sardinia, Italy (Cagliari and Nuoro provinces). A total of 1,173 population control subjects were drawn from population registers. In a structured personal interview, we elicited a complete occupational history, including every occupational period that lasted at least 1 year. On the basis of job task-specific supplementary questionnaires, trained experts assessed the exposure to asbestos. As a measure of cumulative asbestos exposure on a time by intensity scale, fiber-years were calculated. 12 cases (1.2%) and 12 control subjects (1.0%) had a cumulative asbestos exposure of more than 2.6 fiber-years (highest exposure category according to the 90th percentile of exposed control subjects). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression analysis adjusted for age, sex and study region. Patients with specific lymphoma sub-entities were additionally compared with the entire control group.

Results

We observed no statistically significant association between cumulative asbestos exposure and the risk of any lymphoma subtype. An elevated risk was found for the association between exposure to more than 2.6 fiber-years and multiple myeloma (OR = 6.0; 95% CI 1.4–25.1); however, numbers were small (n = 3 cases, all of them from Italy; n = 12 control subjects).

Conclusions

Our study does not support an association between asbestos exposure and risk of malignant lymphoma.     

Dietary sugar and lung cancer: A case‐control study in Uruguay

To examine whether dietary sugar modifies lung cancer risk, a case‐control study involving 463 cases with lung cancer and 465 hospitalized controls was conducted in Uruguay in the period 1993–1996. Dietary patterns were assessed in detail using a 64‐item food‐frequency questionnaire, which allowed the calculation of total energy intake. After adjustment for potential confounders through a model that included tobacco smoking and total energy, total fat, vitamin C, and α‐carotene intakes, an increased risk for sugar‐rich foods, total sucrose intake, sucrose‐to‐dietary fiber ratio, and glycemic index for lung cancer was observed (odds ratio for highest category of total sucrose intake = 1.55, 95% confidence interval = 0.99–2.44). When lung cancer was analyzed separately by cell type, odds ratios for small cell and large cell undifferentiated carcinoma were higher than those observed for squamous cell and adenocarcinoma of the lung. The joint effect of pack‐years, total fat intake, and sucrose intake was associated with an increased risk of 28.3 (95% confidence interval = 13.4–59.7) for high values of the three variables. The study suggests that high sucrose intake could be an important risk factor in lung carcinogenesis. Further studies, both epidemiological and experimental, are needed to replicate the present findings and to clarify the mechanism(s) of sucrose intake in lung carcinogenesis.     

Associations between estrogen receptor genetic polymorphisms,smoking status,and prostate cancer risk: a case–control study in Japanese men

Objective

Prostate cancer (PCa) is one of the major causes of death among men. Our study investigated the association of ESR1 and ESR2 genotypes with susceptibility to PCa in relation to smoking status in Japanese.

Method

A case–control study was performed with 750 Japanese prostate cancer patients and 870 healthy controls. After age-matching in case–controls, 352 controls and 352 cases were enrolled in this study. By using logistic regression analysis, the different genotypes from ESR1 and ESR2 were analyzed according to case/control status.

Result

ESR2 rs4986938 AG and AG + AA genotypes were associated with significantly decreased risk of PCa (AG: OR = 0.68, 95 % CI 0.47–0.97, P < 0.05 and AG + AA: OR = 0.67, 95 % CI 0.47–0.94, P < 0.05). However, there was no significant association between ESR1 rs2234693 and PCa risk. When patients were grouped according to smoking status, the ESR2 rs1256049 AA genotype (OR = 0.48, 95 % CI 0.25–0.95, P < 0.05) and ESR2 rs4986938 AG + AA genotype (OR = 0.64, 95 % CI 0.41–1.00, P < 0.05) showed significantly decreased PCa risk in the ever-smoker group.

Conclusion

Our results suggest that the estrogen receptor ESR2 has a very important function to predict PCa and that different SNPs have different predictive values. Smoking may influence estrogenic activity and may influence PCa together with the estrogen receptor.     

Acute myeloid leukaemia and exposure to organic solvents – a case–control study

The objective was to study the relation between exposure to organic solvents and the risk of developing acute myeloid leukaemia (AML) in Caucasians aged 18 years and more. Ninety-eight cases of AML were diagnosed from September 1986 to March 1990 in Novi Sad, Yugoslavia, and in two London hospitals from September 1988 and May 1994 and from July 1992 and July 1994, respectively. Two controls were matched to each case by hospital, year of admission, gender and 5-year age group. Information on solvent exposure was collected by interview. Odds ratios (ORs) were derived with conditional logistic regression. The degree of solvent exposure was determined by three experts blind to the status of the subject with good agreement between them (the coefficient ranged between 0.52 and 0.86). The response rate for cases was 80%. Exposure to solvents was associated with the increased risk of AML (OR: 2.52; 95% CI: 1.45–4.39; p = 0.001) and those with probable exposure to solvents were found to have an odds ratio of AML over three times greater than non-exposed. We also found an elevated OR for exposure to oils (OR: 1.56) but this was not statistically significant. There is no clear pattern of increasing risks with increasing duration of employment but a significant risk was found for exposures of 10 years or less. An induction period of less than 10 years or more than 30 years was associated with a significantly raised OR. There was a significant excess of machinery mechanics and fitters among the cases.     

Dietary cadmium intake and breast cancer risk in Japanese women: A case–control study

Cadmium, an environmental pollutant, may act like an estrogen and be a potential risk factor for estrogen-dependent diseases such as breast cancer. We examined the hypothesis that higher dietary cadmium intake is associated with risk of overall and hormone receptor-defined breast cancer in Japanese women, a population with a relatively high cadmium intake. The study was conducted under a case–control design in 405 eligible matched pairs from May 2001 to September 2005 at four hospitals in Nagano Prefecture, Japan. Dietary cadmium intake was estimated using a food frequency questionnaire. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer and its hormone-receptor-defined subtypes were calculated by tertile of dietary cadmium intake. We found no significant association between dietary cadmium and risk of total breast cancer in either crude or multivariable-adjusted analysis. Adjusted ORs for tertiles of cadmium intake were 1.00, 1.19, and 1.23 (95% CI, 0.76–2.00; P for trend = 0.39) for whole breast cancer. Further, no significant associations were seen across strata of menopausal status, smoking, and diabetes in multivariable-adjusted models except for adjusted OR for continuous cadmium intake in postmenopausal women. A statistically significant association was found for estrogen receptor-positive (ER+) tumors among postmenopausal women (adjusted OR = 1.00, 1.16, and 1.94 [95% CI, 1.04–3.63; P for trend = 0.032]). Although the present study found no overall association between dietary cadmium intake and breast cancer risk, higher cadmium intake was associated with increased risk of ER+ breast cancer in postmenopausal women, at least at regular intake levels in Japanese women in the general population. Further studies are needed to confirm this association.