NATAP: Caffeine & Skin Cancer-new study

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Subject: NATAP: Caffeine & Skin Cancer-new study Caffeine May Lower Risk of Common Skin Cancer - see full text belowBy Bankhead, Staff Writer, MedPage TodayPublished: July 02, 2012"We thus conducted a prospective analysis to evaluate the association between the intake of caffeine, caffeinated coffee, decaffeinated coffee, and other foods known to be high in caffeine and the risk of melanoma and nonmelanoma skin cancer in the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS)......In this study, we found an inverse association between coffee consumption and the risk of BCC, which is likely due to the

effect of caffeine. No association was found for SCC or melanoma"Relatively modest caffeine consumption was associated with a significantly lower relative risk of basal cell carcinoma (BCC), data from two large cohort studies showed.People who consumed more than three cups of coffee a month had a 17% reduction in the relative risk of BCC versus individuals who drank less than one cup per month.The association pertained to men and women and to sources of caffeine other than coffee.Investigators

found no association between caffeine consumption and squamous-cell carcinoma (SCC) or melanoma, as reported in the July 1 issue of Cancer Research."Given

that nearly one million new cases [of BCC] are diagnosed each year in the U.S., modification in daily dietary factors with even small protective effects may have great public health impact," Jilali Han, PhD, of Harvard and Brigham and Women's Hospital in Boston, and co-authors wrote in conclusion.Skin cancers are the most common malignancy among white people in the U.S. White Americans have an estimated 1 in 5 lifetime risk of developing skin cancer.Laboratory

studies have consistently shown that oral and topical caffeine prevents

SCC in mice exposed to ultraviolet (UV) light, the authors wrote in their introduction. Other preclinical studies have suggested a potential

mechanistic explanation, as topical caffeine has been shown to induce apoptosis in UV-damaged keratinocytes in mice.Observational data have been less convincing, as studies have shown inconsistent associations between caffeine and skin cancer, including melanoma and nonmelanoma. None of these studies distinguished between caffeinated and

decaffeinated coffee or tea, a key piece of evidence that might show whether other components of coffee or tea have anticancer activity.To

address limitations of current information, Han and co-authors reviewed

data from the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). The NHS included 121,700 women ages 30 to 55 at enrollment in 1976. HPFS enrolled 51,529 men ages 40 to 75 when the study began in 1976.NHS participants provided information on caffeine intake on several occasions from 1984 to 2006, as did the HPFS participants from 1986 to 2006.Han and co-authors analyzed data for 112,897 participants from the two studies (72,921 women and 39,976 men). During 24 and 22 years of follow-up in the NHS and HPFS, respectively, 22,786 participants developed BCC, 1,953 developed SCC, and 741 developed melanoma.Using U.S. Department of Agriculture data, Han and co-authors estimated caffeine content 137 mg per cup of caffeinated coffee, 47 mg per cup of tea, 46 mg per 12-oz container of caffeinated soda, and 7 mg per 1-oz serving of chocolate.Investigators

stratified the study participants into quintiles of daily caffeine consumption, which range from 31 to 604 mg in NHS and 8 to 584 mg in the

HPFS. The analysis showed an inverse association between caffeine consumption from all sources combined and the risk of BCC.Comparison

of the highest and lowest quintile of caffeine consumption resulted in a

relative risk of 0.82 for BCC in women and 0.87 in men (P<0.0001 for trend in both groups). The relative risk was 0.84 for men and women combined.Coffee

accounted for 78.5% of all caffeine consumption. A separate comparison of skin cancer risk by coffee consumption produced a relative risk of 0.83 for the highest versus lowest quintile (95% CI 0.77 to 0.87). Investigators found a dose-response relationship between caffeine and BCC risk in women (P<0.0001 for trend) and men (P=0.003 for trend).Caffeine

from sources other than coffee tended to have an inverse association with BCC (0.88 in women, 0.93 in men), although the effect did not achieve statistical significance.The authors noted a number of limitations including the reliance on self-report of BCC without confirmation from histology. Also, they noted that statistical power to calculate any relationship between caffeine and melanoma or SCC was lacking because the number of those cancers in the population was much lower than BCC.Finally, they said they were "not able to rule out

other differences between caffeinated and decaffeinated coffee that could also be etiologically relevant."-------------------------

Increased Caffeine Intake Is Associated with Reduced Risk of Basal Cell Carcinoma of the SkinAbstractStudies in animals suggest that caffeine administration helps prevent squamous cell skin cancer development, but there have

been limited epidemiologic studies on the association between caffeine consumption and skin cancer risk. Using data from the

Nurses' Health Study and the Health Professionals Follow-up Study, we prospectively examined risks of basal cell carcinoma

(BCC, 22,786 cases), squamous cell carcinoma (SCC, 1,953 cases), and melanoma (741 cases) in relation to caffeine intake.

proportional hazard models were used to calculate relative risks (RR) and 95% confidence intervals (CI). The amount of

caffeine intake from all dietary sources was inversely associated with BCC risk. Compared with the lowest quintile, the highest

quintile had the lowest risk (RR, 0.82 in women; 95% CI:,0.77–0.86 and RR, 0.87 in men; 95% CI, 0.81–0.94; Ptrend

< 0.0001 in both). A significant inverse association was also found between caffeinated coffee consumption and BCC risk.

Compared with individuals who consumed caffeinated coffee less than 1 cup per month, women who consumed more than 3 cups/d

had the lowest risk (RR, 0.79; 95% CI, 0.74–0.85; Ptrend < 0.0001) and the RR for men was 0.90 (95% CI, 0.80–1.01; Ptrend

= 0.003). Caffeine from other dietary sources (tea, cola, and chocolate) was also inversely associated with BCC risk. Decaffeinated

coffee consumption was not associated with a similar decrease in BCC risk. In contrast, caffeine intake was not found

to be

inversely associated with risks of SCC or melanoma.

Our findings argue that caffeine intake in men and women is inversely

associated with risk of BCC. Cancer Res; 72(13); 3282–9. ©2012 AACR. IntroductionSkin cancers, broadly divided into basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma, are the most frequently

diagnosed malignant tumors among white people in the United States. One in 5 Americans develops skin cancer in his or her

lifetime (1). An individual's risk of developing skin cancer depends on both constitutional and environmental factors. Constitutional

risk factors include skin phototype, eye and hair color, and tanning ability (2), which represents certain component of genetic susceptibility. UV radiation is an established environmental risk factor

for both melanoma and nonmelanoma skin cancer (3).

Animal studies have consistently shown that oral or topical administration of caffeine inhibits SCC development in mice treated

with UV light (4–8). Oral administration of tea inhibited UV-induced carcinogenesis in mice, whereas decaffeinated tea elicited substantially

less inhibitory activity, which was restored by caffeine (6). One potential mechanism for the inhibitory effect of caffeine is the induction of apoptosis in UV-damaged keratinocytes

(9, 10). Apoptosis is an important pathway for keratinocytes to prevent tumor transformation (11). It was shown that topical caffeine administration to mice after UV-B exposure increased the number of apoptotic keratinocytes

as evaluated by sunburn cell formation and other markers of programmed cell death (12, 13). These findings suggest that caffeine intake might protect against the development of skin cancer in humans.

However, the results of epidemiologic studies about the association between coffee and skin cancer have been far from convincing.

A prospective study from Norway first reported an inverse association between coffee and nonmelanoma skin cancer risk in 1986

(14).

Further studies of this cohort with 108 cases of melanoma reported a significant inverse association between coffee consumption

and melanoma risk in women [relative risk (RR) = 0.4; 95% confidence interval (CI), 0.2–0.8] but not in men (RR, 1.8; 95%

CI, 0.4–3.2; refs. 15, 16). However, a case–control study from Italy did not confirm the inverse association for melanoma (17).

An inverse association for nonmelanoma skin cancer was also found in a cross-sectional analysis of 93,676 Caucasian women,

which reported a 30% lower prevalence of nonmelanoma skin cancer for those drinking 6 cups or more than nondrinkers (18). There were also studies suggesting a protective effect of tea consumption against the risk of skin cancer (19, 20).

However, these prior studies did not distinguish between caffeinated and decaffeinated coffee or tea. Therefore, it was

unknown whether the inverse association was due to caffeine or other components of coffee. We thus conducted a prospective

analysis to evaluate the association between the intake of caffeine, caffeinated coffee, decaffeinated coffee, and other foods

known to be high in caffeine and the risk of melanoma and nonmelanoma skin cancer in the Nurses' Health Study (NHS) and the

Health Professionals Follow-up Study (HPFS). ResultsA total of 112,897 eligible participants were included in the analyses (72,921 female nurses and 39,976 male health professionals).

Characteristics of participants in 1986 were similar among the 5 groups of caffeine intake in both cohorts except for

smoking,

which was correlated with caffeine intake (Table 1).

During 24 years of follow-up in the NHS and 22 years of follow-up in the HPFS, a total of 22,786 participants developed BCC,

1,953 participants developed SCC, and 741 participants developed melanoma. The associations between caffeine intake and the

risks of BCC, SCC, and melanoma are shown in Table 2.

The amount of caffeine intake per day was inversely associated with BCC

risk. Compared with the lowest quintile, the highest

quintile of intake had the lowest risk. The RR was 0.82 in women (95% CI, 0.77–0.86) and was 0.87 in men (95% CI, 0.81–0.94;

Ptrend < 0.0001 in both). The RR was 0.84 (95% CI, 0.80–0.87) for men and women combined by meta-analysis. The restricted cubic

spline curve (Fig. 1)

confirms the inverse association between caffeine intake and the risk of BCC. The consumption of caffeine was not significantly

associated with SCC risk or melanoma risk (Table 2). A significant inverse association was also observed between caffeinated coffee consumption and BCC risk. The dose–response

relationship was significant (Ptrend < 0.0001 in women, and Ptrend

= 0.003 in men). Compared with individuals who consumed caffeinated coffee less than 1 cup per month, women who consumed

more than 3 cups per day had the lowest risk (RR, 0.79; 95% CI, 0.74–0.85), and the RR for men was 0.90 (95% CI, 0.80–1.01).

The RR was 0.83 (95% CI, 0.77–0.87) for men and women combined by meta-analysis. However, decaffeinated coffee consumption

was not associated with a decreased risk of BCC (Table 3).The association between caffeine intake per day (mg, continuous variable) from different sources and the risk of BCC is shown

in Table 4.

Caffeine from coffee, which accounted for 78.5% of total caffeine intake in our study population, was inversely associated

with the risk of BCC in both women (RR for 100 mg/d

= 0.97; 95% CI, 0.97–0.98) and men (RR for 100 mg/d = 0.99; 95% CI, 0.98–0.998).

Caffeine from other dietary sources (tea, 18%; cola, 3%; and chocolate, 0.5%), which accounts for 21.5% of total caffeine

intake, was also inversely associated with BCC risk

with nonsignificant RR comparable with that of caffeine from coffee. The

RR for 100 mg/d was 0.88 (95% CI, 0.75–1.04) in women and 0.93 (95% CI, 0.18–4.84) in men. The consumption of caffeinated coffee or decaffeinated coffee was not significantly associated with risk of SCC (Supplementary

Table S1) or melanoma (Supplementary Table S2).

No significant interactions were found between the susceptibility score (or individual risk factor) and caffeine intake on

the risk of BCC, SCC, or melanoma. The association between caffeine intake and the risk of SCC or melanoma did not vary across

different body sites (data not shown).

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