RE: Risk of prostate, breast and colorectal cancer after skin cancer diagnosis

We thank Dr. Grant for his interest in our work.1 We cannot make inference on latitude of exposure, specifically, on latitudes south of about 40°. The subjects diagnosed with skin cancer are most likely, than those without skin cancer, to have been heavily exposed to sun in this Swiss population. Exposure may have occurred in the country with mountainous areas, where sun irradiation is stronger than at sea level,2, 3 or abroad. With reference to smoking, according to the Monograph 83 of the International Agency for Research on Cancer,4 there is evidence suggesting the lack of carcinogenicity of tobacco smoking for female breast cancer. There is clear evidence for the risk of neither prostate cancer nor skin cancer. There is some evidence from prospective cohort and case-control studies that the risk of colorectal cancer is increased among tobacco smokers. However, it is not possible to conclude that the association between tobacco smoking and colorectal cancer is causal (abstracted from reference4, pp. 1183–86). It is, therefore, unlikely that smoking has introduced any major bias, confounding, or modifying effect in the results of our study. The evidence from population-based cohort studies like ours1, 5-7 is open to criticism, but is in any case more valid than that of correlation (ecologic) ones often quoted by Dr. Grant in support of his views. Dr. Soerjomataram and Dr. de Vries suggest to provide additional information to address the issue of surveillance bias and stratified or sub-group analysis in our study.1 Although we caution toward inference based on subgroups, we are glad to provide the information requested, when available. With reference to potential surveillance bias, the number of male skin cancer cases in Vaud and Neuchatel, Switzerland were 15,246 when compared with 13,541 in the Dutch study, and that of population years at risk was 109,176. There is no reason to suppose that inclusion—rather than exclusion—of early prostate cancer introduces selection bias. In the mid 1990's, about 10% of men aged 65 or over may have undergone prostate-specific antigen (PSA) testing in Vaud and Neuchatel,8 and this proportion has risen over more recent years, in the absence, however, of any organised screening programme. The standardised incidence ratio (SIR) of prostate cancer was 1.18 (95% confidence interval (CI): 0.93–1.47) in the first, 1.24 (95% CI: 0.97–1.57) in the second, 1.16 (95% CI: 0.88–1.49) in the third year after diagnosis of skin cancer, and 1.13 (95% CI: 1.02–1.25) in subsequent years. Corresponding values were 1.34, 1.06, 0.89, 1.08 for colorectal, and 1.07, 1.20, 1.09, 1.06 for breast cancer. This weighs against the hypothesis of an early reduction in risk, which levels off with time, due to potentially reduced sunshine exposure after skin cancer diagnosis. With reference to strata of sex, the SIR of colorectal cancer were 1.06 (95% CI: 0.94–1.19) in men, and 1.14 (95% CI: 1.00–1.30) in women. The estimates were not significantly heterogeneous across sexes. We have information on stage and grade of prostate cancer only for recent years; thus numbers of subsequent cancers are inadequate now for any inference. Thus, none of the additional or subgroup analyses indicated by Dr. Soerjomataram and Dr. de Vries modify our conclusion that incidence of colorectal, breast, and prostate cancers is not reduced in patients diagnosed with skin cancer. We agree with Dr. Soerjomataram and Dr. de Vries that collaborative studies would help clarify the issue, and provide acceptable statistical power for subgroup analyses. Dr. Robert Tarone, from the International Epidemiology Institute, Rockville, MD, USA, kindly pointed to us that the expected rates in Table I were smaller than those in Table II.1 The correct Table I is, therefore, enclosed below. The first paragraph of the results section consequently reads as follows: “Table 1 gives the numbers of observed and expected cancers of the prostate, breast, and colorectum following basal and squamous cell skin cancers, skin melanomas, and all skin cancers combined. Overall, 680 prostate cancers were observed vs. 593.4 expected (SIR = 1.15; 95% CI: 1.06–1.24), 440 breast cancers were observed vs. 402.3 expected (SIR = 1.09; 95% CI: 0.99–1.20), and 535 colorectal cancers were observed vs. 488.0 expected (SIR = 1.10; 95% CI: 1.01–1.19). We, also, considered the risk of prostate, breast, and colorectal cancers in separate strata of age at diagnosis, location (head and neck vs. other), and time since skin cancer diagnosis, but found no indication of reduced risk in any of the strata considered, most SIRs for prostate, breast, and colorectal cancers being around or slightly above unity. The SIRs of colorectal cancer were 1.06 (95% CI: 0.94–1.19) for men, based on 292 observed vs. 275.4 expected, and 1.14 (95% CI: 1.00–1.30) for women, based on 243 vs. 212.6 expected.” These changes do not modify the inference and conclusions of our work. We apologize, nonetheless, the readers for the correction, and again thank Dr. Tarone for his careful reading and valuable help. Yours sincerely, Fabio Levi, Lalao Randimbison, Van-Cong Te, Manuela Maspoli Conconi, Carlo La Vecchia