CHAPTER 7

MIGRANT STUDIES

Several epidemiologic studies have compared cutaneous malignant melanoma (CMM) incidence and mortality rates among migrants, among natives of the country adopted by these migrants, and among natives in the countries from which the migrants originated. These investigations have generally indicated that CMM risks among migrants who have moved to sunnier climates are lower than those among the native-born population from the adopted country (Houghton and Viola 1981; Lee 1982). All of the epidemiologic results showed that increasing duration of residence and earlier age at arrival were associated with higher risks of CMM among European-born immigrants to Israel, Australia, and New Zealand (Movshovitz and Modan 1973; Anaise et al. 1978; Katz et al. 1982; Holman et al. 1980; Dobson and Leeder 1982; Holman and Armstrong 1984; Cooke and Fraser 1985). There are no published data on the CMM risk of migrants to less sunny locales. This chapter reviews the available epidemiologic information about the risk of CMM among immigrants.

The earliest studies which identified migrants as a unique population with respect to CMM were conducted in Israel. The Israeli population has largely developed over the last century as a result of substantial immigration from Europe, Asia, and Africa, and thus provided a valuable population for various studies. Three studies using data from Israel's Central Cancer Registry have been conducted (Movshovitz and Modan 1973; Anaise et al. 1978; Katz et al. 1982), with cases overlapping among the studies; therefore, only the most recent study is described.

This most recent Israeli study examined l,050 CMM cases diagnosed from 1960 to 1974 and reported in the Central Cancer Registry (Katz et al. 1982). The authors analyzed incidence rates (based on Central Bureau of Statistics data) by place of birth and length of stay. As shown in Table 7-1, incidence rates among the Israeli-born or the European- and American-born Jews were higher than the rates among Asian- or African-born Jews for all age groups and each average length of residence. The age-categorized incidence rates (see Table 7-1) among the European- and American-born were generally lower than the rates among the Israeli-born except for those immigrants residing in Israel for at least 17 years and in the 15-29 or 65+ age groups, and those living in Israel for an average of 4 years and who were 65+ years of age. The incidence rates among European- and American-born Jews who had lived in Israel for 17+ years consistently exceeded the rates for those who lived in Israel for an average of 13 years but not those in Israel for an average of 4 years. A clearer difference was observed when incidence rates were compared for the period of immigration (before 1947 and after 1948) for European- and American-born Jews. For those diagnosed between 1965 and 1974, the range of average annual incidence rates within 15-year age groups for those immigrating before 1947 was 10.28-12.36/10[5] compared with the range for those immigrating after 1948 (1.09-4.05/10[5]). For cases diagnosed between 1960 and 1964, the differences between those arriving in Israel before 1947 and after 1948 were not nearly as large. Katz et al. (1982) concluded that the higher incidence rates among European- and American-born immigrants compared to the more pigmented immigrants from Middle Eastern countries, and the increasing incidence with length of exposure among the European- and American-born, were "consistent with the cumulative effect of solar radiation as a causative factor."

Beginning in 1980, four detailed studies based on CMM data from Australia and New Zealand were published. Holman et al. (1980) analyzed data on 120 pre-invasive malignant melanoma (PIM) and 422 invasive malignant melanoma (CMM) cases identified in Western Australia from hospital discharge records and pathology lab reports for 1975 and 1976. As shown in Table 7-2, incidence rates (age-standardized to the total population of Western Australia in 1976) were greater among native-born Australian males with PIM and CMM and females with CMM than among British immigrants. Table 7-2 also indicates that rates of CMM among male and female British-born immigrants were about two times greater than all other immigrants combined. The differences in incidence rates were unchanged after adjustment for social class and age. Although their data sources did not provide information on duration of residence, the authors noted that the observed differences in incidence rates would be expected if CMM risks "were proportional to duration of residence in an area of high sun exposure."

Dobson and Leeder (1982) examined data on 2,243 CMM deaths obtained from the Australia Bureau of Statistics for 1968 to 1977. Standardized mortality ratios adjusted for age and country of birth were about two times higher among native-born Australians (124.3 and 118.6 for males and females, respectively) than among immigrants (except immigrants from New Zealand). The standardized mortality ratios among male immigrants ranged from 30.1 for the Netherlands to 71.0 for "elsewhere" (i.e., non-European). Among female immigrants the standardized mortality ratios ranged from 28.4 for Germany to 85.2 for Poland. Among immigrants from England and Ireland, those living in Australia for 24 years or longer had higher mortality rates than those living in Australia for less than 24 years. This finding was consistent in all sex and age groups considered, except for females in age group 20-39. The CMM mortality rates among these immigrants by age, sex, and duration of residence were all less than the comparable mortality rates among native-born Australians. The mortality rates among Australian immigrants of at least 24 years exceeded those rates shown for England and Wales (Lee and Yongchaiyudha 1971, as cited in Dobson and Leeder 1982).

Dobson and Leeder (1982) also compared CMM deaths for English and Irish immigrants (for 1968 to 1977) with deaths from all causes (for 1971) in Australia according to age at arrival, age at death, and sex. For CMM deaths occurring after age 40, the ratio of CMM deaths to deaths from all causes among immigrants generally had an inverse relationship with age (i.e., the earlier the age of arrival, the higher the ratio). For example, males arriving before 10 years of age were about three times more likely to die from melanoma than those who arrived after age 40 and about two times more likely to die from CMM than those arriving between 20 and 39 years of age. Dobson and Leeder (1982) concluded that the higher CMM mortality among immigrants arriving during childhood and adolescence suggested that young people may be especially susceptible to a melanoma-initiating agent, such as sunlight, which is more prevalent in Australia than in their countries of birth.

Holman and Armstrong (1984) examined incident melanoma patterns among Western Australians in a case-control study. The 511 cases (23 percent migrants), were classified according to histologic type. The controls were matched by sex, 5-year birth period, and area of residence from the Australian Commonwealth Electoral Roll or, for 10 cases younger than 18 years, from public school student rolls. Sixty-five percent of all immigrants in the study were born in the U.K. The authors did not, however, provide a numerical breakdown of the places of birth of the cases and controls. As shown in Table 7-3, the odds ratios calculated for each histogenic type increased with increasing duration of residence (0-24, 25-39, 40-59, and 260 years), especially for nodular melanomas (NM) and Hutchinson's melanomic freckle (HMF). The trend of increasing melanoma incidence with increasing duration of residence was statistically significant (P<=0.003) for all melanomas combined and each histogenic type except for unclassified melanoma (UCM).

Holman and Armstrong (1984) also evaluated the CMM risk associated with age at arrival and discovered that age at arrival was a better predictor than duration of residence for risk of all melanomas combined and superficial spreading melanoma (SSM). For NM and HMFM, the variables age at arrival and duration of residences were too highly interrelated to permit separation of their effects. The data on 267 SSM case-control pairs were further analyzed by age at arrival after controlling for ethnicity (i.e., numbers of European, African, and Asian grandparents). The results are presented in Table 7-4. The risk of SSM in immigrants arriving between 0-4 and 5-9 years were somewhat though not significantly greater than that for native-born Australians. The odds ratios were less than one, however, for those immigrants arriving between 10-14 and 15-19 years of age and then generally stabilized around 0.25 for subsequent ages of arrival. The trend in odds ratios by age at arrival was significant (p=0.0001). Holman and Armstrong (1984) concluded that the results for SSM suggested a crucial age at arrival somewhere between 10 and 15 years of age, before which exposure to sunlight in early childhood may play a role in the production of benign nevi. They hypothesized that the benign nevi in turn may act as precursor lesions for SSM.

Holman and Armstrong (1984) also observed an increased proportion of palpable nevi on the arms of controls of English, Celtic, or Australian heritage who were born or arrived in Australia before 10 years of age compared with those who were 10 years or older at arrival. They hypothesized that if the production of "initiated nevus cells" was a step in the pathogenesis of SSM, then the potential to develop SSM would be determined by the number of initiated nevus cells induced in childhood or young adulthood. This, they concluded, could explain the overriding effect of age at arrival versus duration of residence in Australian immigrants with SSM, and the uniformly low rate of SSM in immigrants arriving after 10-14 years of age. They further concluded that it would be difficult to propose a factor other than sun exposure that could account for the lower CMM incidence rate in British migrants compared with native-born Australians, the majority of whom were of British descent.

A recent migrant study (Cooke and Fraser 1985) focused on 893 melanoma cases who died between 1972 and 1980 in New Zealand. The data were obtained from the National Health Statistics Center and, for immigrant cases, were restricted to those with at least 5 years' residence in New Zealand. Mortality rates for the New Zealand-born were calculated using 1976 census data, while for immigrants an unpublished census table of "usually resident" populations was used. Cooke and Fraser (1985) observed that CMM mortality rates were consistently lower for European immigrants than for those born in New Zealand although the number of deaths in some immigrant groups (e.g., the Netherlands) was small. The authors compared mortality rates by age and sex for New Zealand-born cases from 1972 to 1980, for U.K. immigrants from 1972 to 1980, and for CMM cases in England and Wales in 1976. The immigrant mortality rates were intermediate between rates for England and Wales and rates for New Zealanders (except for 15- to 54-year-old female immigrants, with only four CMM deaths from 1972 to 1980). The age-standardized mortality rate for 35- to 64-year-olds was higher for those arriving in New Zealand before 30 years of age (7.1/10[5]; 95% CI 4.6-10.5) than at 30 years or older (2.8/10[5]). Alternatively, the age-standardized mortality rate for 35 to 64-year-olds was higher for those living in New Zealand for at least 20 years (3.9/10[5]) than for those residing in New Zealand for 5 to 19 years (2.9/10[5]). The authors concluded that an early age at migration appeared to be associated with increased risk of CMM death among immigrants, a risk similar to that in their adopted country. The authors postulated that some factor acting in the first few decades of life, possibly patterns of sun exposure, was important in determining CMM risk.

A Hawaiian study (Hinds and Kolonel 1980) provided results which contradicted those from most other studies. The investigators found that among 265 Caucasian CMM cases, age-adjusted incidence rates among immigrants to Hawaii were much greater than rates among Hawaiian-born Caucasians. The study did not include information on country of birth, ethnic background, duration of residence, or age at arrival. Without more detailed data on these variables, the differences in incidence rates cannot be meaningfully explained. The authors indicated, however, that the immigrating Caucasian population may have been more susceptible to melanoma than the primarily Portuguese, native Caucasian population.

FINDINGS

Evidence from the studies reviewed in this chapter supports the following findings:

7.1 Immigrants moving to sunnier climates in which the native CMM incidence rates exceed those of the immigrant's country of origin tend to have lower CMM risks than the native population. These risks increase, however, with increasing duration of residence or earlier age of arrival in the adopted homeland.

7.2 In an Australian study, age at arrival in Australia was more important than duration of residence with respect to the risk of SSM. Arrival before age 10 was associated with a risk near to or greater than the estimated risk of SSM for those born in Australia. Risks decreased in association with age at arrival at 10-14 years relative to those born in Australia; risks stabilized at a significantly lower level for those who arrived at or after age 15.

REFERENCES

Anaise, D., Steinitz, R., and Ben Hur, N. Solar Radiation: A possible etiological factor in malignant melanoma in Israel; A retrospective study (1960-1972). Cancer 42:299-304 (1978).

Cooke, K.R., and Fraser, J. Migration and death from malignant melanoma. Int J Cancer 36:175-178 (1985).

Dobson, A.J., and Leeder, S.R. Mortality from malignant melanoma in Australia: Effects due to country of birth. Int J Epidemiol 11(3):207-211 (1982).

Hinds, M.W., and Kolonel, L.N. Malignant melanoma of the skin in Hawaii, 1960-1977. Cancer 45:811-817 (1980).

Holman, C.D.J., and Armstrong, B.K. Cutaneous malignant melanoma and indicators of total accumulated exposure to the sun: An analysis separating histogenetic types. JNCI 73:75-82 (1984).

Holman, C.D.J., Mulroney, C.D., and Armstrong, B.K. Epidemiology of pre-invasive and invasive malignant melanoma in Western Australia. Br J Cancer 25:317-323 (1980).

Houghton, A.N., and Viola, M.V. Solar radiation and malignant melanoma of the skin. J Am Acad Dermatol 5:477-483 (1981).

Katz, L., Ben-Tuvia, S., and Steinitz, R. Malignant melanoma of the skin in Israel: Effect of migration. In: Trends in Cancer Incidence: Causes and Practical Implications. Magnus, K. (ed). New York:Hemisphere Publishers, Corp. Pp. 419-426. (1982).

Lee, J.A.H. Melanoma and exposure to sunlight. Epidemiologic Reviews 4:110-136 (1982).

Movshovitz, M., and Modan, B. Role of sun exposure in the etiology of malignant melanoma: Epidemiologic inference. J Natl Cancer Inst 51(3):777-779 (1973).