Celtic ancestry, HLA phenotype and increased risk of skin cancer

Abstract

Individuals of Celtic ancestry are claimed to be at greater risk of skin cancer than non-Celts, and various positive and negative associations between certain human leucocyte antigen (HLA) phenotypes and the development of skin cancer have been described. The aims of this study were to determine whether any HLA phenotypes are associated either with Celtic or non-Celtic ancestry, or skin type. One thousand and ten members of the Welsh Bone Marrow Donor Registry (WBMDR), whose HLA phenotypes are known, were asked to complete a questionnaire which enquired as to their family origins and their 'Index of Celtic Ancestry' scored out of 12. Three groups were identified: non-Celts (score < 3), Celts (score > 9), and a subset of the Celts--'high scoring' Celts (score > 10). Details of hair and eye colour and skin type were also requested. Skin type and HLA-A, -B, -DR and -DQ frequencies were compared between the three groups (Celts, non-Celts and 'high scoring' Celts), and a random indigenous population of 9196 members of the WBMDR. Seven hundred and thirty-six replies were received (279 male, 457 female, mean age 31 years). One hundred and forty-four Celts, 51 'high scoring' Celts and 170 non-Celts were identified. Forty-six (32%) Celts had skin type I or II compared with 36 (21%) non-Celts (P = 0.039), and 37 (73%) 'high scoring' Celts had skin type I or II (P < 0.0001). However, there were no significant differences between the groups with regard to hair colour, eye colour or number of episodes of painful sunburn. The frequency of HLA-DR4 was 32% in the non-Celtic group, 44% in the Celtic group (not significant), and 53% in the 'high scoring' Celts (P = 0.008). However, the difference was not significant after correction. There were no significant associations between skin type and HLA phenotype. HLA-DR4 is known to be associated with an increased risk of both basal cell carcinoma and malignant melanoma and its increased frequency in Celts may be an independent risk factor for skin cancer in addition to skin type.

Melanocortin 1 receptor genotype, past environmental sun exposure, and risk of multiple sclerosis

“…10,11 ␣MSH is antiinflammatory 17,18 and postulated to be protective against MS onset. 19 An additional issue that must be considered is that human leukocyte antigen (HLA) type varies across racial groups, and HLA DR15 remains the major identified genetic determinant of MS. 20,21 In this report, we investigate the interplay between genotype, phenotype, and environment to further investigate the possible causal nature between low sun exposure and MS.…”

Ancestry reported by white adults with cutaneous melanoma and control subjects in central Alabama

“…This method is identical to that previously validated in a study of the ancestry of hemochromatosis probands [17]; in part, this method was modified from previously reported methods by including only the country of birth of grandparents [6,14,19]. …”

“…Other participants were defined as "non-Celts." We did not use grandparental surnames or maiden names to quantify the degree of Celtic ancestry as did previous investigators [14,19]. …”

“…HLA-DRB1*04 is significantly associated with cutaneous melanoma in white persons in Alabama [9] and Australia [11,12]. In addition, HLA-DRB1*04 was reported positively associated with cutaneous melanoma in white patients who had a high index of Celtic ancestry [14]. …”

Environmental Factors in Nonmelanoma and Melanoma Skin Cancer

“…They reported that very high exposures contribute to the development of atypical nevi. Not only are fair coloration, red hair, the inability to tan, and a family history of melanoma independent risk factors (Whiteman et al, 1997) but ancestry itself may be an independent factor, as it seems to be for Celts (Long et al ., 1998).…”