As compared to the 1996 follow-up (Pira et al, 2005
), in this updated analysis there were 31 additional deaths from pleural and peritoneal mesothelioma (total 68), and 29 additional deaths from lung cancer (total 109), allowing examination of the role of first and subsequent asbestos exposures in this factory on mesothelioma and lung cancer risk. The SMR of pleural/peritoneal mesothelioma continued to use in the years 1996–2004, the total number of such deaths having almost doubled. Thus, the overall SMR for all mesotheliomas (pleural and peritoneal) rose from 3139 in 1946–1996 to 6792 in 1997–2004. This points to longer latency as the key factor in mesothelioma risk, consistent with models that describe incidence as a power function of time since first asbestos exposure (Peto et al, 1982
). For lung cancer, the SMR only changed modestly from 282 to 310 over the last 8 years considered. The appreciable fall in asbestos exposures since the early 1970s in the factory (Pira et al, 2005
) and the cessation of exposure in 1984 may have contributed to this levelling of lung cancer risk, and further supports the view that time-related factors involved in mesotheliomas and lung cancers differ.
When we stratified our data according to the period at first employment, direct trends emerged with latency. In 1968 the acquisition of a nearby asbestos manufacture factory with movement of some of workers between plants and hence a lack of information on previous exposures of these subjects might explain the inconsistent results. Although an occupational history was not taken, any available data on other asbestos-related employments were recorded. The elevated risks of mesothelioma found with latency <15 years (SMR=685) and age at first employment
40 years (SMR=1943) are likely to be due to previous asbestos exposures in other occupational settings. In fact, both subjects who died from pleural mesothelioma before 15 years after first employment had previous job-related exposures. Past asbestos exposure was also recorded for another worker reporting first employment in the plant after 40 years of age. Thus, mesothelioma risk for a late age at first exposure was overestimated.
The excess of laryngeal cancer in our data is in agreement with a report from the US Institute of Medicine (IOM, 2006
), which concluded that there is sufficient evidence for an association between asbestos exposure and laryngeal cancer. This was based both on the consistency of findings of epidemiological studies and the biological plausibility of such an association.
Some studies of occupational asbestos exposures reported increases in risk of digestive, kidney and ovarian cancers, but results have been inconsistent (Doll and Peto, 1985
; Seidman et al, 1986
; IARC, 1987
; Smith et al, 1989
; Berry et al, 2000
; Reid et al, 2004
), and the evidence was later considered suggestive but not sufficient (IOM, 2006
). We found increased mortality from ovarian and liver cancers. Misdiagnosis of peritoneal cancers (La Vecchia, 2001
; Boffetta, 2007
) may explain the excess of ovarian (as well as the small excess of intestinal) cancer deaths, and misdiagnosis of secondaries that of liver cancer. Our findings weigh against an association between asbestos and kidney cancer.
Using mortality data from the province of Turin, when available (ie for years 1980–2000) (ASL 5, 2004
), we found the SMRs of pleural cancer were lower, particularly in women, than those using national reference rates, but were still extremely high (2039 in men, 6431 in women and 3414 overall). Corresponding data for peritoneal cancer were not available. For lung as well as for many other cancer sites of interest, rates in Turin do not appreciably differ from Italian ones, and thus risk estimates were almost unchanged (SMRs of lung cancer were 268 in men, 629 in women and 313 overall). The higher mesothelioma SMRs in women than men are likely to be attributable to the lower baseline rates in women.
Among possible sources of bias, is the validity of SMRs, as a risk indicator (Rothman and Greenland, 1998
; Goldman and Brender, 2000
). Direct standardisation is preferable in general (MacMahon and Trichopoulos, 1996
), but inappropriate here because of the relatively small number of mesothelioma deaths (68). Cohort studies may also underestimate the true risk when SMRs are large (Jones and Swerdlow, 1998
). Strengths of our study are the long period of observation, the small number of individuals lost to follow-up, and the inclusion of many women (Boffetta, 2007
). Further, many subjects (particularly women) had been exposed to large amounts of asbestos dusts for short time periods (Pira et al, 2005
), thereby allowing separation of the roles of early from that of later exposure.
The main finding of this study was that, for pleural and peritoneal cancers, the SMR did not increase in subjects reporting both earlier and later asbestos exposures. In fact, they were similar for those employed only before 30 years and for those employed both before 30 and after 39 years, whereas the lower risks in subjects with an older age at first employment are attributable to shorter latency. In contrast, for lung cancer subsequent exposures led to appreciable increments in relative risks.