Reproduced, with permission, from:
Longstreth, J. D., ed. 1987. Ultraviolet radiation and melanoma-with a special focus on assessing the risks of stratospheric ozone depletion. Vol. 4, Appendix A of Assessing the risk of trace gases that can modify the stratosphere. Washington, D.C.: U.S. Environmental Protection Agency.
Skin color plays an important role in the determination of ultraviolet radiation (UVR) effects such as erythema or sunburn. Resistance to these effects is conferred by racially determined pigmentation of the skin or by temporary pigmentation from preventive tanning, which increases melanin and thickens the stratum corneum and epidermis in areas of sun-exposed skin. Fair-skinned people require three to five times less UVR to induce erythema than do those with moderately pigmented skin, and up to 30 times less than darkly pigmented people (Parrish et al. 1983). Melanin also plays a protective role in the development of basal and squamous cell carcinomas of the skin. This is seen in the consistent negative association between these effects and skin pigmentation, although the precise mechanisms of protection are not known.
There are also marked differences in cutaneous malignant melanoma (CMM) incidence by skin color, with the disease rates varying by the degree of pigmentation. Epidemiologic evidence from several countries is consistent and shows a clear-cut difference between white and non-white races in the incidence of melanoma. The study of pigmentation differences and melanoma incidence within the Caucasian race provides an opportunity to investigate whether the protective effects of increased pigmentation also moderate the risk of malignant melanoma. Increased pigmentation is known to protect individuals from acute effects on skin exposed to UVR, and results showing similar protective effects against melanoma may provide indirect evidence about the role of sunlight or UVR in the etiology of melanoma.
This chapter reviews studies of racial differences in melanoma incidence from many countries as well as investigations of differences within the Caucasian or white population. The latter studies go beyond the basic white/non-white differences in pigmentation and do not assume that all white skin has the same amount (or lack) of protective melanin. Several epidemiologic measures have been used to define skin differences within Caucasian populations which may alter the susceptibility to melanoma in the presence of a causal factor such as sunlight or UVR exposure. These measures include skin color, hair color, eye color, freckling or a tendency to freckle upon sun exposure, skin reaction to sun (tendency to sunburn, ability to tan), and ethnicity (used to estimate skin color because of the genetic dominance of certain pigmentation characteristics).
RACIAL DIFFERENCES
The International Agency for Research on Cancer (IARC 1976) collected and published data on cancer incidence on five continents, including both age-specific and age-standardized incidence rates from 59 population-based cancer registries in 27 countries. Crombie (1979a) analyzed the IARC data on malignant melanoma using incidence rates standardized to the 1950 world population (Segi 1960) and found a statistically significant three-fold increase in the mean CMM incidence in whites over that of non-whites (Table 10-1). Crombie's analysis assigns populations from the IARC data into white and non-white categories in two ways: seven of the registries are separated by racial group (Crombie treats each of these as an independent population) and the other registries are assigned the white/non-white status presumably by using the information on racial and ethnic background provided to IARC by each registry (IARC 1976). Crombie recognized that the category "non-white" is not completely satisfactory because of the heterogeneous nature of the racial groups included, but the small numbers of melanoma cases for some of the non-white populations made it impossible to analyze them as separate racial entities. For further analysis by race, the registries were treated as samples from the same population and were grouped to obtain age-specific incidence rates for the composite population. The lowest melanoma incidence rates were found among Asian populations, while rates among blacks showed much variation (lower in North America, higher in Africa) (Crombie 1979a). Malignant melanoma in Africans was mostly on the lower limb, frequently on the foot (Crombie 1979a; Kiryabwire et al. 1968; Malik et al. 1974), and may account for the excess incidence in Africans over the Asian groups (see Chapters 5 and 13 for more detail on CMM variation by site).
A study of hospital records in South Africa (Rippey and Rippey 1984) for the years 1959 to 1970 found that CMM was almost six times more common in whites than in blacks. For both sexes combined, the incidence per 100,000 was 6.2 for whites and 1.1 for blacks. By sex, the difference between races remained, but the ratio of white to black was about 13 to 1 for males (5.3/0.4), whereas for females it was only about 4 to 1 (7.0/1.7). These racial differences are consistent with patterns elsewhere in the world, but the incidence rates may not be representative of the true South African rates, particularly for blacks, since there are no reliable population estimates for this racial group.
In 1968, Kiryabwire et al. reported an incidence rate of 1.5/100,000 for melanoma in Uganda based on 152 cases diagnosed during 1963 to 1966. These cases were likely to be black because the author stated in the introduction that CMM is not just "a condition of the white races" and that he would refute this "impression on world-wide statistical analysis."
Another African study reported on a population of mixed races in Sudan (Malik et al. 1974) based on a review of records from two laboratories providing histopathology services for the country. The population was reported to be Arabic, Hamitic, and Semitic, with a variable admixture of Negroid blood. The southern Sudan, where the population is almost exclusively Negroid, had a lower proportion of CMM diagnoses than in other parts of the Sudan. Fifty-two percent of the melanomas occurred in patients from two provinces in the western part of northern Sudan, an area which ethnically is "a mixture of Arabs and Negroids with some preponderance of the latter." CMM incidence rates were not calculated due to factors prevalent in many third world countries, e.g., disparity in availability of medical services and diagnostic facilities in different parts of the country, inadequate health certification, and failure to seek medical attention due to ignorance or shyness in segments of the population.
In each of the three previously mentioned studies in Africa, i.e., those in South Africa (Rippey and Rippey 1984), Uganda (Kiryabwire et al. 1968), and Sudan (Malik et al. 1984), over 60 percent of all malignant melanomas were on the foot, usually on the sole, a less pigmented area of the body in blacks. This factor is discussed in more detail in Chapter 5, but the high occurrence of CMM on the foot in blacks (including American blacks) may indicate the presence of other risk factors in blacks, which may or may not be UV-R- or pigment-related.
Data from the U.S. National Cancer Institute (NCI) on incidence of malignant melanoma by white/non-white racial groups show more striking differences than results from the IARC analyses. The NCI's Surveillance, Epidemiology, and End Results (SEER) Program reported cancer incidence for 1973 to 1983 from 10 cancer registries (5 entire states and 28 counties representing 5 major metropolitan areas within 5 other states) (Sondik et al. 1985). In 1983, the age-adjusted incidence rates (1970 U.S. standard population) were 9.6/100,000 in white males and 0.5/100,000 in black males, with a white:black ratio of 19; in white women, the age-adjusted incidence rate was 8.0/100,000 compared to 0.81/100,000 in black women, with a white:black ratio of 10. Over the period 1974 to 1983, incidence rates remained stable in blacks, while rates increased by 40.5 percent in white males, and by 27.9 percent in white females.
Other U.S. data also show a much higher proportion of malignant melanoma in whites than in other racial groups. A 1980 survey of 614 hospitals studied 4,545 melanoma patients (representing one-third of the total estimated 14,100 cases diagnosed in 1980) and found that 98 percent of the patients were white and less than 1 percent (37 patients) were black (Balch et al. 1984). A retrospective review of melanoma cases at the Duke University Comprehensive Cancer Center during 1972 to 1981 showed similar results. Of the 2,612 patients with melanoma during this period, only 31 (1 percent) were black (Reintgen et al. 1982, 1983). This does not represent a true proportion of black melanoma cases in this geographic area since the Duke Center receives many referral patients from various geographic areas. However, the authors adjusted the melanoma case ratio (83 whites:1 black) by the white-to-black patient ratio at Duke (4:1) and found that the estimated ratio of white-to-black melanoma cases remained high: 20 to 1.
Both New Mexico and Hawaii have particularly high CMM incidence rates in their white populations, showing a significant excess of cases in whites over other races. A study of malignant melanoma from the New Mexico Tumor Registry during 1969 to 1977 showed incidence rates for non-Hispanic whites of 8.7 and 9.0/100,000 in non-Hispanic white males and females, respectively (Pathak et al. 1982). These rates exceeded the total U.S. white rates from comparable years based on data from the Third National Cancer Survey (TNCS) and SEER, and were approximately six times higher than the rates for other ethnic groups in New Mexico (Hispanic, American Indian, and black). The TNCS and SEER results are not fully comparable to the New Mexico results because of the inclusion of Hispanics in the "white" racial group.
Hawaiian Caucasians also have a high incidence of malignant melanoma. For 1968 to 1972, IARC (1976) shows age-adjusted (1950 world standard) incidence of 6.8 per 100,000 for Caucasian males and 5.7 for Caucasian females, while the rates for the remaining population of Hawaii were less than 1.0. Hinds and Kolonel (1980, 1983) analyzed data on malignant melanoma from the Hawaii Tumor Registry and showed an excess of cases in the Caucasian population relative to other Hawaiians as well as a steady increase in the rate of melanoma diagnosed among whites during the study period, 1960 to 1980. Over this time period, 80 percent of the diagnosed malignant melanoma patients were white, even though the white population constituted only 34 percent of the state's population in 1970. Also during this time period, the incidence rates for whites more than tripled (for 1978 to 1980, 24.0 and 19.5/100,00 for males and females, respectively), while the incidence among non-whites remained fairly stable.
A similar situation exists in New Zealand, the country with the second highest incidence of melanoma in the world. Moss (1984) reviewed records from the National Cancer Registry of New Zealand for the years 1963-1981. During this time, the non-Caucasian population of New Zealand (Maoris and Polynesians) had a CMM incidence rate of 2.9/100,000, while the incidence rate in the Caucasian population was 16.9/100,000, a nearly sixfold difference.
Israel has maintained a central cancer registry since 1960 and reports differences in CMM incidence between European-born (including American-born) immigrants and African- or Asian-born immigrants. Movshovitz and Modan (1973) reported that among all foreign-born residents of Israel, CMM incidence was much higher for European-born than for Asian/African-born, based on data from 1961 to 1967. Anaise et al. (1978) analyzed all melanoma cases in the total Israeli Jewish population during 1960 to 1972 and found incidence rates of 3.4 among European-born, 0.44 among Asian-born, and 0.27 among African-born (rates per 100,000). These differences by country of origin may relate more to ethnicity and skin color variation within Caucasians than to actual racial (Caucasian/Negroid) differences, due to the racially heterogeneous population immigrating from Africa.
DIFFERENCES WITHIN CAUCASIANS
While it has been shown that malignant melanoma is more prevalent in the white or Caucasian population than in non-white populations, there are differences in melanoma incidence within the white population which have led researchers to search for more definitive constitutional risk factors than white race. The assumption that all white populations have the same risk of melanoma may lead to errors in the extrapolation of study results to other white populations. For example, Lee and Issenberg (1972) compared CMM incidence and mortality rates from England and Wales with those from Sweden determine whether the different latitudes of two countries (and indirectly, the intensity of solar radiation) might be associated with differences in melanoma as found in earlier studies (e.g., Lancaster 1956). The authors assumed that two white populations with similar latitude might be expected t have similar skin cancer incidence rates if latitude was related to skin cancer, and that a lower latitude would result in an increased incidence rate. In fact, Sweden's rates were higher than those for England and Wales, although Sweden is situated at a higher latitude. This might occur, however if the white populations were not comparable with respect to CMM risk factors, such as tanning ability or sun exposure habits. The authors stated that their results suggested genetic or occupational effects. This genetic contribution to CMM risk may be further investigated by studying skin color differences within the Caucasian population.
Many epidemiologic studies have been conducted to further identify risk factors associated with increased incidence of CMM in Caucasian populations. The following are the variables most frequently investigated for pigmentation differences which may alter susceptibility to CMM within white populations:
Most of the above risk factors are interrelated, requiring controlled analyses to evaluate their independent effects on risk of CMM. Table 10-2 summarizes these measures of skin pigmentation according to the studies which investigated each of them. The study findings associated with these pigmentation variables are discussed in the following sections.
Skin Color
As seen in Table 10-2, skin color was a significant risk factor in all of the studies that considered it. Using all major hospitals in Sydney, Australia, Lancaster and Nelson (1957) age- and sex- matched each of 173 melanoma patients with two control patients (one non-melanoma skin cancer and one non-skin cancer). All patients were of European descent. Skin color was determined "subjectively" by the researchers and classified as fair, medium, or olive. The authors reported a larger proportion of fair-skinned persons in the melanoma and non-melanoma skin cancer groups than in the other cancer controls (77, 72, and 63 percent, respectively).
Gellin et al. (1969), in an age- and sex-matched case-control study of 79 cases and 1,037 controls at the New York University Medical Center, determined that a significantly higher proportion of cases than controls (50 percent vs. 37 percent) had a fair complexion (p<=0.05) based on self-assessment. When analyzed by sex, the greatest difference in the proportion of those with fair complexions was between female cases and controls (61 percent vs. 41 percent, p<=0.05). Although slightly more male cases than controls had fair complexions (36 percent vs. 32 percent), the difference was not statistically significant.
Beral et al. (1983) age-matched 287 white female melanoma cases (18-54 years old) treated in Sydney's Melanoma Clinic during 1975 to 1980 with 574 white female controls and found fair skin to be associated with a twofold increase in relative risk (RR) of CMM (RR=1.9, 95% C.I. 1.38-2.50) as compared to medium or olive skin, after adjusting for hair color. Fair skin was a risk factor independent of hair and eye color, although its importance depended to a certain extent on the associated hair color. For those with red hair, fair skin had only a small additional effect, increasing the risk by 39 percent; for those with blonde hair, the risk was increased by 80 percent; but for those with black or brown hair, the risk was increased by 108 percent.
A case-control study by Elwood et al. (1984) in Western Canada found a relative risk of 2.4 (p<=0.05) for light inner arm skin color as opposed to dark, based on data from 595 melanoma cases and 595 population-based controls (matched on age, sex, and province of residence).
A threefold greater melanoma risk (as indicated by an elevated odds ratio [OR]) was observed for those with the lightest skin relative to those with darkest pigmentation (OR=3.07, 95% C.I. 1.47-6.39), as well as a significant (p<=0.1) linear trend in odds ratios among the four skin pigmentation groups.
In a study based on 499 case-control pairs (matched on sex, 5-year birth period, and area of residence) in Western Australia, Holman and Armstrong (1984b) measured skin color reflectance of the left upper inner arm as an indicator of skin color. For each histogenetic type (HMF, SSM, UCM, or NM), elevated odds ratios were associated with fair skin color of the upper inner arm relative to dark skin.
A case-control study (404 cases, 521 unmatched controls) of CMM patients at Roswell Park Institute (NY) during 1974 to 1980 (Graham et al. 1985) consistently found increased risk with increasing fairness in skin, hair, and eye color. Using self-assessment of fair, medium, and dark, both male and female cases had elevated risks for fair as opposed to those with dark or medium complexions, and there were significantly elevated odds ratios for fair complexions in both males and females (p.<=0.01).
Hair and Eye Color
Six of eight studies found hair and eye color to be significant risk factors for melanoma within Caucasian populations. Regardless of eye color, Beral et al. (1983) found that red hair was associated with a three- or fourfold increase in melanoma risk in women. Individuals with fair skin and red hair had a slightly higher risk (RR=4.4) than those with dark skin and red hair (RR=3.2). All risk analyses were conducted with reference to women with brown or black hair and medium or olive complexions. Blonde hair was associated with a relative risk of 2.7 in fair-skinned women and 1.5 in dark-skinned women. Significantly elevated risks for red hair in childhood (RR=3.0, 95% CI 1.95-4.73) and for blonde hair in childhood (RR=1.6, 95% CI 1.15-2.14) were also noted. Results from analyses of combinations of hair, eye, and skin color show significant relative risks for all women with red or blonde hair or fair skin (Table 10-3). Eye color had no independent effect on risk.
Klepp and Magnus (1979) studied 78 Norwegian CMM cases and 131 unmatched "other" cancer controls in 1974 and 1975 and found no difference between cases and controls with respect to hair and eye color. As mentioned by the authors, these results may be explained by Norway's very homogeneous population of fair-skinned individuals; what may be recorded in other more mixed populations as fair skin or light brown hair may be assessed as "dark" by the predominantly blue-eyed and blonde-haired Norwegians. It is also unlikely that there was sufficient power to detect small differences in a homogeneous population based on the small numbers of cases and controls.
Lew et al. (1983) also found no difference in hair and eye color between 111 CMM cases and 107 controls in Massachusetts. This may have resulted from a bias in the method of control selection. Each patient was to provide two to three friends of the same age (+5 years) and sex for interview; however, 46 cases provided 0 controls, 30 provided 1 each, 28 provided 2 each, and 7 provided 3 each. With no more information on these populations (the authors state that sex and median age were comparable between cases and controls), it is impossible to know what biases may have been introduced.
Lancaster and Nelson (1957), in their study of 173 melanoma cases with age- and sex-matched non-melanoma skin cancer controls and other cancer controls (173 of each), found an excess of red-haired and fair-haired melanoma patients (42 percent) when compared with the non-melanoma skin cancer (36 percent) and other cancer (29 percent) patients. They also found more light-eyed (blue or green-gray) patients among the melanoma and non-melanoma skin cancer patients than among the other cancer controls (61, 66, and 46 percent, respectively).
Gellin et al. (1969) found similar significant differences between their 79 melanoma cases and 1,037 unmatched controls in eye color (55 percent of cases vs. 35 percent of controls had blue or green/gray eyes) and in hair color (26 percent of cases vs. 9 percent of controls had white, blonde, or red hair.
In a Canadian population of 595 white melanoma cases and 595 matched (age, sex, and province of residence) controls, Elwood et al. (1984) found the highest relative risks associated with hair color: 7.1 (95% C.I. 2.6-19.2) for blonde hair in childhood and 3.7 (95% C.I. 1.8-7.7) for red hair as compared with black hair in childhood, adjusting for skin and eye color. Eye color was not independently associated with risk of CMM (adjusting for hair and skin color); this finding is consistent with that of Beral et al. (1983) and Klepp and Magnus (1979). The authors stated that of all the pigmentation variables examined (hair color, skin color of upper inner arm, eye color, and freckles in adolescence), hair color showed the strongest association with an increased risk of malignant melanoma.
Results in an Australian study of 511 melanoma patients and 511 controls matched on sex, 5-year birth period, and area of residence (Holman and Armstrong 1984b) also showed positive results for hair color, while eye color did not contribute to CMM risk after controlling for other pigmentary characteristics. Persons with red hair had nearly twice the risk of those with dark hair (OR=1.89, 95% C.I. 0.99-3.59), while persons with blonde or light brown hair showed intermediate, but significant, levels of risk (OR=1.56 and 1.24, respectively); these findings were of borderline significance. When risk factors were examined by histogenetic type of melanoma, hair color was found to be related to each of the four types (HMFM, SSM, UCM, or NM), while eye color was related to only SSM and NM.
The results of Graham et al. (1985), who used data on 404 melanoma patients and 521 unmatched hospital controls in New York State, indicated there were excesses of CMM for both males and females with blue eyes and fair complexions who had blonde or red hair in childhood. When hair, skin, and eye color were analyzed together, the odds of melanoma increased as the "lightness in tone" increased. Red hair showed significantly elevated odds ratios for males (OR=2.45, p<=0.05), and both red and blonde hair showed positive associations with CMM in females (OR=3.99, p<=0.10, and 2.14, p<=0.01, respectively). Eye color showed similar results; males with blue eyes and females with blue or blue-green/gray eyes all showed significantly elevated odds ratios relative to persons with brown eyes.
Freckling
Of the epidemiologic studies of melanoma reviewed, only four investigated freckling as a risk factor and all found a positive association of CMM incidence with freckling. Although these studies defined this risk factor somewhat differently, their results were consistent regardless of how freckling was ascertained.
Using data on 78 cases and 131 unmatched, non-skin cancer controls, Klepp and Magnus (1979) found significant odds ratios for persons who responded positively to the question: "Do you have freckles, or do you freckle easily?" The risks were particularly high in those aged 20-49 years (RR=3.94 for males and 4.88 for females). In the 50-years-and-older group, only females maintained an elevated risk (RR=2.06).
In a study of CMM in white Australian women (287 cases and ;74 age-matched controls), Beral et al. (1983) found a crude odds ratio of 1.9 for those who reported that they usually freckled after a 30-minute exposure to midday summer sun, relative to those who sometimes or never freckled. After adjustment for hair and skin color, however, the odds ratio associated with freckling was of borderline significance (OR=1.4, 95% C.I. 1.00-1.95).
Elwood et al. (1984b) identified freckles as an important host factor in the development of malignant melanoma, based on analysis of data on 595 age-, sex-, and residence-matched case-control pairs. The risk associated with heavy freckling in childhood and adolescence (RR=2.6) remained significant (RR=2.1, p<=0.001) even after adjustment for other pigmentation factors such as hair, skin and eye color, sun reaction, and ethnic origin.
Holman and Armstrong (1984b) questioned study subjects (511 age-, sex-, and residence-matched case-control pairs) regarding their reactions to chronic sun exposure and found a significantly elevated risk for those who only freckled or never tanned relative to those who tanned deeply (OR=3.53, 95% C.I. 1.82-6.84). After controlling for other pigmentary characteristics (acute reaction to sun, hair, skin and eye color), the risk associated with inability to tan remained significant (OR=2.44, 95% C.I. 1.19-5.02).
Reaction to Sun Exposure
Nine of the studies reviewed assessed reaction to sun exposure. Most studies reported positive associations; however, one (MacKie and Aitchison 1982) reported no significant elevation in risk for melanoma in the sun-sensitive groups, and another (Gellin et al. 1969) reported no association of CMM and sun-sensitivity in males.
In MacKie and Aitchison's study, the skin-types included four categories ranging from "always burns, never tans" (Type I) to "always tans, never burns" (Type IV). No significant differences between CMM patients and controls were found, either as a group or separately by sex. However, this study had a small sample size (113 cases and 113 controls) and was conducted within a relatively homogeneous population (Western Scotland) where 75 percent of the cases and 70 percent of the controls were skin types I or II. These facts should be considered in the interpretation of MacKie and Aitchison's results; the lack of a significant finding does not preclude a potential relationship between severe reaction to sun exposure and CMM.
In a U.S. study of 79 CMM cases and 1,037 unmatched controls, Gellin et al. (1969) found a significant difference only for females. Fifty-six percent of the cases and 38 percent of controls said they sunburned easily; conversely, 9 percent of cases and 25 percent of controls said they tanned easily. Gellin et al. (1969) reported a higher proportion of male controls (33 percent) than male cases (21 percent) who said they sunburn easily and a lower proportion of controls who tan easily (25 percent vs. 41 percent). No explanation was provided for this result based on the analysis of data on 34 male cases and 405 male controls with non-tumor skin conditions, although the result may be due to control selection of only patients with other (non-tumor) skin conditions if those conditions were related to the factors under study, such as reaction to sun exposure and skin type.
In a hospital-based, individually matched case-control study in Sydney, Australia, Lancaster and Nelson (1957) found that 62 percent of 173 melanoma patients reported that they burn easily with sun exposure, as compared with 54 percent of the non-melanoma skin cancer controls and only 36 percent of the other cancer controls.
Responses to the question, "How much sun do you tolerate?" in a Norwegian case-control study of CMM (78 cases and 131 unmatched controls) showed elevated risks for those who answered "very little" or "not very much" versus those who replied "quite a lot" or "very much" in three of the four age-sex groups (Klepp and Magnus 1979). Relative risks for cases were 6.08 for males 20-49 years, 2.42 for females 20-49 years, and 2.00 for females 50 years and over. Only males 50 and over did not have an increased risk associated with low sun tolerance.
Beral et al. (1983) found a slightly elevated but significant relative risk for cases (RR=1.4) who reported "blistering or peeling" after a 30-minute exposure to midday summer sun with no tan versus those reporting milder reactions. After adjustment for skin and hair color, however, the relative risk for this factor was not significant (RR=1.1).
Results from Lew et al. (1983), based on data from 111 melanoma cases and 107 unmatched controls, should be interpreted with caution due to the potential biases from their method of control selection described earlier; their findings, however, are in agreement with results from several other studies--the risk of melanoma was significantly increased among those who had difficulty tanning as an adolescent relative to those who did not. Elwood et al.'s study in Canada (1984) also showed a significant risk (RR=2.3) for those who sunburned and rarely tanned. The risk remained significantly elevated even after adjustment for other significant pigmentation characteristics such as skin and hair color, freckling, and ethnicity (RR=1.7, p<=0.01).
Holman and Armstrong (1984b) separated burning and tanning into acute (blister) and chronic (freckle, no tan) reactions to sunlight and found these two sun-sensitive reactions to be the most significant of the pigmentary risk factors for melanoma in their Australian case-control study (511 matched pairs), even after adjustment for hair, skin, and eye color. Burning and tanning were also analyzed separately by Graham et al. (1985), who showed a twofold significant odds for those who burned or freckled versus those who did not (OR=1.97 for males, 2.02 for females), and a twofold risk (OR=1.95) for females who answered "no" to tanning versus those who responded affirmatively (for males, the increased risk of 1.65 was not statistically significant).
Hereditary Differences
Ethnic background within the Caucasian population has a major role in skin pigmentation and, as such, has been analyzed to identify the presence of a relationship with melanoma incidence. Some early studies analyzed ethnicity using descriptive techniques on incidence data, finding lower rates of CMM for ethnic groups having darker skin tones than other Caucasian ethnic groups, e.g., Spanish or Portuguese.
IARC (1976) published melanoma incidence rates from five continents. These include data on populations from New Mexico (1969-1972) and El Paso, Texas (1968 - 1971), separated into Spanish-origin whites and other whites. The following age-standardized (1950 world population) CMM incidence rates were considerably higher for non-Spanish whites than for Spanish whites in each area:
MacDonald (1976) found similar results when she analyzed 23 years of melanoma incidence data from six major regions in Texas (56 counties). Of the 2,328 cases of melanoma, 91 percent occurred among non-Spanish whites, and only 8 percent among whites with Spanish surnames.
In Hawaii, a state with very high CMM incidence in whites, Hinds and Kolonel (1983) attempted to examine differences in melanoma between the non-Portuguese white and Portuguese white sectors of the population using 1960-1980 data from the Hawaii Tumor Registry. An estimated 10 percent of Hawaiian whites were of Portuguese ancestry, but no exact population figures were available. Analysis of proportional cancer incidence during the study period showed that melanoma accounted for only 0.5 percent of all cancer cases in Portuguese men and 0.2 percent in Portuguese women. In contrast, CMM accounted for 4.7 percent of cancer cases in non-Portuguese white men and 3.1 percent in non-Portuguese white women.
In a hospital interview study of total skin cancers in Sydney, Australia, Land-Brown et al. (1971) used surnames and interview questions to identify ethnic background (Irish as well as Scottish and Welsh Celtic names). The study compared proportions of persons half or more Celtic (Irish, Scottish, and Welsh) between different hospital populations. The melanoma and other skin cancer groups each showed a higher proportion of persons with Celtic heritage than those groups without skin cancer. A random sample of 2,607 names drawn from the Sydney telephone directory resulted in only 26 percent Celtic names, a proportion similar to that in the non-skin cancer hospital groups. In summary, this showed that Celtic heritage was associated with higher proportions of patients diagnosed with basal and squamous cell carcinomas and malignant melanomas than patients hospitalized for reasons other than skin cancer.
Three recent case-control studies (Canada, Western Australia, and New York State) found that ethnicity was a significant risk factor for CMM. In Canada, Elwood et al. (1984) showed a significantly low risk (OR=0.5) among study subjects from Eastern or Southern European background compared with those of English origin. This odds ratio remained significant (p<=0.05) even after adjustment for other risk factors such as pigmentation characteristics and freckling. Likewise, Holman and Armstrong (1984b) found that having two or more Southern European grandparents resulted in a significantly lower risk of melanoma. When the analysis was done controlling for age at arrival in Australia and for pigmentary characteristics, the strength of this protective effect was reduced to a barely significant level. Graham et al. (1985) found a significantly increased risk only for females (OR=2.26, 95% C.I. 1.5-3.5) with an ethnic derivation from Northern European countries (Scandinavia, Poland, Germany, France, British Isles) when compared to women from other ethnic backgrounds.
FINDINGS
The findings presented below are based on the review of epidemiologic studies in this chapter:
7.1 Epidemiologic studies have shown that Caucasian populations have much higher rates of CMM incidence and mortality than black populations. Based on 1983 SEER data, white:black ratios were 19:1 and 8:1 in males and females, respectively.7.2 Differences in CMM incidence and mortality have also been observed between Caucasians and other races. For example, whites in New Zealand experience much higher incidence rates than new Zealand Maoris and Polynesians. Likewise, American Indians experience much lower rates of CMM than American whites.
7.3 Within the Caucasian race, differences in rates of CMM occur according to country of origin. CMM incidence rates for Hispanic whites in New Mexico, for example, are much lower than those for non-Hispanic whites; individuals from the Mediterranean countries in southern Europe tend to have lower rates than Caucasians from northern Europe; individuals of Celtic origin in Australia tend to have higher rates than non-Celtic individuals. Variation in the incidence of CMM within the Caucasian race is commonly thought to be a function of variation in genetically-determined pigmentary traits across ethnic groups.
7.4 Numerous epidemiologic studies have focused on identification of important pigmentary characteristics in the etiology of CMM. The following associations were identified in this chapter:
a) Skin color--fair complexions relative to dark complexions were associated with elevated risks of CMM in all studies reviewed.b) Hair and eye color--red and blonde hair in childhood relative to dark hair were associated with increased risk of CMM in most studies. Blue eyes were an independent risk factor in only one of four well-controlled epidemiologic studies; however, this could be due to the homogeneous nature of most of the study populations.
c) Freckling--those who freckled readily were at consistently elevated CMM risk relative to other individuals.
d) Reaction to sun exposure--individuals who usually burned and were unable to tan were at significantly higher risk of CMM than those who tanned well in most studies reviewed.
7.5 Over the period 1974-1983, incidence rates remained stable in blacks while rates increased by 40.5 percent in white males and 27.9 percent in white females in the U.S.
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).
Balch, C.M., Karakousis, C., Natarajan, N., et al. Management of cutaneous melanoma in the United States. Surg Gynecol Obstet 158:311-318 (1984).
Beral, V., Evans, S., Shaw, H., and Milton, G. Cutaneous factors related to the risk of malignant melanoma. Br J Dermatol 109:165-172 (1983).
Crombie, I.K. Racial differences in melanoma incidence. Br J Cancer 40:185-193 (1979a).
Crombie, I.K. Variation of melanoma incidence with latitude in North America and Europe. Br J Cancer 40:774-781 (1979b).
Elwood, J.M., Gallagher, R.P., Hill, G.B., Spinelli, J.J., Pearson, J.C.G., and Threlfall, W. Pigmentation and skin reaction to sun as risk factors for cutaneous melanoma: Western Canada melanoma study. Br Med J 288:99-102 (1984).
Gange, R.W. and Parrish, J.A. Acute effects of ultraviolet radiation upon the skin. In: Photoimmunology, Parrish, J.A., Kripke, M.L., Morison, W.L. (eds.) New York: Plenum Medical Book Company p. 82 (1983).
Gellin, G.A., Kopf, A.W., and Garfinkel, L. Malignant melanoma: A controlled study of possibly associated factors. Arch Dermol 99:43-48 (1969).
Graham, S., Marshall, J., Haughey, B., Stoll, H., Zielezny, M., and West, D. An inquiry into the epidemiology of melanoma. Am J Epidemiol 122(4): 606-619 (1985).
Hinds, M.W., Kolonel, L.N. Malignant melanoma of the skin in Hawaii, 1960-1977. Cancer 45:811-817 (1980).
Hinds, M.W., and Kolonel, L.N. Cutaneous malignant melanoma in Hawaii - An update. West J Med 138:50-54 (1983).
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 (1984a).
Holman, C.D.J., and Armstrong, B.K. Pigmentary traits, ethnic origin, benign nevi, and family history as risk factors for cutaneous malignant melanoma. JNCI 72:257-266 (1984b).
IARC. Comparison Between Registries Age-Standardized Rates. Chapter 9 in Waterhouse, J., Muir, C., Correa, P. and Powell, J. (eds). Cancer Incidence in Five Continents, Volume III. IARC Scientific Publications, Lyon. pp. 453-543 (1976).
Kiryabwire J.W., Lewis, M.G. Ziegler, J.L., and Loefler, I. Malignant melanoma in Uganda. East Afr Med J 45:498-507 (1968).
Klepp, O., and Magnus, K. Some environmental and bodily characteristics of melanoma patients. A case-control study. Int J Cancer 23:482-486 (1979).
Lancaster, H.O. Some geographical aspects of the mortality from melanoma in Europeans. Med J Aust 1: 1082-1087 (1956).
Lancaster, H.O., and Nelson, J. Sunlight as a cause of melanoma: A clinical survey. The Med J Aust, 6:452-456 (1957).
Lane-Brown, M.M., Sharpe, C.A.B., MacMillan, D.S., and McGovern, V.J. Genetic predisposition to melanoma and other skin cancers in Australians. Med J Aust, April 17:852-853 (1971).
Lee, J.A.H., and Issenberg, H.J. A comparison between England and Wales and Sweden in the incidence and mortality of malignant skin tumors. Br J Cancer 26:59-66 (1972).
Lew, R.A., Sober, A.J., Cook, N., Marvell, R., and Fitzpatrick, T.B. Sun exposure habits in patients with cutaneous melanoma: A case control study. J Dermatol Surg Oncol 9:981-986 (1983).
MacDonald, E.J. Incidence and epidemiology of melanoma in Texas. In: Neoplasms and Malignant Melanoma. Chicago: Year Book Medical Publishers. Inc. pp 279-292 (1976).
MacKie, R.M., and Aitchison, T. Severe sunburn and subsequent risk of primary cutaneous malignant melanoma in Scotland. Br J Cancer 46:955-960 (1982).
Malik, M.O., Hidaytalla, A., Daoud, E.H., and El Hassan, A.M. Superficial cancer in the Sudan: A study of 1225 primary malignant superficial tumors. Br J Cancer 30:355-364 (1974).
Moss, A.L.H. Malignant melanoma in Maoris and Polynesians in New Zealand. Br J Plast Surg 37:73-75 (1984).
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).
National Cancer Institute (NCI). Third National Cancer Survey, 1969-1971: Incidence Data. NCI Monograph 41. Bethesda, Maryland (1975).
National Cancer Institute (NCI). Surveillance Epidemiology and End Results (SEER): Incidence and Mortality Data 1973-1977. NCI Monograph 57, NIH Publ. No. 81-2330. Bethesda, Maryland. (June 1981).
Parrish, J.A., Jaenicke, K.F., and Anderson, R.R. Erythema and melanogenesis action spectra of normal human skin. Photochem Photobiol 36:187-191 (1982).
Pathak, D.R., Samet, J.M., Howard, C.A., and Key, C.R. Malignant melanoma of the skin in New Mexico 1969-1977. Cancer 50:1440-46 (1982).
Reintgen, D.S., McCarty, K.M., Cox, E., and Seigler, H.F. Malignant melanoma in Black American and White American populations: A comparative review. JAMA 248(15): 1856-1859 (1982).
Reintgen, D.S., McCarty, K.S., Cox, E., and Seigler, H.F. Malignant melanoma in the American Black. Curr Surg, May-June:215-217 (1983).
Rippey, J.J., and Rippey, E. Epidemiology of malignant melanoma of the skin in South Africa. SA Med J 65:595-598 (1984).
Sondik, E., Young, J.L., Horn, J.W., and Ries, L.A.G., 1985 Annual Cancer Statistics Review. National Cancer Institute (NCI) (1985).
Segi, M. Cancer Mortality for Selected Sites in 24 Countries (1950-1957). Department of Public Health, Tokohu University School of Medicine, Sendai Japan (1960).
