A risk prediction model for the development of subsequent primary melanoma in a population-based cohort.

BACKGROUND: Guidelines for follow-up of patients with melanoma are based on limited evidence. OBJECTIVES: To guide skin surveillance, we developed a risk prediction model for subsequent primary melanomas, using demographic, phenotypical, histopathological, sun exposure and genomic risk factors. METHODS: Using Cox regression frailty models, we analysed data for 2613 primary melanomas from 1266 patients recruited to the population-based Genes, Environment and Melanoma study in New South Wales, Australia, with a median of 14 years' follow-up via the cancer registry. Discrimination and calibration were assessed. RESULTS: The median time to diagnosis of a subsequent primary melanoma decreased with each new primary melanoma. The final model included 12 risk factors. Harrell's C-statistic was 0·73 [95% confidence interval (CI) 0·68-0·77], 0·65 (95% CI 0·62-0·68) and 0·65 (95% CI 0·61-0·69) for predicting second, third and fourth primary melanomas, respectively. The risk of a subsequent primary melanoma was 4·75 times higher (95% CI 3·87-5·82) for the highest vs. the lowest quintile of the risk score. The mean absolute risk of a subsequent primary melanoma within 5 years was 8·0 ± SD 4.1% after the first primary melanoma, and 46·8 ± 15·0% after the second, but varied substantially by risk score. CONCLUSIONS: The risk of developing a subsequent primary melanoma varies considerably between individuals and is particularly high for those with two or more primary melanomas. The risk prediction model and its associated nomograms enable estimation of the absolute risk of subsequent primary melanoma, on the basis of on an individual's risk factors, and can be used to tailor surveillance intensity, communicate risk and provide patient education. What's already known about this topic? Current guidelines for the frequency and length of follow-up to detect new primary melanomas in patients with one or more previous primary melanomas are based on limited evidence. People with one or more primary melanomas have, on average, a higher risk of developing another primary invasive melanoma, compared with the general population, but an accurate way of estimating individual risk is needed. What does this study add? We provide a comprehensive risk prediction model for subsequent primary melanomas, using data from 1266 participants with melanoma (2613 primary melanomas), over a median 14 years' follow-up. The model includes 12 risk factors comprising demographic, phenotypical, histopathological and genomic factors, and sun exposure. It enables estimation of the absolute risk of subsequent primary melanomas, and can be used to tailor surveillance intensity, communicate individual risk and provide patient education.

Occupational exposure to trichloroethylene and risk of non-Hodgkin lymphoma and its major subtypes: a pooled InterLymph [correction of IinterLlymph] analysis.

OBJECTIVES: We evaluated the association between occupational exposure to trichloroethylene (TCE) and risk of non-Hodgkin lymphoma (NHL) in a pooled analysis of four international case-control studies. METHODS: Overall, the pooled study population included 3788 NHL cases and 4279 controls. Risk of NHL and its major subtypes associated with TCE exposure was calculated with unconditional logistic regression and polytomous regression analysis, adjusting by age, gender and study. RESULTS: Risk of follicular lymphoma (FL), but not NHL overall or other subtypes, increased by probability (p=0.02) and intensity level (p=0.04), and with the combined analysis of four exposure metrics assumed as independent (p=0.004). After restricting the analysis to the most likely exposed study subjects, risk of NHL overall, FL and chronic lymphocytic leukaemia (CLL) were elevated and increased by duration of exposure (p=0.009, p=0.04 and p=0.01, respectively) and with the combined analysis of duration, frequency and intensity of exposure (p=0.004, p=0.015 and p=0.005, respectively). Although based on small numbers of exposed, risk of all the major NHL subtypes, namely diffuse large B-cell lymphoma, FL and CLL, showed increases in risk ranging 2-3.2-fold in the highest category of exposure intensity. No significant heterogeneity in risk was detected by major NHL subtypes or by study. CONCLUSIONS: Our pooled analysis apparently supports the hypothesis of an increase in risk of specific NHL subtypes associated with occupational exposure to TCE.

The AusD Study: a population-based study of the determinants of serum 25-hydroxyvitamin D concentration across a broad latitude range.

Observational studies suggest that people with a high serum 25-hydroxyvitamin D (25(OH)D) concentration may have reduced risk of chronic diseases such as osteoporosis, multiple sclerosis, type 1 diabetes, cardiovascular disease, and some cancers. The AusD Study (A Quantitative Assessment of Solar UV Exposure for Vitamin D Synthesis in Australian Adults) was conducted to clarify the relationships between ultraviolet (UV) radiation exposure, dietary intake of vitamin D, and serum 25(OH)D concentration among Australian adults residing in Townsville (19.3°S), Brisbane (27.5°S), Canberra (35.3°S), and Hobart (42.8°S). Participants aged 18-75 years were recruited from the Australian Electoral Roll between 2009 and 2010. Measurements were made of height, weight, waist:hip ratio, skin, hair, and eye color, blood pressure, and grip strength. Participants completed a questionnaire on sun exposure and vitamin D intake, together with 10 days of personal UV dosimetry and an associated sun-exposure and physical-activity diary that was temporally linked to a blood test for measurement of 25(OH)D concentration. Ambient solar UV radiation was also monitored at all study sites. We collected comprehensive, high-quality data from 1,002 participants (459 males, 543 females) assessed simultaneously across a range of latitudes and through all seasons. Here we describe the scientific and methodological issues considered in designing the AusD Study.

Postmenopausal hormone therapy and non-Hodgkin lymphoma: a pooled analysis of InterLymph case-control studies.

BACKGROUND: Non-Hodgkin lymphoma (NHL) subtypes, diffuse large B-cell (DLBCL) and follicular lymphoma (FL) have different sex ratios and are diagnosed at ages over 60 years; DLBCL is more common in men and diagnosed at older ages than FL, which occurs more among women. This analysis of postmenopausal women examines the relationship between postmenopausal hormone therapy and NHL. DESIGN: Self-reported use of postmenopausal hormone therapy from 2094 postmenopausal women with NHL and 2731 without were pooled across nine case-control studies (1983-2005) from North America, Europe and Japan. Study-specific odds ratios (OR) and 95% confidence intervals (CI) estimated using logistic regression were pooled using random-effects meta-analyses. RESULTS: Postmenopausal women who used hormone therapy were at decreased risk of NHL (pooled OR = 0.79, 95% CI 0.69-0.90). Risks were reduced when the age of starting was 50 years or older. There was no clear trend with number of years of use. Current users were at decreased risk while those stopping over 2 years before diagnosis were not. Having a hysterectomy or not did not affect the risk. Favourable effects were present for DLBCL (pooled OR = 0.66, 95% CI 0.54-0.80) and FL (pooled OR = 0.82, 95% CI 0.66-1.01). CONCLUSION: Postmenopausal hormone therapy, particularly used close to menopause, is associated with a decreased risk of NHL.

Menstrual and reproductive factors, and hormonal contraception use: associations with non-Hodgkin lymphoma in a pooled analysis of InterLymph case-control studies.

BACKGROUND: The two most common forms of non-Hodgkin lymphoma (NHL) exhibit different sex ratios: diffuse large B-cell lymphoma (DLBCL) occurs more frequently in men and follicular lymphoma (FL) more frequently in women. Looking among women alone, this pooled analysis explores the relationship between reproductive histories and these cancers. MATERIALS AND METHODS: Self-reported reproductive histories from 4263 women with NHL and 5971 women without NHL were pooled across 18 case-control studies (1983-2005) from North America, Europe and Japan. Study-specific odd ratios (ORs) and confidence intervals (CIs) were estimated using logistic regression and pooled using random-effects meta-analyses. RESULTS: Associations with reproductive factors were found for FL rather than NHL overall and DLBCL. In particular, the risk of FL decreased with increasing number of pregnancies (pooled OR(trend) = 0.88, 95% CI 0.81-0.96). FL was associated with hormonal contraception (pooled OR = 1.30, 95% CI 1.04-1.63), and risks were increased when use started after the age of 21, was used for <5 years or stopped for >20 years before diagnosis. DLBCL, on the other hand, was not associated with hormonal contraception (pooled OR = 0.87, 95% CI 0.65-1.16). CONCLUSIONS: Hormonal contraception is associated with an increased risk of FL but not of DLBCL or NHL overall.

Occupational exposure to power frequency magnetic fields and risk of non-Hodgkin lymphoma.

OBJECTIVES: To investigate the risk of non-Hodgkin lymphoma (NHL) using a job-exposure matrix (JEM) to assess exposure to occupational magnetic fields at the power frequencies of 50/60 Hz. METHODS: The study population consisted of 694 cases of NHL, first diagnosed between 1 January 2000 and 31 August 2001, and 694 controls from two regions in Australia, matched by age, sex and region of residence. A detailed occupational history was given by each subject. Exposure to power frequency magnetic fields was estimated using a population-based JEM which was specifically developed in the United States to assess occupational magnetic field exposure. The cumulative exposure distribution was divided into quartiles and adjusted odds ratios were calculated using the lowest quartile as the referent group. RESULTS: For the total work history, the odds ratio (OR) for workers in the upper quartile of exposure was 1.48 (95% CI 1.02 to 2.16) compared to the referent (p value for trend was 0.006). When the exposure was lagged by 5 years the OR was 1.59 (95% CI 1.07 to 2.36) (p value for trend was 0.003). Adjusting for other occupational exposures did not significantly alter the results. CONCLUSIONS: These findings provide weak support for the hypothesis that occupational exposure to 50/60 Hz magnetic fields increases the risk of NHL.

Occupational exposure to pesticides and risk of non-Hodgkin's lymphoma.

Pesticide exposure may be a risk factor for non-Hodgkin's lymphoma, but it is not certain which types of pesticides are involved. A population-based case-control study was undertaken in 2000-2001 using detailed methods of assessing occupational pesticide exposure. Cases with incident non-Hodgkin's lymphoma in two Australian states (n = 694) and controls (n = 694) were chosen from Australian electoral rolls. Logistic regression was used to estimate the risks of non-Hodgkin's lymphoma associated with exposure to subgroups of pesticides after adjustment for age, sex, ethnic origin, and residence. Approximately 10% of cases and controls had incurred pesticide exposure. Substantial exposure to any pesticide was associated with a trebling of the risk of non-Hodgkin's lymphoma (odds ratio = 3.09, 95% confidence interval: 1.42, 6.70). Subjects with substantial exposure to organochlorines, organophosphates, and "other pesticides" (all other pesticides excluding herbicides) and herbicides other than phenoxy herbicides had similarly increased risks, although the increase was statistically significant only for "other pesticides." None of the exposure metrics (probability, level, frequency, duration, or years of exposure) were associated with non-Hodgkin's lymphoma. Analyses of the major World Health Organization subtypes of non-Hodgkin's lymphoma suggested a stronger effect for follicular lymphoma. These increases in risk of non-Hodgkin's lymphoma with substantial occupational pesticide exposure are consistent with previous work.

Ductal carcinoma in situ of the breast, a population-based study of epidemiology and pathology.

In a population-based series of 2109 women with ductal carcinoma in situ (DCIS) diagnosed in 1995-2000 in New South Wales, Australia, incidence increased by an average of 5.5% a year, mostly between 1995 and 1996 and in women 50-69 years of age. This increase paralleled the increases in mammographic screening. BreastScreen NSW, an organised mammographic screening programme, detected 65% of all DCIS. High-grade lesions were 54% of all lesions and were more likely to be 2+ cm in diameter (OR=2.12, 95%CI 1.46-3.14) than low-grade lesions. In all, 40% of DCIS in women younger than 40 years was 2+ cm in diameter compared with 21% in women 40 years and older. Young age, high grade, mixed architecture and multifocality were significant and independent predictors of 2+ cm DCIS.

Use of the WHO lymphoma classification in a population-based epidemiological study.

BACKGROUND: Non-Hodgkin's lymphoma (NHL) is pathologically diverse. Epidemiological investigations into its increasing incidence and aetiology require accurate subtype classification. PATIENTS AND METHODS: Available pathology reports of 717 cases aged from 20 to 74 years in an Australian, population-based epidemiological study of NHL were reviewed by one anatomical pathologist to assign a World Health Organization (WHO) classification category. High or low confidence was assigned to the diagnosis of NHL, cell phenotype and WHO category and reasons given for low confidence. RESULTS: The most informative biopsy reports were from open tissue biopsy (79% of cases), tissue core biopsy (8%), cytology (4%) and bone marrow (9%); 8% of cases had inadequate biopsies for diagnostic purposes. Immunohistochemistry or flow cytometry reports were available for 96% of cases, gene rearrangement studies for 6% and cytogenetics for 3%. The reviewer assigned high confidence to the diagnosis of NHL in 93% of cases and also the phenotype in 88%. While a WHO classification could be assigned in 91% of cases, confidence was high in only 57.5%; insufficient immunophenotyping was the commonest reason for low confidence. CONCLUSIONS: Expert pathology review of a population-based sample of NHL can provide a WHO classification category for most cases. A high level of confidence in the classification, however, would require review of diagnostic material and additional phenotyping.

Ocular melanoma is not associated with CDKN2A or MC1R variants--a population-based study.

Germline variants in the melanocortin 1 receptor gene (MC1R) and the p16 gene (CDKN2A) are associated with an increased risk of cutaneous melanoma. The frequency of these germline variants was examined in a population-based, incident series of 62 ocular melanoma cases and ethnicity-matched population controls. In both cases and controls, 59% of individuals carried at least one MC1R variant and there were no significant differences in the frequency of any of the five most common variants of MC1R. We also found no significant differences between cases and controls in the frequency of any of the four most common variants of CDKN2A, and no melanoma case carried a deleterious germline CDKN2A mutation. Our findings argue against an important predisposing effect of the MC1R and CDKN2A genes for ocular melanoma.

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.

Breast conservation, mastectomy and axillary surgery in New South Wales women in 1992 and 1995.

To measure the increase in uptake of BCT in NSW and its determinants, we examined Cancer Registry records of 2020 women with breast cancer in 1992 and 2883 in 1995 linked to records of their surgical treatment in the NSW Inpatient Statistics' Collection. In parallel, we examined trends and determinants in axillary surgery for breast cancer. Breast conservation increased from 39% of breast cancer in 1992 to 45% in 1995, mainly in women with the smallest cancers. In 1995, mastectomy was still most common in women with larger cancers (OR for breast cancers 3+ cm relative to <1 cm = 5.6, 95% CI 2.9-10.7) and cancers that had spread beyond the breast (OR = 2.0, 95% CI 1.4-2.7 relative to localized to the breast). Urban women had fewer mastectomies than rural women. Axillary surgery, common in 1992 (78%) and 1995 (82%), fell steeply with increasing age and more often accompanied mastectomy (93% in 1995) than BCT (67% in 1995). In 1995 the odds for axillary surgery were some two-fold or more higher for all cancers 1 cm or more in diameter compared with those <1.0 cm and highest for 2.0-2.9 cm cancers (OR = 3.3 95% CI 1.7-6.7 relative to <1.0 cm). Regional spread of the cancer at diagnosis was not a strong predictor. In the absence of collection of treatment data by cancer registries, linkage of cancer registry records with hospital inpatient data is an effective alternative for monitoring breast cancer treatment trends.

Eye color and cutaneous nevi predict risk of ocular melanoma in Australia.

Ethnicity, cutaneous nevi and eye color are generally accepted risk factors for melanoma of the eye, although case-control studies have produced conflicting results. We sought to determine the constitutional risk factors for melanomas of the choroid, ciliary body, iris and conjunctiva in Australia. A population-based case-control study was conducted, with case ascertainment from a prospective national incidence survey and randomly selected community controls. Two hundred and ninety cases aged 18-79 years and diagnosed between 1st January 1996 and 31st July 1998 were enrolled with 916 controls frequency matched by age, sex and State or Territory of residence. Risk of choroidal and ciliary body melanoma (n = 246) was increased in people with grey (OR 2.9, 95% CI 1.5-5.5), hazel (OR 2.2, 95% CI 1.4-3.7) and blue eyes (OR 1.7, 95% CI 1.0-2.7) compared with brown eyes. Risk was also increased in those with 4 or more nevi on their back, those unable to tan, and those who squinted when outdoors as a child. Risk was reduced in people born other than in Australia and New Zealand (OR 0.7, 95% CI 0.5-1.0). Non-brown eye color was a risk factor for iris melanoma (n = 25). No risk factors were identified for conjunctival melanoma (n = 19). Eye color is the strongest constitutional predictor of choroidal and ciliary body melanoma, and may indicate a protective effect of melanin density at these sites. An independent association with cutaneous nevi suggests a role for other genetic factors.

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.

An audit of breast cancer pathology reporting in Australia in 1995.

To measure the quality of pathology reporting of breast cancer and establish a baseline against which future changes can be measured, we audited item completeness in breast cancer reports in Australia in 1995 before the release of specific recommendations from the Australian Cancer Network. Tumour type and size were given in reports of invasive breast cancer for 93% of women, 70% had, in addition, grade and clearance of the margins while only 28% had all recommended information. The most complete items in reports were histological type of breast cancer (99.6% of cases), tumour size (94%, 95% confidence interval (CI) 92-95) and margins of excision (87%, 95% CI 85-89). Histological grade (84%, 95% CI 82-86 of cases) and presence or absence of ductal carcinoma in situ (DCIS) (79%, 95% CI 77-81) were less complete and vessel invasion (61%, 95% CI 58-63) and changes in non-neoplastic breast tissue adjacent to the breast cancer (68%, 95% CI 66-71) the least complete. Less than half the reports of DCIS reported on tumour size (49%, 95% CI 42-57), presence or absence of necrosis (41%, 95% CI 34-49) or nuclear grade (39%, 95% CI 31-46). Around 1500 reports were identified as issued by 147 laboratories and 392 pathologists; 69% of pathologists issued fewer than two reports a month in the audit. We concluded that infrequency of reporting may have contributed to incompleteness of reporting. In addition, we found significant variation across Australian states with some indication that reporting was consistently poor in one state. The audit highlighted areas for improvement for breast cancer reporting in Australia. Research evidence suggests that multifaceted strategies are needed to assist practitioners with implementing more uniform reporting standards.

Breast cancer in New South Wales in 1972-1995: tumor size and the impact of mammographic screening.

To examine the use of mammographic screening in women in New South Wales (NSW), we measured uptake of initial mammograms and estimated the proportions of breast cancers that were screen detected. To see if mammographic screening has been associated with reductions in advanced breast cancers and mortality from breast cancer, we analyzed trends in age-specific and age-standardized breast cancer incidence and mortality from 1972 to 1995 and tumor size in 1986, 1989, 1992 and April to September 1995. Between 1984 and the end of 1995, an estimated 72% of NSW women in their 50s and 67% in their 60s had had at least 1 mammogram and, in 1995, an estimated 39% of invasive breast cancers in women in these age groups were detected by mammography. Before 1989, breast cancer incidence increased only slightly (+1.3% annually) but then, from 1990 to 1995, increased more rapidly (+3.1% annually). Between 1986 and 1995, rates of small cancers (< 1 cm) increased steeply by 2.7 times in women 40-49 years of age and 5.6 times in women 50-69 years of age. The incidence of large breast cancers (3+ cm), after little apparent change to 1992, fell by 17% in women 40-49 years of age and 20% in those 50-69 years of age to 1995. Breast cancer mortality increased slightly between 1972 and 1989 (+0.5% annually) but then fell (-2.3% annually) from 1990 to 1995. We concluded that breast cancer rates had been influenced in expected directions by the introduction of mammographic screening in women resident in NSW. We expect that recent falls in incidence of larger breast cancers and breast cancer mortality will become steeper as screening coverage increases in the second half of the 1990s.

Reproducibility of reported measurements of sun exposure in a case-control study.

We examined the reproducibility of the measurement of sun exposure in a cohort study of nonmelanocytic skin cancer in Geraldton, Western Australia. Two analyses were undertaken: a comparison of cutaneous sun damage with sun exposure reported at interview, and an analysis of test-retest reproducibility of reported exposure. Skin cancers and cutaneous indicators of sun damage (cutaneous microtopography and solar elastosis of the neck) were recorded at a survey in 1987. A case-control study was conducted in 1988 in which subjects were interviewed about their lifetime sun exposure. All subjects had European ancestry. A subset of these subjects was reinterviewed using the same interview schedule in 1993. The comparison of reported exposure with skin damage was restricted to 201 cases of basal cell carcinoma and 700 controls, all of whom were born in Australia and had no southern European ancestors. The analysis of test-retest reproducibility included 62 cases with basal cell carcinoma and 162 controls. After adjustment for the skin's sensitivity to sunlight, cutaneous microtopography explained 7% and solar elastosis of the back of the neck explained 13% of the variance in the reported time spent outdoors. The intraclass correlation between time spent outdoors reported in the two interviews was 0.77 [95% confidence interval (CI), 0.71-0.83], whereas for exposure to a specific anatomical site, it was 0.65 (95% CI, 0.55-0.73). The reported site-specific exposure was lower on the second occasion in controls but higher in cases. The hours of exposure on vacations and the proportion of exposure that occurred on nonworking days had poor reproducibility. Furthermore, cases reported a more intermittent pattern of weekly exposure on the first occasion than on the second, whereas the controls showed little difference in their pattern on the two occasions. The weighted kappa statistic for lifetime painful sunburns was 0.53 (95% CI, 0.41-0.66), and for lifetime number of blistering sunburns, it was 0.54 (95% CI, 0.44-0.65). Thus, the reported sun exposure showed only moderate agreement with biological markers of sun damage. Total sun exposure and, to a lesser extent, site-specific exposure showed good agreement on the two occasions. However, indicators of intermittent sun exposure had poor agreement, and sunburn had only fair agreement.

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 skin's sensitivity to sunlight.