Anne Kricker

The epidemiology of UV induced skin cancer

There is persuasive evidence that each of the three main types of skin cancer, basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma, is caused by sun exposure. The incidence rate of each is higher in fairer skinned, sun-sensitive rather than darker skinned, less sun-sensitive people; risk increases with increasing ambient solar radiation; the highest densities are on the most sun exposed parts of the body and the lowest on the least exposed; and they are associated in individuals with total (mainly SCC), occupational (mainly SCC) and non-occupational or recreational sun exposure (mainly melanoma and BCC) and a history of sunburn and presence of benign sun damage in the skin. That UV radiation specifically causes these skin cancers depends on indirect inferences from the action spectrum of solar radiation for skin cancer from studies in animals and the action spectrum for dipyrimidine dimers and evidence that presumed causative mutations for skin cancer arise most commonly at dipyrimidine sites. Sun protection is essential if skin cancer incidence is to be reduced. The epidemiological data suggest that in implementing sun protection an increase in intermittency of exposure should be avoided, that sun protection will have the greatest impact if achieved as early as possible in life and that it will probably have an impact later in life, especially in those who had high childhood exposure to solar radiation.

Sunlight and cancer

Epidemiologic evidence on the relation between sunlight and cancer is reviewed. Strong evidence implicates sunlight as a cause of skin cancer, although, for melanoma and basal cell carcinoma, the relationship is complex. Both types of cancer are associated more strongly with nonoccupational exposure than with occupational exposure, and the pattern and amount of exposure each appear to be important. Squamous cell carcinoma appears to be related more strongly to total (i.e., both occupational and nonoccupational) exposure to the sun. The evidence that sunlight causes melanoma of the eye is weak. It shows no latitude gradient and the results of case-control studies are conflicting. There is inadequate evidence to suggest that sunlight does or does not cause any other type of cancer.

Personal sun exposure and risk of non Hodgkin lymphoma: A pooled analysis from the Interlymph Consortium

In 2004–2007 4 independent case‐control studies reported evidence that sun exposure might protect against NHL; a fifth, in women only, found increased risks of NHL associated with a range of sun exposure measurements. These 5 studies are the first to examine the association between personal sun exposure and NHL. We report here on the relationship between sun exposure and NHL in a pooled analysis of 10 studies participating in the International Lymphoma Epidemiology Consortium (InterLymph), including the 5 published studies. Ten case‐control studies covering 8,243 cases and 9,697 controls in the USA, Europe and Australia contributed original data for participants of European origin to the pooled analysis. Four kinds of measures of self‐reported personal sun exposure were assessed at interview. A two‐stage estimation method was used in which study‐specific odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for potential confounders including smoking and alcohol use, were obtained from unconditional logistic regression models and combined in random‐effects models to obtain the pooled estimates. Risk of NHL fell significantly with the composite measure of increasing recreational sun exposure, pooled OR = 0.76 (95% CI 0.63–0.91) for the highest exposure category (p for trend 0.01). A downtrend in risk with increasing total sun exposure was not statistically significant. The protective effect of recreational sun exposure was statistically significant at 18–40 years of age and in the 10 years before diagnosis, and for B cell, but not T cell, lymphomas. Increased recreational sun exposure may protect against NHL.

Sun exposure and Skin Cancer

By 1927 for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), and by 1955 for melanoma, the broad grounds for relating sun exposure to skin cancer had been established: that these are more frequent in residents of areas of high ambient solar irradiance, are more frequent in sun-sensitive people, occur mainly on sun-exposed body sites, are more frequent in people with high sun exposure, and are more frequent in people with benign sun-related skin conditions. The past 40 years have added both quantity and quality to the epidemiological evidence and, most recently, provided direct evidence that sun exposure is the cause of mutations in critical tumour suppressor genes in BCC, SCC and melanoma. Complete or more convincing answers are still needed to many questions of detail. They include whether the pattern of sun exposure is really important in, and acts independently of amount of sun exposure in, affecting the risk of melanoma and BCC; what the shape of the relationship between the amount of sun exposure and risk of BCC and melanoma is when the pattern of exposure is held constant; whether there really is a plateau in risk of BCC and melanoma beyond some level of the amount of exposure; whether this exposure-response relationship depends on cutaneous sensitivity to the sun and in what way; whether sunburn makes a specific contribution to the risk of skin cancer independent of the amount of sun exposure; whether sun exposure close to the time of diagnosis of skin cancer contributes anything to the development of the cancer; what the solar radiation action spectrum is for each kind of skin cancer; and whether sunscreens are effective in protecting against skin cancer.

Sun exposure predicts risk of ocular melanoma in Australia

Previous studies examining sun exposure and ocular melanoma have produced inconsistent results. We investigated this association in a population‐based case‐control study in Australia. Cases (n = 290) aged 18–79 years were diagnosed between January 1996 and July 1998. Controls (n = 893) were randomly selected from the electoral rolls and frequency‐matched to cases by age, sex and state. A self‐administered questionnaire and a telephone interview measured sun exposure on weekdays and weekends at 10, 20, 30 and 40 years of age and over the whole of life for specific jobs and recreations. Multivariate logistic regression models of ocular melanoma and sun exposure contained age, sex, region of birth, eye color and measures of ocular and cutaneous sun sensitivity as covariates. Choroid and ciliary body melanoma (n = 246) was positively associated with time outdoors on weekdays and, less persuasively, total time outdoors but not ambient solar irradiance. Odds ratios increased with increasing exposure to OR 1.8 (95% confidence interval 1.1–2.8) for the highest quarter of sun exposure on weekdays up to 40 years of age for men and women together. The strongest positive associations were for total exposure up to 40 years of age, lifetime occupational exposure and total exposure at about 20 years of age in men; all had odds ratios between 2 and 3 in the highest exposure categories. There was inconclusive evidence for an association between sun exposure and iris (n = 25) or conjunctival (n = 19) melanomas. Sun exposure is an independent risk factor for choroidal and ciliary body melanoma in Australia.

Case-control study of sun exposure and squamous cell carcinoma of the skin

We conducted a case‐control study of sun exposure and squamous cell carcinoma (SCC) of the skin within a population‐based, longitudinal study of skin cancer. Cases had histopathologically confirmed SCC. Subjects were interviewed about their lifetime sun exposure, including exposure to the site of the SCC (sites for controls were assigned randomly). Analysis was restricted to 132 cases and 1,031 controls born in Australia and with no ancestors from southern Europe. The total site‐specific exposure was strongly related to risk of SCC; the odds ratio increased to a maximum of 3.3 at 65,000 hr of exposure before falling slightly. Site‐specific exposure during childhood and adolescence was more strongly associated with SCC than exposure during adulthood. An intermittent pattern of weekly sun exposure was not associated with SCC and the odds ratios for hours of exposure on vacation were close to unity. The number of blistering sunburns to the site was positively associated with SCC. Use of sunscreens and hats showed inconsistent effects. Sun exposure, especially during childhood and adolescence, increases the risk of SCC. The pattern of exposure appears to be unimportant, despite the association with sunburn, which may simply be an indicator of the skins sensitivity to sunlight. Int. J. Cancer 77:347–353, 1998.

Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32

To identify susceptibility loci for non-Hodgkin lymphoma subtypes, we conducted a three-stage genome-wide association study. We identified two variants associated with follicular lymphoma at 6p21.32 (rs10484561, combined P = 1.12 × 10−29 and rs7755224, combined P = 2.00 × 10−19; r2 = 1.0), supporting the idea that major histocompatibility complex genetic variation influences follicular lymphoma susceptibility. We also found confirmatory evidence of a previously reported association between chronic lymphocytic leukemia/small lymphocytic lymphoma and rs735665 (combined P = 4.24 × 10−9).

A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention

BACKGROUND Nonmelanoma skin cancers, such as basal-cell carcinoma and squamous-cell carcinoma, are common cancers that are caused principally by ultraviolet (UV) radiation. Nicotinamide (vitamin B3) has been shown to have protective effects against damage caused by UV radiation and to reduce the rate of new premalignant actinic keratoses. METHODS In this phase 3, double-blind, randomized, controlled trial, we randomly assigned, in a 1:1 ratio, 386 participants who had had at least two nonmelanoma skin cancers in the previous 5 years to receive 500 mg of nicotinamide twice daily or placebo for 12 months. Participants were evaluated by dermatologists at 3-month intervals for 18 months. The primary end point was the number of new nonmelanoma skin cancers (i.e., basal-cell carcinomas plus squamous-cell carcinomas) during the 12-month intervention period. Secondary end points included the number of new squamous-cell carcinomas and basal-cell carcinomas and the number of actinic keratoses during the 12-month intervention period, the number of nonmelanoma skin cancers in the 6-month postintervention period, and the safety of nicotinamide. RESULTS At 12 months, the rate of new nonmelanoma skin cancers was lower by 23% (95% confidence interval [CI], 4 to 38) in the nicotinamide group than in the placebo group (P=0.02). Similar differences were found between the nicotinamide group and the placebo group with respect to new basal-cell carcinomas (20% [95% CI, -6 to 39] lower rate with nicotinamide, P=0.12) and new squamous-cell carcinomas (30% [95% CI, 0 to 51] lower rate, P=0.05). The number of actinic keratoses was 11% lower in the nicotinamide group than in the placebo group at 3 months (P=0.01), 14% lower at 6 months (P<0.001), 20% lower at 9 months (P<0.001), and 13% lower at 12 months (P=0.001). No noteworthy between-group differences were found with respect to the number or types of adverse events during the 12-month intervention period, and there was no evidence of benefit after nicotinamide was discontinued. CONCLUSIONS Oral nicotinamide was safe and effective in reducing the rates of new nonmelanoma skin cancers and actinic keratoses in high-risk patients. (Funded by the National Health and Medical Research Council; ONTRAC Australian New Zealand Clinical Trials Registry number, ACTRN12612000625875.).

Demographic characteristics, pigmentary and cutaneous risk factors for squamous cell carcinoma of the skin: A case-control study

We conducted a case‐control study of squamous cell carcinoma of the skin (SCC) in a cohort of people followed from 1987 to 1994. Subjects were residents of Geraldton, Western Australia, who were between 40 and 64 years of age in 1987. On 2 occasions, in 1987 and 1992, dermatologists examined participants for skin cancers. Subjects were also asked on several occasions about skin cancers that they had had treated. Migrants to Australia had reduced risks of SCC. Furthermore, people who migrated to Australia early in life or, equivalently, lived in Australia for a long time had a higher risk than immigrants who arrived later in life or more recently. People who had southern European ancestry had a much lower risk of SCC than other subjects, most of whom were of British or northern European origin. Among Australian‐born subjects of British or northern European ancestry, the skins sensitivity to sunlight was strongly associated with SCC. The pigmentary traits of hair colour, eye colour and skin colour showed weaker associations. The degree of freckling on the arm was strongly predictive of risk. The risk of SCC increased strongly with increasing evidence of cutaneous solar damage and was most strongly associated with the number of solar keratoses. Our results show that sensitivity to sunlight and high levels of exposure to sunlight are important determinants of the risk of SCC. Int. J. Cancer 76:628–634, 1998.© 1998 Wiley‐Liss, Inc.

Epidemiological evidence for a relationship between life events, coping style, and personality factors in the development of breast cancer

OBJECTIVE Review empirical evidence for a relationship between psychosocial factors and breast cancer development. METHODS Standardised quality assessment criteria were utilised to assess the evidence of psychosocial predictors of breast cancer development in the following domains: (a) stressful life events, (b) coping style, (c) social support, and (d) emotional and personality factors. RESULTS Few well-designed studies report any association between life events and breast cancer, the exception being two small studies using the Life Events and Difficulties Schedule (LEDS) reporting an association between severely threatening events and breast cancer risk. Seven studies show anger repression or alexithymia are predictors, the strongest evidence suggesting younger women are at increased risk. There is no evidence that social support, chronic anxiety, or depression affects breast cancer development. With the exception of rationality/anti-emotionality, personality factors do not predict breast cancer risk. CONCLUSION The evidence for a relationship between psychosocial factors and breast cancer is weak. The strongest predictors are emotional repression and severe life events. Future research would benefit from theoretical grounding and greater methodological rigour. Recommendations are given.