Nested case-control studies

J2. Jauhiainen, M., Koskinen, P., Ehnholm, C., Heikki Frick, M., Manttari, M., Manninen, V., and Huttunen, J. K., Lipoprotein(a) and coronary heart disease risk A nested case-control study of the Helsinki heart study participants. Atherosclerosis (Shannon, Irel.) 89, 59-76 (1991). 

In a nested case-control study of cancers associated with chemical exposures in the wood industry, Kauppinen et al. (1986) found a significantly increased risk of respiratory system cancer associated with exposure to phenol and phenol in wood dust. As is often the case in occupational settings, these exposures were confounded by smoking and exposures to other materials like pesticides. The increased risk observed for exposure to phenol was almost 5-fold (odds ratio of 4.94), but showed no dose-related increase. This risk dropped to 4-fold with adjustments for smoking history, and to less than 3-fold (and non-significant) when workers exposed to both phenols and pesticides were excluded from the analysis. 

Kauppinen TP, Partanen TJ, Nurminen MM. 1986. Respiratory cancers and chemical exposures in the wood industry A nested case-control study. Br J Ind Med 43 84-90. 

Koro CE, Fedder DO, L ltaUen GJ, et al. Assessment of independent effect olanzapine and risperidone on risk of diabetes among patients with schizophrenia population based nested case-control study. BMJ 2003 326 283. 

Bond GG, Flores GH, Stafford BA, et al Lung cancer and hydrogen chloride exposure results from a nested case control study of chemical workers. J Occup Med 33 958-961, 1991... 

Kilkkinen, A., Virtamo, J., Vartiainen, E., Sankila, R., Virtanen, M.J., Adlercreutz, H., and Pietinen, P., Serum enterolactone concentration is not associated with breast cancer risk in a nested case-control study, Int. J. Cancer, 108, 277, 2004. 

The results of this study were not eonsidered by the Working Group, but it is ineluded because it forms the study base of the nested case-control studies considered. 

Two cohort studies, two proportionate mortality studies and two nested case-control studies looked at cancer mortality or incidence among workers using metalworking fluids with ethanolamines as additives, with or without sodium nitrite. Small excesses were observed for cancers at various sites, in particular, stomach, oesophagus and larynx. In most of these studies, only associations with use of soluble oils or synthetic fluids were presented and no results were given specifically in relation to triethanolamine exposure. It is difficult to draw conclusions regarding triethanolamine using data from studies of exposures to these complex mixtures. 

Baker SG, Kramer BS, Srivastava S. Markers for early detection of cancer statistical guidelines for nested case-control studies. BMC Med Res Methodol 2002 2 4. 

J. Cancer 85 (1999) 596-600 E. M. Ward et al., Serum Organochlorine Levels and Breast Cancer A Nested Case-control Study of Norwegian Women, Cancer Epidemiol. Biomarkers. Prev. 9 (2000) 1557-67 D. Bagga et al., Organochlorine Pesticide Content of Breast Adipose Tissue from Women with Breast Cancer and Control Subjects, J. Natl. Cancer Inst. 92... 

Graham, D. J., D. Campen, R. Hui, M. Spence, C. Cheetham, G. Levy, S. Shoor, and W. A. Ray. 2005. Risk of Acute Myocardial Infarction and Sudden Cardiac Death in Patients Treated With Cyclo-oxygenase 2 Selective and Non-selective Non-steroidal Anti-inflammatory Drugs Nested Case-control Study. Lancet 365 475M81. 

J.D., Neuberg, M., Benn, T, Fannett, B., Pearce, N. Saracci, R. (1995) Soft tissue sarcoma and non-Hodgkin s lymphoma in workers exposed to phenoxy herbicides, chlorophenols, and dioxins two nested case-control studies. Epidemiology, 6, 396-402... 

A nested case-control study within a cohort of rubber workers in the United States was performed to examine the relationship between exposure to solvents and the risk of cancer (Checkoway et al., 1984 Wilcosky et al., 1984). The cohort consisted of 6678 male rubber workers who either were active or retired between 1964 and 1973. The cases comprised all persons with fatal stomach cancer (n = 30), respiratory system cancer (z7 = 101), prostate cancer ( = 33), lymphosarcoma (n = 9) or lymphocytic leukaemia (z7 = 10). These sites were chosen because they were those at which cancers had been found to be in excess in an earlier cohort analysis (McMichael et al., 1976). The controls were a 20% age-stratified random sample of the cohort (z = 1350). Exposure was classified from a detailed work history and production records. An association was observed between exposure for one year or more to carbon tetrachloride and lymphocytic leukaemia (odds ratio (OR), 15.3 / < 0.0001, based on eight exposed cases) and lymphosarcoma (OR, 4.2 p < 0.05, based on six exposed cases) after adjusting for year of birth. The relative risk associated with 24 solvents was examined and levels of exposure were not reported. [The Working Group noted that overlapping exposures limit the ability to draw conclusions regarding carbon tetrachloride.]... 

The risk of cancer from carbon tetrachloride has been examined in five occupational populations. In three of four studies that collected information on non-Hodgkin lymphoma (two cohort investigations and one independent nested case-control study), associations with exposure to carbon tetrachloride were suggested. However, not all of these studies distinguished exposure to carbon tetrachloride specifically, and the associations were not strong statistically. In the fourth study (another cohort investigation), few men were exposed to carbon tetrachloride and the risk of non-Hodgkin lymphoma was not reported. 

A nested case-control study of lung cancer in a cohort of chemical workers showed no association with exposure to carbon tetrachloride. 

Bond, G.G., Flores, G.H., Shellenberger, R.J., Cartmill, J.B., Fishbeck, W.A. Cook, R.R. (1986) Nested case-control study of lung cancer among chemical workers. Am. J. Epidemiol., 124, 53-66... 

Austin and Schnatter (1983a) conducted a cohort study of 6588 white male workers employed at a petrochemical plant in the United States between 1941 and 1977. The study was conducted to investigate a cluster of brain tumours that was reported earlier in the same population (Alexander et al., 1980). There were 765 deaths (SMR, 0.8) and 150 cancer deaths (SMR, 0.9) observed. A greater than expected number (based on national rates) of brain cancers (SMR, 1.6 95% confidence interval (CI), 0.8-2.8, based on 12 cases) was observ ed. Austin and Schnatter (1983b) also conducted a nested case-control study to examine the relationship between the risk of primary brain tumours and exposures at the facility. No significant association with 1,2-dichloroethane exposure was observed. 

Five cohort studies and one nested case-control study of brain tumours have exa-... 

Nested case-control studies for lung (Barbone et al., 1992) and central nervous system (Barbone et al., 1994) neoplasms w ere conducted using the full cohort of dye and resin manufacturing workers reported on by Delzell et al. (1989). Exposure w as assessed on an ordinal scale based on job titles, w ork areas, and potential for contact. When the work histories of 51 lung cancer cases were compared with those of 102 controls matched for year of birth, an association was observed with potential epichlorohydrin... 

Bond et al. (1986) conducted a nested case-control study of lung cancer among a cohort of 19 608 male chemical workers in the United States (Bond et al., 1985). Further details of the study are reported in Section 2.2 of the monograph on carbon tetrachloride in this volume. Ever having been exposed to epichlorohydrin was associated with a decreased risk of lung cancer (odds ratio, 0.3 95% CI, 0.1-0.9 5 exposed cases). 

In the nested case-control study among rubber workers in the United States... 

As part of a nested case-control study that is described more fully in the monograph on phenol (see this volume), Kauppinen et al. (1993) assessed exposure to chlorophenols in 136 men with respiratory cancer and 408 matched controls from a cohort of Finnish woodworkers. Nine cases were classified as exposed (odds ratio, 0.9 90% Cl, 0.4-1.8), and, after adjustment for smoking habits (when known), the risk estimate was little changed. 

In another nested case-control study based on the same cohort, Partanen et al. (1993) compared exposure to chlorophenols and other suspected risk factors in four cases of Hodgkin s disease, eight cases of non-Hodgkin lymphoma, 12 cases of leukaemia and 152 matched referents. Exposures were reconstructed through plant- and period-specific job-exposure matrices. Two of the cases were classed as exposed to chlorophenols (odds ratio, 0.9 95% Cl, 0.2-4.5). 

Nested case-control study of brain cancer in petrochemical industry Nested case-control study of five types of cancer among rubber workers... 

Nested case-control study of central nervous system in nuclear workers... 

Carpenter et al. (1988) carried out a nested case-control study of cancer of the central nervous system among workers at two nuclear facilities located in Tennessee (United States). They identified 89 cases (72 males and 17 females) who had died between 1943 and 1979. Four controls, living at the time the case was diagnosed, were matched to each case. Job history records were scrutinized by an industrial hygienist to assess potential exposure to each of 26 chemicals or chemical groups. Toluene, xylene (see this volume) and 2-butanone (methyl ethyl ketone) were evaluated as one chemical group the matched relative risk was 2.0 (95% confidence interval (Cl), 0.7-5.5 n = 28) in comparison with unexposed workers. Almost all cases had had low exposure, according to the classification used and there was no dose-response trend. The authors stated that the relative risks w ere adjusted for internal and external exposure to radiation. 

Xylene was mentioned as an exposure in four studies. Two were community-based case-control studies, one of which involved brain cancer and one involved several types of cancer. The two industry-based studies were configured as nested case-control studies, one of central nervous system tumours and one of several sites. In none of these studies was xylene the sole or predominant exposure. Cancers at most sites were not significantly associated with xylene exposure in any study. Incidence of colorectal cancer was significantly elevated in the Canadian case-control study, but no other study reported colorectal cancer results. Hodgkin s disease was elevated in one study non-Hodgkin lymphoma was elevated in one study, but not in another. Most results were based on small numbers. In... 

The risk of avascular necrosis has been assessed in a nested case-control study using computer records (268). There were 31 cases during 720 000 person-years Avascular necrosis was strongly associated with glucocorticoid exposure (RR = 16). When total prednisone exposure over 35 months was stratified into three levels (under 440 mg, 440-1290 mg, and over 1290 mg), there was no excess risk for cumulative doses of up to 440 mg (RR = 0 95% Cl = 0, 5). The relative risk was increased for doses between 440 and 1290 mg (RR = 6 Cl = 1, 43) and indeterminately increased at doses over 1290 mg (Cl = 26, infinity). 

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