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The scientific data for the remainder of the cancers and other diseases reviewed by the committee were inadequate or insufficient to determine whether an association exists. For cancers in this category, the available studies are of insufficient quality, consistency, or statistical power to permit a conclusion regarding the presence or absence of an association. For example, studies fail to control for confounding or have inadequate exposure assessment. This group includes hepatobiliary cancers, nasal/nasopharyngeal cancer, bone cancer, female reproductive cancers (cervical, uterine, ovarian), breast cancer, renal cancer, testicular cancer, leukemia, and skin cancer. The scientific evidence for each of these cancers is detailed in Chapter 7. Recent published studies contained enough evidence to warrant moving skin cancer from the limited/suggestive evidence of no association category to this categoty. The scientific evidence for two cancers that are of special interest to the DVA--hepatobiliary cancer and nasopharyngeal cancer--will also be summarized here. Because of its public health importance, breast cancer also receives attention.
Several reproductive effects are classified in this category, including spontaneous abortion, birth defects other than spina bifida, neonatal/infant death and stillbirths, low birthweight, childhood cancer in offspring, and abnormal sperm parameters and infertility. The scientific evidence for reproductive effects is detailed in Chapter 9. Neurobehavioral effects that are classified in this category include cognitive and neuropsychiatric disorders, motor/coordination dysfunction, and chronic peripheral nervous system disorders. The scientific evidence for these effects is detailed in Chapter 10. Other health effects that are classified in this category include metabolic and digestive disorders, immune system disorders, circulatory disorders, and respiratory disorders. The scientific evidence for these effects is detailed in Chapter 11.
On the whole, the estimated relative risks for skin cancer are fairly evenly distributed around the null, and in a number of studies the confidence intervals were relatively narrow. This conclusion led the committee responsible for VAO to conclude that there was limited/suggestive evidence of no association between skin cancer and exposure to herbicides used in Vietnam. One other recent study (Lynge, 1993), however, found an excess risk of skin cancer. Based on four cases, a statistically significant increase in the risk of melanoma was observed in the subgroup of men who had been employed for at least one year, using a ten-year latency period (SIR=4.3, CI 1.2-10.9). However, no information is given about the risk in men with less than 10 years of latency and expected numbers for women are not reported so obserbed elevated risk in the men with 10+ years of latency cannot be put into context. Another study found a significant excess risk in men from the Seveso area (SMR = 3.3), based on only three cases (Bertazzi et al., 1989a,b). The committee felt that these results, while not even suggestive evidence about an association, undermined the evidence of no association in VAO, and thus warranted changing skin cancer to the "inadequate/insufficient evidence to determine whether an association exists" category.
There are relatively few occupational, environmental, and veterans studies of hepatobiliary cancer, and most of these are small in size and have not controlled for lifestyle-related factors. The estimated relative risk in the various studies range from 0.3 to 3.3, usually with broad confidence intervals. Given the methodological difficulties associated with most of these studies, the evidence regarding hepatobiliary cancer is not convincing with regard to either an association or lack of association with herbicides or TCDD. The few studies that have been published since VAO (Asp et al., 1994; Bertazzi et al., 1993; Blair et al., 1993; Collins et al., 1993; and Cordier et al., 1993) do not change the conclusion that there is inadequate evidence to determine whether an association exists between exposure to herbicides and hepatobiliary cancer.
There are only a few occupational studies, one environmental study, and one veterans study of nasal and/or nasopharyngeal cancer, including two recently published studies (Asp et al., 1994, and Bertazzi et al., 1993). The estimated relative risks in the various studies range from 0.6 to 6.7, usually with broad confidence intervals. Thus, there is inadequate/insufficient evidence to determine whether an association exists between exposure to herbicides and nasal/nasopharyngeal cancer.
There have been a few occupational studies, two environmental studies, and two veterans studies of breast cancer among women exposed to herbicides and/or TCDD. These include four recently published studies (Bertazzi et al., 1993; Blair et al., 1993; Dalager et al., 1995; and Kogevinas et al., 1993). Most of these studies reported a relative risk of approximately 1.0 or less, but it is uncertain whether or not the female members of these cohorts had substantial chemical exposure. TCDD appears to exert a protective effect on the incidence of mammary tumors in experimental animals (see Chapter 3), which is consistent with the tendency for the relative risks to be less than 1.0. In summary, however, the committee believes that there is insufficient evidence to determine whether an association exists between exposure to herbicides and breast cancer.
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