Nils Jonsson

Risk of cutaneous malignant melanoma in relation to use of sunbeds : further evidence for UV-A carcinogenicity

In a population-based, matched, case–control study from southern Sweden of 571 patients with a first diagnosis of cutaneous malignant melanoma and 913 healthy controls aged 16–80 years, the association between sunbed use and malignant melanoma was evaluated. A total of 250 (44%) cases and 372 (41%) controls reported ever having used sunbeds. A significantly elevated odds ratio for developing malignant melanoma after regular exposure to sunbeds was found, adjusted for hair colour, raised naevi, skin type and number of sunburns (odds ratio (OR) 1.8, 95% confidence interval (CI) 1.2–2.7). A dose–response relationship between total number of sunbed uses and melanoma risk was only found up to the level of 250 times. The OR was higher in individuals younger than age 36 years (adjusted OR 8.1, 95% CI 1.3–49.5 for regular vs never use). The association seemed to be true only for subjects with black/dark brown or light brown hair and among females. Lesions of the extremities showed the strongest association of increased risk with sunbed use. An increased risk was related to commercial exposure and to exposure during the winter. The results substantiate the hypothesis that exposure to sunbeds might increase the risk of developing malignant melanoma.

Is the use of sunscreens a risk factor for malignant melanoma

The relation between use of sunscreens, different host factors and malignant melanoma was investigated in a population-based, matched case–control study of malignant melanoma in the South Swedish Health Care Region, which has the highest risk for melanoma in Sweden, between 1 July 1988 and 30 June 1990. In total, 400 melanoma patients and 640 healthy controls aged 15–75 years answered a comprehensive questionnaire regarding different epidemiologic variables, including questions on use of sunscreens and different constitutional factors. The use of sunscreens was not found to protect against developing malignant melanoma. Instead, an unexpected relation between the use of sunscreens and the risk of developing malignant melanoma was seen (odds ratio (OR) 1.8 for almost always vs never using sunscreens). A tentative dose–response relation was found. Virtually the same ORs were seen in both sexes. Furthermore, persons younger than 50 years had a higher OR than persons older than 50 years. When different melanoma presentation sites were considered, lesions of the trunk were associated with sunscreen use in females (adjusted OR=3.7 for almost always vs never using sunscreens), while lesions of the extremity or head and neck were associated with sunscreen use in males (adjusted OR=3.2 for almost always vs never using sunscreens). Raised naevi on the left arm and freckling were shown to be the major constitutional risk factors (OR=3.9 for more than three naevi vs none and OR=1.4, respectively). The results were essentially unaltered in a histopathologically re-examined material. Further investigations are needed in order to form a basis for melanoma prevention.

Risk of malignant melanoma in relation to drug intake, alcohol, smoking and hormonal factors

In a population-based, matched case-control study from southern Sweden of 400 patients with a first diagnosis of malignant melanoma and 640 healthy control subjects aged 15-75 years, the association between commonly prescribed drugs, alcohol, smoking and malignant melanoma was evaluated. In addition, the relation between reproductive and hormonal factors and melanoma in women was studied. It was found that certain specific types of prescribed drugs, i.e. beta-blockers, hydralazines and benzodiazepines, may increase the risk of melanoma development. However, these associations were diminished, at least for benzodiazepines, after controlling for host factors. As these findings are unconfirmed, and may be due to chance or confounding, further studies are warranted. The risk of malignant melanoma was not influenced by alcohol consumption or smoking habits. Our results do not suggest an association between oral contraceptives and melanoma. Furthermore, reproductive factors were not independent risk factors for melanoma. However, increasing number of live births seemed to be protective (P for trend = 0.01). There is a need for further research to be able to draw firm conclusions on the relation between number of live births and melanoma. The results based on histopathological re-examinations and those based on tumour registry data were essentially the same.

Prognostic factors in invasive cutaneous malignant melanoma: a population-based study and review

A population-based study from Sweden identified 711 patients with cutaneous malignant melanoma diagnosed in 1965, 1975, 1985 and 1989. Prognostic factors were evaluated and a review of the literature was performed. On univariate analysis, thick tumours (> 0.8 mm) (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.6–2.1), increasing Clark level (OR 1.8, 95% CI 1.6–2.0), ulceration (OR 1.8, 95% CI 1.6–2.0), nodular melanoma (OR 1.5, 95% CI 1.3–1.6) and increasing age (continuous variable, P < 0.0001) were associated with a shorter survival. Location on extremities (OR 0.8, 95% CI 0.7–0.9), inflammation (OR 0.8, 95% CI 0.7–0.9) and female gender (OR 0.8, 95% CI 0.8–0.9) were associated with improved survival. On multivariate analysis, thick tumours (> 0.8 mm) (OR 1.5, 95% CI 1.2–1.7) and ulceration (OR 1.4, 95% CI 1.2–1.6) were independently related to a poor prognosis, while location on extremities (OR 0.8, 95% CI 0.7–0.9), inflammation (OR 0.8, 95% CI 0.7–0.9) and female gender (OR 0.8, 95% CI 0.8–1.0) were associated with improved survival. No difference in mean tumour thickness was seen over time, but there was a significant increase in the percentage of thin melanomas (< 0.8 mm) in 1985 (P = 0.01) and 1989 (P = 0.002) compared with 1965. The incidence of melanomas with inflammation increased significantly (P = 0.04), as did age at diagnosis (P = 0.005).

Multiple unrelated clonal chromosome abnormalities in an in situ squamous cell carcinoma of the skin.

We have cytogenetically analyzed short-term cultures from an in situ squamous cell carcinoma of the skin (Bowens disease). The following mosaic tumor karyotype was found: 46,XX, -1, +der(1)(pter----p22::q11----cen----p22:), -9, +der(9)t(1;9)(q11; p24)/46,XX,t(3;6) (q21;p21)/46,XX,t(5;14)(q13;q24),t(7;18)(q32;q11)/46,XX,t(8;11)(p22;q13) /46, XX,t(8;11) (p22;q13),t(15;17) (q13;q24)/46,XX,t(12;15)(q12;p11). None of the rearrangements correspond to previously known cancer-associated abnormalities. Two of the clones are obviously related, and it is reasonable to assume that the t(15;17) developed as an evolutionary change in a cell that already contained t(8;11)(p22;q13). Since five clones without cytogenetic similarities were found in this in situ skin carcinoma, we suggest that the tumor was of polyclonal origin. It is impossible to decide whether all, or indeed any, of the visible abnormalities constitute pathogenetically essential primary changes, or merely represent chromosomal markers of secondary importance in tumorigenesis.

Diverse chromosome abnormalities in squamous cell carcinomas of the skin

Short-term cultures from three invasive squamous cell carcinomas of the skin were cytogenetically analyzed. Clonal chromosome aberrations were found in all tumors. In the first case, two of three abnormal clones were related, and in the second case, two of five clones demonstrated cytogenetic similarities. Both clones detected in case 3 had a structural rearrangement in common. Several nonclonal changes were seen in all three cases in addition to the clonal aberrations. None of the rearrangements detected, clonal or nonclonal, corresponds to any of the consistently cancer-associated aberrations known from other neoplasms. The remarkably diverse karyotypic picture of the three squamous cell carcinomas, in particular the finding of unrelated clones in two of them, hints that these neoplasms may be poly-rather than monoclonal. The lack of a common cytogenetic denominator argues that if chromosomal changes are of pathogenetic importance in this tumor type, a wide variety of apparently dissimilar changes exist that are roughly equal in their capacity to malignantly transform skin epithelium.

Nonrandom karyotypic features in squamous cell carcinomas of the skin.

We report the finding of clonal chromosome abnormalities in 13 short‐term cultured squamous cell carcinomas (SCCs) of the skin. Intratumor heterogeneity, in the form of cytogenetically related (subclones) or unrelated clones, was detected in six tumors. Whereas clones with complex karyotypic changes were found in 6 tumors, clones with simple anomalies were observed in 10 tumors, and sometimes these clones coexisted with highly abnormal clones. Rearrangement of chromosome 8, in the form of isochromosome i(8q) or whole arm translocation, was the most common aberration, found predominantly in complex clones. Another recurrent feature, i.e., the centromeric rearrangement of chromosome 1, as isochromosome i(1q) or i(1p), or whole arm translocations, was always part of a complex karyotype. Homogeneously staining regions were found in two cases, one with a highly complex karyotype and the other with a simple karyotype. In order to obtain an overall karyotypic picture in SCC of the skin, the cytogenetic findings in 10 SCCs reported earlier were reviewed. The chromosomes most commonly affected were, in decreasing order, chromosomes 1, 11, 8, 9, 5, 3, and 7. Chromosomal sites most frequently rearranged were almost all pericentromeric: they were 8q10–q11, 1p10–q12, 5p10–q11, 11p15, and 9p10–q10. Recurrent anomalies were i(1q), i(8q), i(5p), i(1p), i(9p), and i(9q). Among them, only i(8q) and i(9q) might be assumed to be early genetic events, considering the fact that they could occasionally be identified in simple clones. The most frequent losses included part of or the entire chromosomes 2, 4, 9, 11, 14, 18, and 21, arm 8p, and chromosomes X, Y, and 13. Overrepresentation most frequently involved 1q, chromosome 7, and 8q. The characteristic karyotypic pattern observed in skin SCC was in line with the experience in several other carcinomas. Genes Chromosomes Cancer 26:295–303, 1999.

Nonrandom karyotypic features in basal cell carcinomas of the skin

Cytogenetic analysis of short-term cultured 44 basal cell carcinomas (BCC) revealed clonal karyotypic abnormalities in 38 tumors. Relatively complex karyotypes (at least four structural and/or numerical changes per clone) with unbalanced structural as well as numerical aberrations were found in eight (approximately 21%) of the BCC, while the remaining BCC (79%) had simple karyotypes (1 to 3 aberrations per clone). Numerical changes only were found in 16 tumors, 15 BCC displayed both numerical and structural aberrations, and the remaining 7 BCC showed only structural aberrations. Extensive intratumoral heterogeneity, in the form of cytogenetically unrelated clones, was found in 21 tumors, whereas related subclones were present in 10 tumors. In order to obtain an overall karyotypic picture in BCC, the findings of our previously published 25 BCC have been reviewed. Our combined data indicate that BCC are characterized by nonrandom karyotypic patterns. A large subset of BCC is characterized by nonrandom numerical changes, notably, +18, +X, +7, and +9. Structural rearrangements often affect chromosomes 1, 4, 2, 3, 9, 7, 16, and 17. A number of chromosomal bands are frequently involved, including 9q22, 1p32, 1p22, 1q11, 1q21, 2q11, 4q21, 4q31, 1p36, 2q37, 3q13, 7q11, 11p15, 16p13, 16q24, 17q21, and 20q13. When the genomic imbalance is assessed, it has been shown that several chromosome segments are repeatedly involved in losses, namely loss of the distal part of 6q, 13q, 4q, 1q, 8q, and 9p. A correlation analysis between the karyotypic patterns and the clinico-histopathologic parameters has been undertaken in the 44 BCC of the present series. The cytogenetic patterns show a significant correlation with tumor status (P=.025), that is, that cytogenetically more complex tumors are also those clinically the most aggressive. Also, the frequency of cytogenetically unrelated clones is significantly higher in recurrent BCC than that in primary lesions (P=.05). No clear-cut association has been found between the karyotypic patterns and histologic subtypes or tumor sites.

Clinical and histopathological characteristics in relation to aetiological risk factors in cutaneous melanoma: a population-based study.

In this population-based, case-control study from Sweden using data collected from 1988 to 1990, an increased risk of melanoma was associated with the number of sunburns, propensity to freckle, the number of raised naevi and a family history of melanoma. Furthermore, a decreased risk was associated with occupational sun exposure. The purpose of this study was to investigate whether different histopathological features of the melanoma and clinical factors were related to the different aetiological risk factor patterns. All the confirmed primary cutaneous melanomas (n = 366) were included in the study. Both univariate analyses with tests for interaction and multivariate analyses were performed. Patients with melanoma on the trunk and patients with thin melanomas had an excess of close relatives with a history of melanoma (odds ratios [ORs] = 2.7 and 2.3, respectively). A relationship was also seen between melanomas in younger persons and a family history of melanoma (OR = 2.6). The presence of raised naevi on the arm had a tendency to be closer related to melanoma of the nodular type (OR = 4.3) than melanoma of the superficial spreading type (OR = 1.6). Patients with outdoor occupations during summer had a decreased risk of developing melanoma on the extremities. Melanoma diagnosed in patients born before 1939 had an association with sunburns (OR = 1.9) and freckling (OR = 2.0), while melanomas in patients born in 1939 or later were related to a family history of melanoma (OR = 2.2). These results suggest that different histopathological and clinical features of melanoma are associated with different risk factor patterns, which may imply diverging tumour genesis.

Cutaneous malignant melanoma in southern Sweden 1965, 1975, and 1985

There is a worldwide increase in the incidence of cutaneous malignant melanoma (CMM) among whites. In Sweden, a five‐fold increase has been recorded since 1960, although the increase in mortality rate is substantially lower. Tumor thickness is recognized as the most important histologic prognostic factor for primary melanoma. In a previous study, the authors did not find any significant decrease in mean tumor thickness over the period 1965‐1985 in their region. In the current study, prognostic factors for melanoma were evaluated for this time period.