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British Journal of Industrial Medicine 1987;44:278-280 Incidence of cancer among vinyl chloride and polyvinyl chloride workers: further evidence for an association with malignant melanoma S STORETVEDT HELDAAS,1 A A ANDERSEN,2 SLANGArD3 From the Health Department!Research Center,' Norsk Hydro A/S, Porsgrunn Fabrikker. 3900 Porsgrunn, the Cancer Registry of Norwayf Montebello, Oslo 3, and Telemark Sentrahjukelmsf Department of Occupational Medicine, 3900 Porsgrunn, Norway In a previous report1 we presented results of a mor tality study in a cohort of 454 male workers producing vinyl chloride and polyvinyl chloride which gave sup port to the observations from animal studies2 that vinyl chloride (VCM) may act as a multicarcinogcn in man. We report here our finding of two new cases of malignant melanoma of the skin in the extended fol low up period 1980-4 versus 0 3 expected, giving six cases versus H expected overall. Salmon discussed the importance of considering that less specific tumours might also be induced by exposure to VCM, and that high background incidences of such tumours make it difficult to show an increased incidence.3 He found it difficult to dismiss the excess of malignant melanoma in the study population as being the result of confounding factors, owing to the lower back ground incidences and the fact that the confounding variables (race, sunlight exposure) arc more connected with geography than with personal habits, and there fore less likely to vary between control and exposed populations. Salmon also suggested that exposure to ethylene dichloride should be taken into consideration in our study population since it had been used in the process on site.3 and he suggested that our data should be reviewed with exposure to ethylene dichlonde in mind. Since there was an increase in production and in the number of employees during the work period in which members were recruited to the cohort, the observation period was short for some of the members.1 Associations between occupational exposure fac tors and malignant melanoma of the skin have been suggested by some authors. In a study based on a proportionate mortality analysis Thomas and Decoufle found increased mortality of malignant melanoma among white male pharmaceutical production workers.4 Alderson and Rushton found Aecepled 8 July 1986 excess deaths from malignant melanoma among oil refinery workers 3 Beral et a! showed that individuals with exposure to fluorescent lights at work had an increased risk of developing malignant melanoma,6 whereas Rigel et a! found no such association. Wright et al reported exposure to organic chemicals and increased risk of developing malignant mela noma.8 Vagero et a! found that work environments in the telecommunication industry where soldering was practised were associated with excess risk of malig nant melanoma,9 In a register based study where occupational units were classified in terms of the probable amount of soldering work Sorahan et al found no such association.10 Table 1 Broad categories of work indicating exposure levels by follow up period, observed 10 and expected (E) cases of colon cancer t ICO 153), bromhtal cancer (ICD 163/163), and malignant melanoma of the skin (ICD 190) Exposure level Croup ! O Croup 3 OE Croup 3 OE Follow up period 1955-84 ICD 153 514 ICD 162,063 6:5 ICD 190 407 Person-years 6539 0 Follow up period 1Q53--79. ICD 153 3 09 ICD 162/163 4 1 1 ICD 190 3 05 Prrsoti-years 5370 0 Follow up period 19S0-4. ICD 153 205 ICD 162/163 2 OS ICD 190 1 0-2 Person-year* 1169 0 0 05 010 2 03 2362 5 0 0-3 0 0-6 1 02 1910 0 002 0 04 101 452 5 0 02 I 05 00 I 1090 5 002 1 03 00 l 903 0 0 00 002 000 1S7 5 Group I. High VCM twn\l chloride) exposure Group 2' Medium VCM exposure Group 1 Lov- VCM exposure. Total OF. 521 7 40 6I 1 9992 0 3 14 5 26 408 8183-0 207 2/1 4 203 1609 0 278 ASI 00004799 i /m k of ameer among vim I thloride and polyiinyl chloride workers 279 Oh*er\cd O and e\pa led ' E hoc' of tamer (all ole if talon cancer IICD 133/. bronchial cancer /CD M2 !f>3 >. and mnhymini melanoma at die thin IICD 190) in workers employed between iVS0 and 19(i4 stratified h\ iii;r< from first eniploi men! /r.>; Alt i am rr\ Krvt < <mu'nl o e or. a 9 u-19 y :o Tout 5 3 6 14 1? S 7 1 i 13 13 6 in ?i :4 o i : K D 1:1 0E 0E 0 o: _ 3 C6 5 0 t1 ? 19 16 k n to: !63 0 E Of 0 04 _ 3 12 2 5 19 i6 6 3 5 1-7 ICD 190 0E OE 0 1 20 0 2 t 04 50 04 50 6 09 t> 7 Persi>n-ucrs 3110 0 3067-0 :is?5 F364 5 Materials and methods The description of the stud) plant, the population, the estimation of exposure, job classification, and the method of follow up were essential!) the same as in the study conducted in 1979 1 When reviewing data about members of the cohort, however, it could be shown that some of them had been accounted for more than once in the first investigation due to different exposure categorisation. This was not the case for the patients with cancer, but since the study was based on a com parison of observed and expected values from calcu lations on person-vears. the estimated expected values in the first report were slightly too high The study population in our first report consisted of 454 male workers and in the present investigation it was ^^^cd to 430 male workers. Results A review of the updated results is presented in table 1. Nine different exposure categories have been com bined into three groups reflecting high, medium, and low exposure to YCM. Table 1 also presents the observed and expected numbers for those malignant neoplasms that seem to be of interest. For com parison. the follow up periods 1953-54. 1953-79, and 1980-4 are presented separately. The increased inci dence of cancer of the colon, bronchial cancer, and malignant melanoma of the skin--as shown in the previous report1--was confirmed, and was accounted for by the high exposure group. No new cases of liver angiosarcoma appeared in the extended follow up period. Six malignant melanomas of the skin were observed in the whole studv population ver>us H expected (table 1). Two new cases appeared m the extended follow up period versus 0 3 expected In addition we are aware of one ease of incipient malignant mela noma diagnosed in 1977 which was recruited from the medium exposure group. This ease has not been included in the table. The tumours were located as follows: three on the trunk, two in the face-neck area, and one on the foot. The incipient malignant mela- noma was located on the trunk. The mean time between first exposure and the time of diagnosis for the seven cases occurring during the follow up period was 17-4 years (range 2-33). Seven cases of lung can cer were found in the study population versus 4 0 expected and two new cases versus 1 4 expected appeared in the extended follow up period. Six of the seven eases were recruited from the high exposure group (table I). Five eases of colonic cancers were observed versus 2 ! expected. Two new cases versus 0 7 expected occurred in the extended tollow up period. Table 2 presents the results stratified by )ear since first exposure in those workers who were employed between 1950 and 1964 when the level of exposure to VCM must have been high 1 For malignant mela noma there is a difference in the rate ratio between the follow up periods, with highest incidence for the shortest follow up period. For lung cancer, however, there is no apparent difference in the rate ratio between the observation periods. Discussion The excess incidence of malignant melanoma of the skin, lung cancer, and colonic cancer found ir. the prcv'ious study1 was also seen in the present follow up study. The presented results also seem to support (he view that VCM acts as a mulncarcinogen in man. which is in accordance w ith observ 3tions from animal studies.: Salmon suggested that exposure to ethylene dichloridc should be considered as a possible causal chemical in our study population as it had been used in the process on site.3 The cracking of EDC to VCM. however, was introduced in 1967 and discontinued in 1971 and exposure to EDC could be documented m only one of the colonic cancers, but this worker had had only one year of exposure to EDC and VCM and he had also been exposed to asbestos. We discussed the increased nsk of lung cancer and colonic cancer in our first investigation,1 and we have no additional comments. From table 2 it may be deduced that two of the workers in which colonic cancer developed started to work in 1968 and 1969 frSl 00004800 t'jyy m 2S0 respectively This weakened the suggested association to exposure to \'CM, since the exposure to VCM was lower1 and the latent period was short As discussed above there is no evidence that exposure to EDC could explain the findings The extended observation period has confirmed the results from the first investigation, which suggested association between exposure to VCM and malignant melanoma of the skin. The additional cases even seem to strengthen the association between exposure to VCM and the development of malignant melanomas. Only the incipient case w as diagnosed by the company physician Therefore, it seems unlikely that the pres ence of an occupational health service has influenced the results. The incidence of cutaneous malignant melanoma is said to be increasing in all parts of the world where records are kept." The reason for the rising incidence has still not been fully understood. Many authors have concluded that the association between exposure to ultraviolet light (or sun) and the development of malignant melanoma of the skin was complex" 12 or indirect.1' Unlike patients with skin cancers such as squamous and basal cell carcinoma, the patient with melanoma was not an elderly individ ual with a high total lifetime exposure to sun like patients with cancers of the skin such as squamous and basal cell carcinoma 13 Sober and Fitzpatrick discussed genetic and environmental factors and the induction of malignant melanoma 14 Environmental chemicals such as tear gas fx-chloroacetophenone) and polychlorinated biphenyls (PCEk) were suggested as possible causal agents Hilt ct at posed the question as to whether occupational exposure could contribute to the development of malignant melanoma of the skun and suggested that epidemiological studies lim ned to patients with malignant melanoma should be carried out to investigate occupational exposure as a possible risk factor." Occupational exposure factors such as fluorescent light6' and soldering610 have beer, suggested but not confirmed. In view of the small study and the low number of cases of malignant melanoma of the skin the inter pretation of our findings is tentative. The occurrence Sinrenedt Heldmis, Andersen, of two new cases of malignant melanoma of the skm, however, in the extended follow up period seems to strengthen the indicated causality between exposure to VCM and the development of malignant mclar.orr.a of the skin in man Wc thank Patricia Flor for linguistic help and ^nr.e Eide for typing the manuscript. References I Storetvedt Heidaas S. LangJrd S. Andersen Aa Incidence o'" cancer among \m>! chloride and polyvinvl chloride worke'> Br J fad Med 1984.41 25-30 1 MaUoni C. Lefemmc G, Ghberti A. Experimental research n vinyl chloride icirtmogenests (Archives of Research in Ind-'trial Carcinogenicity, vol 2) Prinston Scientific Publishers. NJ I9S4 3 Sdlmon AG Vin>I chloride' the evidence for human carcircgemeuy in different target organs BrJ Ind Med 1985.42 4 Thomas TL, Decoufie P Mortality among workers employed the pharmaceutical mdusttv, A preliminary investigat or J Oaap Med 1979,21 619-23* 5 Alderman M, Rushion L. Mortality patterns in eight LK c\ refineries Ann AT Acad Sa 19S2;381 139-45. 6 Beral V. Evans S. Shaw H. Milton G Malignant melanoma exposure to fluorescent light at work Lancet 1982m 2^-5 77 Rigel DS. Fridman RJ, Levenstan MJ, Greenwald DT Re tionship of fluorescent lights to malignant melanoma an; '.r view J Dewuiffi! Snrg Oncol I9S3.9.83b-8 s Wright WE, Peters JM. Muck TM Organic chemicals and r; nant melanoma Am J Ind Med 1983,4 577-81 99 Vagero D, Ahlbom A, Ohn R. SahUten S Cancer murbd.,_< among workers in the telecommunications wdustrv Br J frJ Med 19*5.42 191-5 10 Sorahan R, Ashton RHR. Waterhouse JAH, PeLcrs D, C Mjlignant melanoma and occupations involving sold?'' r . IRS Sit'd SU Btvihcm 1985.13 S30 11 MacKie RM Cutaneous malignant melanoma, Br \Ud J 1983.287 1568 9 12 Jonsson P', ONson H Stm exposure and malignant melanoma Lakamdnmgen 19S4.22 2249-52. (In Swedish ) 13 Magnus K Habits of sun exposure and risk of malignant ^eii- noma an analysis of incidence rates in Norway l955-i9^~:> cohort, sex. age, and primary tumor site Cancer li* 48-2329-35 14 Sober AJ, Fitzpatrick TB Genetic and environmental fackr ; malignant melanoma in man, Pigment Cell 1979,5 58-94 15 Hilt B, Hddaas SS. Lanyard S Can occupational exposure ccr- tribute to the development of malignant melanoma of the s.:- Scant! J Emiron Health 1983,9 52-3. . *5? fevyv'.xW ASI 00004801