Coffee,tea and melanoma risk: findings from the European Prospective Investigation into Cancer and Nutrition

In vitro and animal studies suggest that bioactive constituents of coffee and tea may have anticarcinogenic effects against cutaneous melanoma; however, epidemiological evidence is limited to date. We examined the relationships between coffee (total, caffeinated or decaffeinated) and tea consumption and risk of melanoma in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a multicentre prospective study that enrolled over 500,000 participants aged 25–70 years from ten European countries in 1992–2000. Information on coffee and tea drinking was collected at baseline using validated country‐specific dietary questionnaires. We used adjusted Cox proportional hazards regression models to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for the associations between coffee and tea consumption and melanoma risk. Overall, 2,712 melanoma cases were identified during a median follow‐up of 14.9 years among 476,160 study participants. Consumption of caffeinated coffee was inversely associated with melanoma risk among men (HR for highest quartile of consumption vs. non‐consumers 0.31, 95% CI 0.14–0.69) but not among women (HR 0.96, 95% CI 0.62–1.47). There were no statistically significant associations between consumption of decaffeinated coffee or tea and the risk of melanoma among both men and women. The consumption of caffeinated coffee was inversely associated with melanoma risk among men in this large cohort study. Further investigations are warranted to confirm our findings and clarify the possible role of caffeine and other coffee compounds in reducing the risk of melanoma.     

Prospective evaluation of trans-fatty acid intake and colorectal cancer risk in the Iowa Women's Health Study

Concerns regarding the safety of dietary trans-fatty acids (tFAs) have generated recent public interest, scientific discussion and legislative action. Although most widely recognized as a risk factor for cardiovascular disease, associations between tFA intake and incident cancer have also been proposed. With respect to colorectal cancer (CRC), existing observational data remain limited and inconclusive. Therefore, we conducted a prospective evaluation of tFA intake and CRC risk, overall and by anatomic subsite, among participants in the Iowa Women's Health Study (IWHS), a population-based cohort of older women (ages 55-69 years at enrollment). Exposure data were collected at baseline using a semiquantitative food-frequency questionnaire. Incident CRC cases were identified through annual linkage to the Iowa Cancer Registry. CRC risks were estimated using Cox proportional hazards regression models. In total, 35,216 women met our inclusion criteria and 1,229 CRC cases (631 proximal, 571 distal, 27 site not specified) were observed through 18 years of follow-up. Adjusting for age and total energy consumption, tFA intake in the 4th versus 1st quartile was not significantly associated with overall CRC risk [relative risk (RR) = 1.12; 95% confidence interval (CI) = 0.96-1.32]. Similarly, risk estimates based on proximal (RR = 1.09; 95% CI = 0.87-1.37) and distal (RR = 1.18; 95% CI = 0.93-1.49) CRC subsites did not differ from unity. Multivariable adjustment yielded slightly attenuated risk estimates, but the observed associations were not meaningfully altered. Given these findings, tFA intake does not appear to be a major CRC risk factor, at least among older women.     

Contraceptive methods and ovarian cancer risk among Chinese women: A report from the Shanghai Women's Health Study

Oral contraceptive use is associated with reduced ovarian cancer risk; however, associations with other contraceptive methods, such as intrauterine device (IUD) and tubal ligation, are less clear. Women in China differ from western women in regard to mechanisms and duration of use of contraception. This study was undertaken to evaluate associations between contraceptive methods and ovarian cancer risk using data from the prospective Shanghai Women's Health Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression. A total of 174 epithelial ovarian cancer cases were found to occur among 70,259 women who were followed‐up for a total of 888,258 person‐years. The majority of women had ever used any contraception (77.0%), including IUD (55.6%), oral contraceptive (20.4%), tubal ligation (14.7%) or contraceptive shots (2.6%). Ever use of any contraception was associated with a nonsignificant reduction in ovarian cancer risk (HR: 0.86, 95% CI: 0.60–1.24). Longer duration of IUD use was associated with lower ovarian cancer risk (p‐value for trend = 0.04). Compared with never users, women with durations of IUD use longer than the median (20 years) were 38% less likely to develop ovarian cancer (HR: 0.62, 95% CI: 0.40–0.97). Based on the high prevalence and long duration of IUD use among Chinese women, we estimate a preventive fraction of 9.3%, corresponding to approximately 16 ovarian cancer cases. High prevalence of long‐term IUD use may, therefore, contribute to the low incidence of ovarian cancer observed in China.     

Exogenous hormone use and cutaneous melanoma risk in women: The European Prospective Investigation into Cancer and Nutrition

Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country-specific self-administered questionnaires. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 1992–2015, 1,696 melanoma cases were identified among 334,483 women, whereof 770 cases among 134,758 postmenopausal women. There was a positive, borderline-significant association between OC use and melanoma risk (HR = 1.12, 95% CI = 1.00–1.26), with no detected heterogeneity across countries (p_homogeneity = 0.42). This risk increased linearly with duration of use (p_trend = 0.01). Among postmenopausal women, ever use of MHT was associated with a nonsignificant increase in melanoma risk overall (HR = 1.14, 95% CI = 0.97–1.43), which was heterogeneous across countries (p_homogeneity = 0.05). Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations.     

Prospective study of physical activity in different periods of life and the risk of ovarian cancer

Only few studies have assessed the role of physical activity in the etiology of ovarian cancer, and the results have been inconclusive. We studied associations between physical activity and risk of ovarian cancer in 96,541 women aged 30-49 at enrollment in a prospective study in Norway and Sweden. Participants reported physical activity level at ages 14, 30 and at enrollment, and participation in competitive sports. Complete follow-up through 2001/2002 was achieved by linkage to national registries. The relation between physical activity and ovarian cancer incidence was assessed using multivariate Cox proportional hazard models. During an average 11.1 years of follow-up, there were 264 ovarian cancer cases (including 81 borderline tumors) diagnosed at a mean age of 49 years. Highly physically active women at cohort enrollment had a similar risk of ovarian cancer as women reporting no activity (multivariate relative risk RR = 1.08, 95% CI 0.53-2.18). Physical activity at age 30 or at age 14 did not either afford any protection from ovarian cancer, nor did a consistently high level of activity from younger ages until enrollment. Results were similar for invasive and borderline tumors, and for different subgroups of women classified according to other known risk factors for ovarian cancer. In our study of primarily premenopausal women, physical activity at different ages did neither reduce nor increase risk of ovarian cancer. In the context of the inconsistent scientific literature, our findings probably reflect that physical activity is not causally related with ovarian cancer.     

Postmenopausal hormone use and cutaneous melanoma risk: A French prospective cohort study

Cutaneous melanoma has been suspected to be influenced by female hormones. Several studies reported a positive association between menopausal hormone therapy (MHT) use and melanoma risk; however, previous findings were conflicting. We sought to explore the associations between MHT use and melanoma risk in a prospective cohort of women in France, where a particularly wide variety of MHT formulations are available. E3N is a prospective cohort of 98,995 French women aged 40–65 years in 1990. MHT use was assessed through biennial self-administered questionnaires. We used Cox proportional hazards regression models adjusted for age and skin cancer risk factors. Over 1990–2008, 444 melanoma cases were ascertained among 75,523 postmenopausal women. Ever use of MHT was associated with a higher melanoma risk (hazard ratio (HR) = 1.35, 95% confidence intervals (CI) = 1.07–1.71). The association was strongest among past users (HR = 1.55, CI = 1.17–2.07, homogeneity for past vs. recent use: p = 0.11), and users of MHT containing norpregnane derivatives (HR = 1.59, CI = 1.11–2.27), although with no heterogeneity across types of MHT (p = 0.13). Among MHT users, the association was similar across durations of use. However, a higher risk was observed when treatment onset occurred shortly after menopause (<6 months: HR = 1.55, CI = 1.16–2.07 vs. ≥2 years). Associations between MHT use and melanoma risk were similar after adjustment for UV exposure, although MHT users were more likely to report sunscreen use than nonusers. Our data do not support a strong association between MHT use and melanoma risk. Further investigation is needed to explore potential effect modification by UV exposure on this relationship.     

Alcohol intake and risk of thyroid cancer in the NIH-AARP Diet and Health Study

Background:

Certain studies suggest that alcohol may reduce the risk of thyroid cancer in women, but the effect in men remains unclear.

Methods:

We analysed the association between alcohol and thyroid cancer in a large (n=490 159) prospective NIH-AARP Diet and Health Study with self-reported beer, wine, and liquor intakes.

Results:

Over 7.5 years of follow-up (median), 170 men and 200 women developed thyroid cancer. Overall, the thyroid cancer risk decreased with greater alcohol consumption (⩾2 drinks per day vs none, relative risk=0.57, 95% CI 0.36–0.89, P-trend=0.01).

Conclusions:

These results suggest a potential protective role for alcohol consumption in thyroid cancer.     

Physical activity and lung cancer risk in the European Prospective Investigation into Cancer and Nutrition Cohort

Research conducted predominantly in male populations on physical activity and lung cancer has yielded inconsistent results. We examined this relationship among 416,277 men and women from the European Prospective Investigation into Cancer and Nutrition (EPIC). Detailed information on recent recreational, household and occupational physical activity, smoking habits and diet was assessed at baseline between 1992 and 2000. Relative risks (RR) were estimated using Cox regression. During 6.3 years of follow-up we identified 607 men and 476 women with incident lung cancer. We did not observe an inverse association between recent occupational, recreational or household physical activity and lung cancer risk in either males or females. However, we found some reduction in lung cancer risk associated with sports in males (adjusted RR = 0.71; 95% confidence interval 0.50-0.98; highest tertile vs. inactive group), cycling (RR = 0.73; 0.54-0.99) in females and non-occupational vigorous physical activity. For occupational physical activity, lung cancer risk was increased for unemployed men (adjusted RR = 1.57; 1.20-2.05) and men with standing occupations (RR = 1.35; 1.02-1.79) compared with sitting professions. There was no evidence of heterogeneity of physical activity associations across countries, or across any of the considered cofactors. For some histologic subtypes suggestive sex-specific reductions, limited by subgroup sizes, were observed, especially with vigorous physical activity. In total, our study shows no consistent protective associations of physical activity with lung cancer risk. It can be assumed that the elevated risks found for occupational physical activity are not produced mechanistically by physical activity itself but rather reflect exposure to occupation-related lung cancer risk factors.     

Body size and risk of renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Previous studies suggest that obesity is related to increased risk of renal cell carcinoma (RCC); however, only a few studies report on measures of central vs. peripheral adiposity. We examined the association between anthropometric measures, including waist and hip circumference and RCC risk among 348,550 men and women free of cancer at baseline from 8 countries of the European Prospective Investigation into Cancer and Nutrition (EPIC). During 6.0 years of follow-up we identified 287 incident cases of RCC. Relative risks were calculated using Cox regression, stratified by age and study center and adjusted for smoking status, education, alcohol consumption, physical activity, menopausal status, and hormone replacement therapy use. Among women, an increased risk of RCC was conferred by body weight (relative risk [RR] in highest vs. lowest quintile = 2.13; 95% confidence interval [CI] = 1.16-3.90; p-trend = 0.003), body mass index (BMI) (RR = 2.25; 95% CI = 1.14-4.44; p-trend = 0.009), and waist (RR = 1.67; 95% CI = 0.94-2.98; p-trend = 0.003) and hip circumference (RR = 2.30; 95% CI = 1.22-4.34; p-trend = 0.01); however, waist and hip circumference were no longer significant after controlling for body weight. Among men, hip circumference (RR = 0.44; 95% CI = 0.20-0.98; p-trend = 0.03) was related significantly to decreased RCC risk only after accounting for body weight. Height was not related significantly to RCC risk. Our findings suggest that obesity is related to increased risk of RCC irrespective of fat distribution among women, whereas low hip circumference is related to increased RCC risk among men. Our data give further credence to public health efforts aiming to reduce the prevalence of obesity to prevent RCC, in addition to other chronic diseases.     

Individual and joint use of statins and low-dose aspirin and risk of colorectal cancer: a population-based case-control study

Recent research has drawn attention to protective effects of statins on colorectal cancer (CRC) and possible joint effects with other drugs. Because statins are often administered in combination with low-dose aspirin for the prevention of cardiovascular disease, the aim of our study was to investigate individual and combined effects of statins and low-dose aspirin on CRC risk. We assessed use of statins and low-dose aspirin in 540 cases with histologically confirmed incident CRC and 614 control subjects in a population-based case-control study in Germany. Multiple logistic regression was used to estimate the impact of regular use of either low-dose aspirin or statins, and of both drugs combined on CRC risk. We found modest risk reduction of CRC for regular use of low-dose aspirin (adjusted odds ratio 0.77, 95% confidence interval 0.55-1.07) and a stronger association with regular use of statins (OR 0.65, 95% CI 0.43-0.99) or use of both drugs (OR 0.63, 95% CI 0.36-1.10). Combined use of low-dose aspirin and statins was associated with risk reduction by 62% after 5 or more years (OR 0.38, 95% CI 0.15-0.97). Combinational chemoprevention with low-dose aspirin and statins might provide stronger risk reduction than either of the single drugs after at least 5 years use, but confirmation is needed, preferably in prospective cohort studies and eventually by randomized controlled trials.     

Statin use and risk of nonmelanoma skin cancer: a nationwide study in Denmark

Background:

Evidence is conflicting regarding statin use and risk of basal cell (BCC) and squamous cell skin cancer (SCC).

Methods:

Using Danish nationwide registries, we identified all patients with incident BCC/SCC during 2005–2009 and matched them to population controls. We computed odds ratios (ORs) for BCC and SCC associated with statin use.

Results:

We identified 38 484 cases of BCC and 3724 cases of SCC. Statin ever use was associated with ORs of 1.09 (CI: 1.06–1.13) for BCC and 1.01 (CI: 0.91–1.11) for SCC.

Conclusions:

Statin use was not associated with risk of SCC. Residual confounding plausibly explains the marginally increased risk of BCC.     

Long-term antihypertensive drug use and risk of cancer: The Japan Public Health Center-based prospective study

Antihypertensive drugs have been reported as both promotors and suppressors of cancers and this relationship has been known for several decades. We examined a large-scale prospective cohort study in Japan to assess the relationship between long-term antihypertensive drug use, for 10 y, and carcinogenesis. We divided participants into 4 categories according to the period of antihypertensive drug use, and calculated the hazard ratios (HRs), 95% confidence intervals (CIs), and P trends using the Cox proportional hazard model. In all cancers, there was a significant difference in the medication period and the adjusted HR, as well as a significant difference in the P trend. Furthermore, more than 10 y use of antihypertensive drugs significantly increased the adjusted HR in colorectal cancer (multivariable HR: 1.18, 95% CI: 1.01-1.37 in the >10 y use group; P for trend = .033) and renal cancer (multivariable HR: 3.76, 95% CI: 2.32-6.10 in the 5-10 y use group; multivariable HR: 2.14, 95% CI: 1.29-3.56 in the >10 y use group; P for trend < .001). The highest adjusted HR in renal cancer among antihypertensive drug users was observed in the analysis performed on patients in which the outcomes were calculated from 3 y after the 10-y follow-up survey and by sex. A large-scale cohort study in Japan suggested that long-term use of antihypertensive drugs may be associated with an increased incidence of colorectal and renal cancer.     

Selenium and the risk of postmenopausal breast cancer in the DOM cohort

Summary Selenium has been claimed to have chemo-preventive properties. However, data showing that in humans selenium levels are already decreased prior to diagnosis of breast cancer were not available. Such information is mandatory before oral selenium supplementation in the primary prevention of (breast) cancer in humans is acceptable. This question of a preventive-potential of selenium was evaluated in a case-control study nested in a cohort, because this design allows determination of the time-order of preceding selenium levels and subsequent cancer risk.The cohort consisted of 5577 women aged 55–70 years from the DOM project, a population based breast cancer screening program in the Netherlands. Instrumental Neutron Activation Analysis was used to measure the selenium content of toenail clippings. The 69 cases of breast cancer found during follow-up after screening represent recent tumours since all women had a negative screening mammogram 3–5 years previously.No decreased selenium levels, as measured in nail clippings from the big toes, could be detected in cases-to-be, either when compared to 4 age matched controls per case or when compared with a random control group drawn from the entire cohort. On the contrary, a tendency for slightly higher selenium levels among future cancer cases was observed.As to the sensitivity of detecting differences in selenium by nail clippings, lower selenium could be detected in nails of current smokers. The smoking-related decrease in nail selenium level was of the same order as the differences between breast cancer cases and controls, but was independent of the breast cancer risk.Results are similar to a comparable study on premenopausal breast cancer and argue against a preventive role for selenium on breast cancer risk.     

Relation of statin use with non-melanoma skin cancer: prospective results from the Women's Health Initiative

Background:

The relationship between statin use and non-melanoma skin cancer (NMSC) is unclear with conflicting findings in literature. Data from the Women''s Health Initiative (WHI) Observational Study and WHI Clinical Trial were used to investigate the prospective relationship between statin use and NMSC in non-Hispanic white (NHW) postmenopausal women.

Methods:

The WHI study enrolled women aged 50–79 years at 40 US centres. Among 133 541 NHW participants, 118 357 with no cancer history at baseline and complete medication/covariate data comprised the analytic cohort. The association of statin use (baseline, overall as a time-varying variable, duration, type, potency, lipophilicity) and NMSC incidence was determined using random-effects logistic regression models.

Results:

Over a mean of 10.5 years of follow-up, we identified 11 555 NMSC cases. Compared with participants with no statin use, use of any statin at baseline was associated with significantly increased NMSC incidence (adjusted odds ratio (OR_adj) 1.21; 95% confidence interval (CI): 1.07–1.35)). In particular, lovastatin (OR 1.52; 95% CI: 1.08–2.16), simvastatin (OR 1.38; 95% CI: 1.12–1.69), and lipophilic statins (OR 1.39; 95% CI: 1.18–1.64) were associated with higher NMSC risk. Low and high, but not medium, potency statins were associated with higher NMSC risk. No significant effect modification of the statin–NMSC relationship was found for age, BMI, smoking, solar irradiation, vitamin D use, and skin cancer history.

Conclusions:

Use of statins, particularly lipophilic statins, was associated with increased NMSC risk in postmenopausal white women in the WHI cohort. The lack of duration–effect relationship points to possible residual confounding. Additional prospective research should further investigate this relationship.     

No association between green tea and prostate cancer risk in Japanese men: the Ohsaki Cohort Study

In a prospective study of 19,561 Japanese men, green-tea intake was not associated with a lower risk of prostate cancer (110 cases), the multivariate hazard ratio for men drinking > or =5 cups compared with <1 cup per day being 0.85 (95% confidence interval 0.50-1.43, trend P = 0.81).