Excess relative risk

A difficulty with epidemiologic studies at low doses is the inability to adequately control for potentially confounding factors to the extent necessary to exclude spurious observations, either positive or negative. Epidemiologic studies are not capable of detecting increased responses unless the excess relative risk is on the order of 30 to 40 percent or higher. 

Leukaemia was the first cancer to be linked with exposure to radiation from the atomic bombings at Hiroshima and Nagasaki, Japan. Excess relative risk for leukaemia was higher than for any other neoplasm in bomb survivors and for people exposed as children. Radiation-related leukaemia started to occur two to three years after the bombing, reached its peak within six to eight years, and has declined steadily since then. For people exposed as adults, the excess risk was lower than that of people exposed as children, but the excess risk appears to have persisted throughout the followup period (LARC, 2000). Small increases in childhood leukaemia may also have occurred in some populations that were exposed to... 

The Radiation Effects Research Foundation s Life Span Study of atomic bomb survivors has reported that for all solid tumours combined, there is clear evidence of a radiation dose-response relationship. Both excess relative risk and excess absolute risk are larger for individuals exposed as children than for those exposed as adults, and solid tumour risk continues to increase in later years (Kodama et al., 2003). Survivors of the atomic bombs also have increased risk of all kinds of solid tumours, including those of adult life, although the degree of susceptibility varies with age at the time of the bombings and is generally highest early in life. 

Most cancers from radon were produced by radon daughter decay products (polonium - 3 isotopes bismuth - 1 isotope and lead - 3 isotopes). ERR (excessive relative risks) of cancers varied, ranging from 0.002 to 0.08 per working level months (WLM) of 170 h of exposure. One WLM is about 200 pCi per liter in a home and 300 pCi per liter in an imdergroimd mine. Relative risk increases from 1 to 10 at 2,500 WLM and 16 at twice that exposure level (5,000 WLM) in the Colorado cohort (Harley, 2008). 

Small excess relative risks for buccal cavity and/or pharynx cancer and lung cancer were most consistently observed across these studies. The increases in risk were generally not of statistical significance with the exception of the Blair et al. (1986) report of an SMR of 3.0 (95% CI, 1.3-6.6) for nasopharyngeal cancer. 

Kinjo et al. (1996) compared cancer death rates for a cohort (1,351 cases) of MD survivors with those of a referent population (5,667 subjects) who hved in the same region of Japan and consumed fish daily. After adjusting for age, gender, and length of follow-up period, they found no excess relative risk (RR) for overall mortality, all cancer deaths combined, or all noncancer deaths combined. Analysis of site-specific cancers found that Minamata survivors were less likely to die of stomach cancer than the referent population (RR, 0.49 95% confidence interval (Cl), 0.26-0.94). However, on Ae basis of five observed deaths, survivors were eight times more likely than the referent population to have died from leukemia (RR, 8.35 95% Cl, 1.61-43.3). 

Iodine deficiency may also have had a promoting effect on thyroid cancer development after the Chernobyl accident (Shakhtarin et al, 2003). As a result of this accident, there may have been a combined effect of radiation dose and iodine deficiency in which iodine deficiency doubled the excess relative risk for cancer per Gray (Gy). 

As low as reasonably achievable Beta particles = electrons 95% confidence interval Expected number of cancers in the non-exposed group European Commission Excess relative risk Gamma rays... 

Analyses of radio-epidemiological data, e.g., the A-bomb survivors data, can be based on the assumption of an excess relative risk (ERR) model or an excess absolute risk (EAR) model. The ERR model assumes that the excess risk is proportional to the baseline (or spontaneous) risk, the cancer risk for a person to be diseased with a specific cancer in the absence of radiation. The EAR model expresses the risk as difference in the total risk and the basehne risk. The choice whether the ERR or the EAR model is taken to estimate radiation risks can be a crucial point due to the fact that risk estimates based on an ERR or an EAR model can vary considerably when individual tumor sites are considered. This issue is also called transport (or transfer) of risks from the exposed population to the target population (e.g., from a Japanese to a European population) and corresponds to the question whether the ERR or the EAR is taken to be the same in the exposed population and in the reference population (see below). Section 3.3 elaborates on the issue of radiation risk transfer, and Fig. 7.3 gives an illustration. 

Let us assume that enough information is available regarding the levels of benzene in Mr. Z s well, the number of years he consumed the water, and even his water consumption rate, to derive a reasonably accurate estimate of his cumulative exposure from this source. The epidemiologists and biostatisticians carefully evaluate the dose-response data from the published epidemiology studies used as the basis for classifying benzene as a cause of leukemia. Further assume that we learn from this evaluation that Mr. Z incurred a cumulative benzene exposure approximately equivalent to the cumulative exposure that was found to cause a three-fold excess risk of leukemia in the occupational studies of benzene exposure. A relative risk of three. 

The relative risk is calculated as a measure of response and is then used to calculate the excess lifetime cancer risk expressed as unit risk (associated with a lifetime exposure to 1 p,g/m ). 

Horowitz R, Kotler M, Shufman E, et al (2000) Confirmation of an excess of the high enzyme activity COMT val allele in heroin addicts in a family-based haplotype relative risk study. Am J Med Genet 96 599-603... 

Whatever mathematical model is assumed for the dose-incidence relationship, it is noteworthy that susceptibility can vary markedly with age, so that the radiation-induced cancer excess at various times after irradiation may more nearly approximate a constant percentage of the natural age-specific incidence than a constant number of additional cases, depending on the neoplasm in question. For some individual neoplasms, but not the leukemias, the data do in fact suggest that the "relative risk model is more appropriate than the absolute risk model (see Section 6.1.7). For all neoplasms combined, also, the excess of radiation-induced cases at different times after irradiation approximates more nearly a constant percentage of the age-specific incidence. 

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.]... 

In the Federal Republic of Germany (Thiess et al., 1982), 74 workers were involved in an accident in 1953 in a plant producing 2,4,5-trichlorophenol. Follow-up through 1980 revealed three deaths from stomach cancer, with relative risks of the order of 4-5 depending on the comparison group there was no excess of cancers at other sites combined. 

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