Heterogeneity in Host Risk Factors for Incident Melanoma and Non-Melanoma Skin Cancer in a Cohort of US Women

Background: Melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) are 3 types of skin cancer that have distinct biologic characteristics and prognoses. We evaluated phenotypic differences in the risk of these cancers in US women. Methods: We conducted a prospective study of 113 139 female nurses from 1984 to 2002. Over the 18 years of follow-up, there were 375 cases of melanoma, 495 cases of SCC, and 9423 cases of BCC. Results: Women with melanoma were more likely to have a family history of melanoma (melanoma: RR 1.94, 95% confidence interval [CI] 1.36–2.76; SCC: RR 0.82, 95% CI 0.58–1.37; BCC: RR 1.49, 95% CI 1.38–1.62) and 6 or more moles on the left arm (melanoma: RR 3.66, 95% CI 2.15–6.24; SCC: RR 1.53, 95% CI 0.83–2.79; BCC: RR 1.48, 95% CI 1.28–1.72). Polytomous logistic regression analysis showed that age at diagnosis (P < 0.0001), family history of melanoma (P = 0.016), and number of moles on the left arm (P = 0.007) were significantly different across the 3 cancers. Conclusions: This prospective observational study demonstrated that known phenotypic factors for skin cancer have a differential impact on the risk of melanoma, SCC, and BCC

ABO Blood Group and Incidence of Skin Cancer

Background: Previous studies have examined the association between ABO blood group and the risk of some malignancies. However, no prospective cohort study to date has examined the association between ABO blood group and the risk of skin cancer. Methodology/principal findings: Using two large cohorts in the US, we examined ABO blood type and incidence of skin cancer, including melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC). We followed up study participants (70,650 female nurses and 24,820 male health professionals) on their diagnosis of incident skin cancer from cohort baseline (1976 in women and 1986 in men) until 2006. Study participants reported their blood type in 1996 in both cohorts. During the follow-up, 685 participants developed melanoma, 1,533 developed SCC and 19,860 developed BCC. We used Cox proportional hazards models to calculate the hazard ratios (HR) and 95% confidence intervals (CI) of each type of skin cancer. We observed that non-O blood group (A, AB, and B combined) was significantly associated with a decreased risk of non-melanoma skin cancer overall. Compared to participants with blood group O, participants with non-O blood group had a 14% decreased risk of developing SCC (multivariable HR: 0.86; 95% CI: 0.78, 0.95) and a 4% decreased risk of developing BCC (multivariable HR: 0.96; 95% CI: 0.93, 0.99). The decreased risk of melanoma for non-O blood group was not statistically significant (multivariable HR: 0.91; 95% CI: 0.78, 1.05). Conclusion/significance: In two large independent populations, non-O blood group was associated with a decreased risk of skin cancer. The association was statistically significant for non-melanoma skin cancer. Additional studies are needed to confirm these associations and to define the mechanisms by which ABO blood type or closely linked genetic variants may influence skin cancer risk

Psoriasis and risk of type 2 diabetes among women and men in the United States: a population-based cohort study

Type 2 diabetes (T2D) shares some common risk factors with psoriasis. We evaluated the association between psoriasis and risk of incident T2D among women and men in the United States in a mixed retrospective-prospective cohort study. 184,395 participants were included from an older cohort of women (the Nurses’ Health Study, NHS) (1996–2008), a younger cohort of women (NHS II) (1991–2007) and an older cohort of men (Health Professionals’ Follow-Up Study, HPFS) (1986–2006). During 2,700,958 person-years of follow-up, 9,938 incident T2D cases were confirmed. We found a significantly increased risk of T2D associated with psoriasis only among younger women (NHS II); multivariate-adjusted relative risk (RR) (95% confidence interval (CI)) was 1.25 1.05–1.49). When only including those younger than 60 years during follow-up (NHS and HPFS), we observed a non-significant trend toward increased risk for T2D. In a pooled-analysis of the three cohorts, psoriatics younger than 60 years were at a higher risk of T2D; RR 1.26 (1.08–1.48) for women, and 1.26 (1.08–1.46) for both sexes combined. Further, the risk of T2D was much higher for those developing psoriasis at an early age. In conclusion, we found an association between psoriasis and risk of T2D among individuals younger than 60 years

Association between Cutaneous Nevi and Breast Cancer in the Nurses' Health Study: A Prospective Cohort Study

Background: Cutaneous nevi are suggested to be hormone-related. We hypothesized that the number of cutaneous nevi might be a phenotypic marker of plasma hormone levels and predict subsequent breast cancer risk. Methods and Findings: We followed 74,523 female nurses for 24 y (1986–2010) in the Nurses' Health Study and estimate the relative risk of breast cancer according to the number of cutaneous nevi. We adjusted for the known breast cancer risk factors in the models. During follow-up, a total of 5,483 invasive breast cancer cases were diagnosed. Compared to women with no nevi, women with more cutaneous nevi had higher risks of breast cancer (multivariable-adjusted hazard ratio, 1.04, 95% confidence interval [CI], 0.98–1.10 for 1–5 nevi; 1.15, 95% CI, 1.00–1.31 for 6–14 nevi, and 1.35, 95% CI, 1.04–1.74 for 15 or more nevi; p for continuous trend = 0.003). Over 24 y of follow-up, the absolute risk of developing breast cancer increased from 8.48% for women without cutaneous nevi to 8.82% (95% CI, 8.31%–9.33%) for women with 1–5 nevi, 9.75% (95% CI, 8.48%–11.11%) for women with 6–14 nevi, and 11.4% (95% CI, 8.82%–14.76%) for women with 15 or more nevi. The number of cutaneous nevi was associated with increased risk of breast cancer only among estrogen receptor (ER)–positive tumors (multivariable-adjusted hazard ratio per five nevi, 1.09, 95% CI, 1.02–1.16 for ER+/progesterone receptor [PR]–positive tumors; 1.08, 95% CI, 0.94–1.24 for ER+/PR− tumors; and 0.99, 95% CI, 0.86–1.15 for ER−/PR− tumors). Additionally, we tested plasma hormone levels according to the number of cutaneous nevi among a subgroup of postmenopausal women without postmenopausal hormone use (n = 611). Postmenopausal women with six or more nevi had a 45.5% higher level of free estradiol and a 47.4% higher level of free testosterone compared to those with no nevi (p for trend = 0.001 for both). Among a subgroup of 362 breast cancer cases and 611 matched controls with plasma hormone measurements, the multivariable-adjusted odds ratio for every five nevi attenuated from 1.25 (95% CI, 0.89–1.74) to 1.16 (95% CI, 0.83–1.64) after adjusting for plasma hormone levels. Key limitations in this study are that cutaneous nevi were self-counted in our cohort and that the study was conducted in white individuals, and thus the findings do not necessarily apply to other populations. Conclusions: Our results suggest that the number of cutaneous nevi may reflect plasma hormone levels and predict breast cancer risk independently of previously known factors. Please see later in the article for the Editors' Summar

Prophylactic use of carvedilol to prevent ventricular dysfunction in patients with cancer treated with doxorubicin

Objective: Deterioration in ventricular function is often observed in patients treated with anthracyclines for cancer. There is a paucity of evidence on interventions that might provide cardio-protection. We investigated whether prophylactic use of carvedilol can prevent doxorubicin-induced cardiotoxicity and whether any observed effect is dose related. Methods: A prospective, randomized, double-blind study in patients treated with doxorubicin, comparing placebo (n = 38) with different doses of carvedilol [6.25 mg/day (n = 41), 12.5 mg/day (n = 38) or 25 mg/day (n = 37)]. The primary endpoint was the measured change in left ventricular ejection fraction (LVEF) from baseline to 6 months. Results: LVEF decreased from 62 ± 5% at baseline to 58 ± 7% at 6-months (p = 0.002) in patients assigned to placebo but no statistically significant changes were observed in any of the 3 carvedilol groups. At 6 months, only one of 116 patients (1%) assigned to carvedilol had an LVEF &#60; 50% compared to four of the 38 assigned to placebo (11%), (p = 0.013). No significant differences were noted between carvedilol and placebo in terms of the development of diastolic dysfunction, clinically overt heart failure or death. Conclusions: Carvedilol might prevent deterioration in LVEF in cancer patients treated with doxorubicin. This effect may not be dose related within the studied range

Indoor Tanning and Non-Melanoma Skin Cancer: Systematic Review and Meta-Analysis

Objective: To synthesise the literature on indoor tanning and non-melanoma skin cancer. Design: Systematic review and meta-analysis. Data sources: PubMed (1966 to present), Embase (1974 to present), and Web of Science (1898 to present). Study selection: All articles that reported an original effect statistic for indoor tanning and non-melanoma skin cancer were included. Articles that presented no data, such as review articles and editorials, were excluded, as were articles in languages other than English. Data extraction: Two investigators independently extracted data. Random effects meta-analysis was used to summarise the relative risk of ever use versus never use of indoor tanning. Dose-response effects and exposure to indoor tanning during early life were also examined. The population attributable risk fraction for the United States population was calculated. Results: 12 studies with 9328 cases of non-melanoma skin cancer were included. Among people who reported ever using indoor tanning compared with those who never used indoor tanning, the summary relative risk for squamous cell carcinoma was 1.67 (95% confidence interval 1.29 to 2.17) and that for basal cell carcinoma was 1.29 (1.08 to 1.53). No significant heterogeneity existed between studies. The population attributable risk fraction for the United States was estimated to be 8.2% for squamous cell carcinoma and 3.7% for basal cell carcinoma. This corresponds to more than 170 000 cases of non-melanoma skin cancer each year attributable to indoor tanning. On the basis of data from three studies, use of indoor tanning before age 25 was more strongly associated with both squamous cell carcinoma (relative risk 2.02, 0.70 to 5.86) and basal cell carcinoma (1.40, 1.29 to 1.52). Conclusions: Indoor tanning is associated with a significantly increased risk of both basal and squamous cell skin cancer. The risk is higher with use in early life (<25 years). This modifiable risk factor may account for hundreds of thousands of cases of non-melanoma skin cancer each year in the United States alone and many more worldwide. These findings contribute to the growing body of evidence on the harms of indoor tanning and support public health campaigns and regulation to reduce exposure to this carcinogen

Caffeine Intake, Coffee Consumption, and Risk of Cutaneous Malignant Melanoma

BACKGROUND: Caffeine has been shown to prevent ultraviolet radiation-induced carcinogenesis and to inhibit growth of melanoma cells in experimental studies. We evaluated the association among caffeine intake, coffee consumption, and melanoma risk among three large cohort studies. METHODS: The analysis used data from 89,220 women in the Nurses' Health Study II (1991-2009), 74,666 women in the Nurses' Health Study (1980-2008), and 39,424 men in the Health Professionals Follow-up Study (1986-2008). We used Cox proportional hazards models to estimate the hazard ratios (HR) with 95% confidence intervals (CIs) of melanoma associated with dietary intakes. RESULTS: We documented 2,254 melanoma cases over 4 million person-years of follow-up. After adjustment for other risk factors, higher total caffeine intake was associated with a lower risk of melanoma (≥393 mg/day vs. <60 mg/day: HR = 0.78, 95% CI = 0.64, 0.96; Ptrend = 0.048). The association was more apparent in women (≥393 mg/day vs. <60 mg/day: HR = 0.70, 95% CI = 0.58, 0.85; Ptrend = 0.001) than in men (HR = 0.94, 95% CI = 0.75, 1.2; Ptrend = 0.81), and more apparent for melanomas occurring on body sites with higher continuous sun exposure (head, neck, and extremities; ≥393 mg/day vs. <60 mg/day: HR = 0.71, 95% CI = 0.59, 0.86; Ptrend = 0.001) than for melanomas occurring on body sites with lower continuous sun exposure (trunk including shoulder, back, hip, abdomen, and chest; HR = 0.90, 95% CI = 0.70, 1.2; Ptrend = 0.60). This pattern of association was similar to that for caffeinated coffee consumption, whereas no association was found for decaffeinated coffee consumption and melanoma risk. CONCLUSIONS: Increasing caffeine intake and caffeinated coffee consumption is associated with decreased risk of cutaneous malignant melanomas

Citrus Consumption and Risk of Basal Cell Carcinoma and Squamous Cell Carcinoma of the Skin

Animal experiments have demonstrated the photocarcinogenic properties of furocoumarins, a group of naturally occurring chemicals that are rich in citrus products. We conducted a prospective study for citrus consumption and risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin based on data from 41530 men in the Health Professionals Follow-up Study (1986–2010) and 63759 women in the Nurses’ Health Study (1984–2010) who were free of cancers at baseline. Over 24–26 years of follow-up, we documented 20840 incident BCCs and 3544 incident SCCs. Compared to those who consumed citrus products less than twice per week, the pooled multivariable-adjusted hazard ratios were 1.03 [95% confidence interval (95% CI): 0.99–1.08] for BCC and 1.14 (95% CI: 1.00–1.30) for SCC for those who consumed two to four times per week, 1.06 (95% CI: 1.01–1.11) for BCC and 1.15 (95% CI: 1.02–1.28) for SCC for five to six times per week, 1.11 (95% CI: 1.06–1.16) for BCC and 1.22 (95% CI: 1.08–1.37) for SCC for once to 1.4 times per day and 1.16 (95% CI: 1.09–1.23) for BCC and 1.21 (95% Cl: 1.06–1.38) for SCC for 1.5 times per day or more (P trend = 0.001 for BCC and 0.04 for SCC). In contrast, consumption of non-citrus fruit and juice appeared to be inversely associated with risk of BCC and SCC. Our findings support positive associations between citrus consumption and risk of cutaneous BCC and SCC in two cohorts of men and women, and call for further investigations to better understand the potential photocarcinogenesis associated with dietary intakes

Risk of a Second Primary Cancer after Non-melanoma Skin Cancer in White Men and Women: A Prospective Cohort Study

Background: Previous studies suggest a positive association between history of non-melanoma skin cancer (NMSC) and risk of subsequent cancer at other sites. The purpose of this study is to prospectively examine the risk of primary cancer according to personal history of NMSC. Methods and Findings: In two large US cohorts, the Health Professionals Follow-up Study (HPFS) and the Nurses' Health Study (NHS), we prospectively investigated this association in self-identified white men and women. In the HPFS, we followed 46,237 men from June 1986 to June 2008 (833,496 person-years). In the NHS, we followed 107,339 women from June 1984 to June 2008 (2,116,178 person-years). We documented 29,447 incident cancer cases other than NMSC. Cox proportional hazard models were used to calculate relative risks (RRs) and 95% confidence intervals (CIs). A personal history of NMSC was significantly associated with a higher risk of other primary cancers excluding melanoma in men (RR = 1.11; 95% CI 1.05–1.18), and in women (RR = 1.20; 95% CI 1.15–1.25). Age-standardized absolute risk (AR) was 176 in men and 182 in women per 100,000 person-years. For individual cancer sites, after the Bonferroni correction for multiple comparisons (n = 28), in men, a personal history of NMSC was significantly associated with an increased risk of melanoma (RR = 1.99, AR = 116 per 100,000 person-years). In women, a personal history of NMSC was significantly associated with an increased risk of breast (RR = 1.19, AR = 87 per 100,000 person-years), lung (RR = 1.32, AR = 22 per 100,000 person-years), and melanoma (RR = 2.58, AR = 79 per 100,000 person-years). Conclusion: This prospective study found a modestly increased risk of subsequent malignancies among individuals with a history of NMSC, specifically breast and lung cancer in women and melanoma in both men and women. Please see later in the article for the Editors' Summar