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.     

Baseline and lifetime alcohol consumption and risk of skin cancer in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC)

Experimental evidence suggests that alcohol induces cutaneous carcinogenesis, yet epidemiological studies on the link between alcohol intake and skin cancer have been inconsistent. The European Prospective Investigation into Cancer and Nutrition (EPIC) is a prospective cohort initiated in 1992 in 10 European countries. Alcohol intake at baseline and average lifetime alcohol intake were assessed using validated country-specific dietary and lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated in Cox models. A total of 14 037 skin cancer cases (melanoma: n = 2457; basal-cell carcinoma (BCC): n = 8711; squamous-cell carcinoma (SCC): n = 1928; unknown: n = 941) were identified among 450 112 participants (average follow-up: 15 years). Baseline alcohol intake was positively associated with SCC (>15 vs 0.1-4.9 g/day: HR = 1.44, 95% CI = 1.17-1.77; P_trend = .001), BCC (HR = 1.12, 95% CI = 1.01-1.23; P_trend = .04), and melanoma risks in men (HR = 1.17, 95% CI = 0.95-1.44; P_trend = .17), while associations were more modest in women (SCC: HR = 1.09, 95% CI = 0.90-1.30; P_trend = .13; BCC: HR = 1.08, 95% CI = 1.00-1.17, P_trend = .03; melanoma: HR = 0.93, 95% CI = 0.80-1.08, P_trend = .13). Associations were similar for lifetime alcohol intake, with an attenuated linear trend. Lifetime liquor/spirit intake was positively associated with melanoma (fourth vs first quartile: HR = 1.47, 95% CI = 1.08-1.99; P_trend = .0009) and BCC risks in men (HR = 1.17, 95% CI = 1.04-1.31; P_trend = .14). Baseline and lifetime intakes of wine were associated with BCC risk (HR = 1.25 in men; HR = 1.11-1.12; in women). No statistically significant associations were found between beverage types and SCC risk. Intake of beer was not associated with skin cancer risk. Our study suggests positive relationships between alcohol intake and skin cancer risk, which may have important implications for the primary prevention of skin cancer.     

Reproductive factors,exogenous hormone use and risk of hepatocellular carcinoma among US women: results from the Liver Cancer Pooling Project

Background:

Hepatocellular carcinoma (HCC) occurs less commonly among women than men in almost all regions of the world. The disparity in risk is particularly notable prior to menopause suggesting that hormonal exposures during reproductive life may be protective. Exogenous oestrogenic exposures such as oral contraceptives (OCs), however, have been reported to increase risk, suggesting that estrogens may be hepatocarcinogenic. To examine the effects of reproductive factors and exogenous hormones on risk, we conducted a prospective analysis among a large group of US women.

Methods:

In the Liver Cancer Pooling Project, a consortium of US-based cohort studies, data from 799 500 women in 11 cohorts were pooled and harmonised. Cox proportional hazards regression models were used to generate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of reproductive factors and exogenous hormones with HCC (n=248).

Results:

Bilateral oophorectomy was associated with a significantly increased risk of HCC (HR=2.67, 95% CI=1.22–5.85), which did not appear to be related to a shorter duration of exposure to endogenous hormones or to menopausal hormone therapy use. There was no association between OC use and HCC (HR=1.12, 95% CI=0.82–1.55). Nor were there associations with parity, age at first birth, age at natural menopause, or duration of fertility.

Conclusions:

The current study suggests that bilateral oophorectomy increases the risk of HCC but the explanation for the association is unclear. There was no association between OC use and HCC risk. Examination of endogenous hormone levels in relation to HCC may help to clarify the findings of the current study.     

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.     

Oral contraceptives, reproductive history and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition

Background:

Oral contraceptive use and reproductive factors may initiate long-term changes to the hormonal milieu and thereby, possibly influence colorectal cancer risk.

Methods:

We examined the association of hormonal and reproductive factors with risk of colorectal cancer among 337 802 women in the European Prospective Investigation into Cancer and Nutrition, of whom 1878 developed colorectal cancer.

Results:

After stratification for center and age, and adjustment for body mass index, smoking, diabetes mellitus, physical activity and alcohol consumption, ever use of oral contraceptives was marginally inversely associated with colorectal cancer risk (hazard ratio (HR), 0.92; 95% confidence interval (CI), 0.83–1.02), although this association was stronger among post-menopausal women (HR, 0.84; 95% CI: 0.74–0.95). Duration of oral contraceptive use and reproductive factors, including age at menarche, age at menopause, type of menopause, ever having an abortion, parity, age at first full-term pregnancy and breastfeeding, were not associated with colorectal cancer risk.

Conclusion:

Our findings provide limited support for a potential inverse association between oral contraceptives and colorectal cancer risk.     

Menopausal hormone therapy and breast cancer risk: Impact of different treatments. The European Prospective Investigation into Cancer and Nutrition

Menopausal hormone therapy (MHT) is characterized by use of different constituents, regimens and routes of administration. We investigated the association between the use of different types of MHT and breast cancer risk in the EPIC cohort study. The analysis is based on data from 133,744 postmenopausal women. Approximately 133,744 postmenopausal women contributed to this analysis. Information on MHT was derived from country‐specific self‐administered questionnaires with a single baseline assessment. Incident breast cancers were identified through population cancer registries or by active follow‐up (mean: 8.6 yr). Overall relative risks (RR) and 95% confidence interval (CI) were derived from country‐specific Cox proportional hazard models estimates. A total of 4312 primary breast cancers were diagnosed during 1,153,747 person‐years of follow‐up. Compared with MHT never users, breast cancer risk was higher among current users of estrogen only (RR: 1.42, 95% CI 1.23–1.64) and higher still among current users of combined MHT (RR: 1.77, 95% CI 1.40–2.24; p = 0.02 for combined vs. estrogen‐only). Continuous combined regimens conferred a 43% (95% CI: 19–72%) greater risk compared with sequential regimens. There was no significant difference between progesterone and testosterone derivatives in sequential regimens. There was no significant variation in risk linked to the estrogenic component of MHT, neither for oral vs. cutaneous administration nor for estradiol compounds vs. conjugated equine estrogens. Estrogen‐only and combined MHT uses were associated with increased breast cancer risk. Continuous combined preparations were associated with the highest risk. Further studies are needed to disentangle the effects of the regimen and the progestin component.     

Exogenous hormone use and meningioma risk

The decision to commence or continue use of hormone replacement therapy or oral contraceptives in women presumed or known to be diagnosed with intracranial meningioma is a common clinical question in neurosurgery. A review of the English-language literature was undertaken to examine the association between the use of exogenous hormones and meningioma risk. Seven publications were identified, 6 of which met criteria for inclusion. No randomized clinical trial data were available, hence, results were collected from 2 population-based case-control studies, 2 hospital-based case-control studies, 1 nested case-control study drawn from a large national cohort, and 1 retrospective cohort study. At present, there is no statistical evidence of an increased risk of meningioma among users of oral contraceptives. Although not definitive, available data suggest an association between the use of hormone replacement therapy and increased meningioma risk. Further evaluation of exogenous hormone use in women with meningioma is needed with particular attention to stratification by hormone (ie, estrogen and/or progesterone) composition, duration of and age at use as well as tumor receptor subtype.     

Exogenous hormone use,reproductive history and risk of adult myeloid leukaemia

Background:

A hormonal aetiology is one explanation for the lower incidence of myeloid leukaemia in women compared with men.

Methods:

In this population-based case–control study, we evaluated associations between exogenous hormone use and reproductive history and myeloid leukaemia, overall and by disease subtype.

Results:

We observed a suggestive association between oral contraceptive use and acute myeloid leukaemia (odds ratio=0.55, 95% confidence interval=0.32–0.96). Hormone replacement therapy and reproductive factors were not associated with risk.

Conclusion:

Despite the biological plausibility for a role of oestrogen in leukaemogenesis, other aetiologic factors are likely to explain the differing incidence rates in males and females.     

Exogenous hormone use and the risk of postmenopausal breast cancer: results from the Netherlands Cohort Study

The association between the use of exogenous hormones as either oral contraceptives (OC) or hormone replacement therapy (HRT) in relation to postmenopausal breast cancer incidence was examined in the Netherlands Cohort Study (NLCS) among 62,573 women aged 55 to 69 years. Information on these types of exogenous hormone use and other risk factors was collected by mailed questionnaire. During 3.3 years of follow-up, 471 incident breast cancer cases were identified. After adjustment for traditional breast cancer risk factors, the relative risk (RR) of breast cancer was 1.09 (95 percent confidence interval [CI]=0.79–1.48) for women who ever used OCs cf women who never used OCs. The relative rates (with CIs) for women who used OCs for a period < 5 years, 5–9 years, 10–14 years, and 15+ years were 0.97 (0.61–1.55), 1.20 (0.69–2.07), 1.03 (0.60–1.77), and 1.96 (0.99–3.89), respectively. The test for trend was not significant (P=0.13). There was no evidence of any association between the number of years between the first and the last use of OCs and breast cancer incidence. In the subgroup of women with first-degree relatives with breast cancer, the RR for breast cancer associated with ever use of OCs was 1.51 (CI=0.67–3.41), whereas in the remaining women, the RR was 0.97 (CI=0.73–1.27). Ever-use of HRT compared with never-use was not associated with an increase in breast cancer risk in the multivariate analysis (RR=0.99, CI=0.68–1.43). Also, the number of years of HRT use was not associated with an increased breast cancer risk (trend P=0.83), nor was the number of years between the first and the last use of HRT and breast cancer incidence. One subgroup of women in which the use of HRT seemed associated (but not significantly) with an increase in breast cancer risk was women with an induced menopause (RR=1.72, CI=0.95–3.12). The RR of breast cancer for women who had ever used both OCs and HRT, compared with women who never used these exogenous hormones was 1.00 (CI=0.51–1.94). From this study, it cannot be concluded that the use of exogenous hormones is a strong risk factor for the development of postmenopausal breast cancer.Since the acceptance of this paper, two other papers have been published on HRT and breast cancer. For HRT (estrogen alone), one supports our finding of no association (Stanford et al, JAMA 1995; 274: 137–42) and one did find a positive association for current use (Colditz et al, New Engl J Med 1995; 332: 1589–93), most pronounced in older women with longer durations of use. With regard to use of combined estrogen-progestin HRT, the results in both papers were comparable to those for estrogen alone. More research on (combinations of) types of hormones is needed.This work was supported by the Dutch Cancer Society.     

Oral contraceptive use and risk of cutaneous malignant melanoma in a case-control study of French women

We report the results of a case-control study designed to analyze the relationship between oral contraceptive use (OC) and the risk of cutaneous malignant melonama (MM) in 240 White women under the age of 45. Five French centers participated in the study between February 1982 and January 1987 for periods of eight to 54 months, depending on the center. Cases were 91 consecutive newly diagnosed patients with histologically verified MM. Each case was matched with one or two controls on year of birth, date of interview, and treatment center. Controls were 149 patients with either malignant or nonmalignant disease who came to the center for diagnosis and treatment. Odds ratios (OR) were estimated by multivariate analyses taking into account age at menarche, sunlight exposure, and skin characteristics. No significant relation was found between the risk of MM and the total duration of OC use, age at start of use, and elapsed time since the first OC use. However, when the analysis was restricted to women aged 30–40 years, i.e., those who were able to use OC for 10 years or more, or who had started OC use 15 years or more before the diagnosis, the risk of MM increased significantly with the duration of OC use (P=0.03). A total of more than 4,000 hours of sunlight exposure, and menarche before the age of 14 also were found to increase significantly the risk of MM (OR=5.4, 95 percent confidence interval [CI]=1.6–18.3; and OR=3.6, CI=1.0–12.5, respectively).This study was made possible by a grant from the Institut Goustave Roussy (Contract no. 85-D-9).     

Oral contraceptive use and reproductive factors and risk of ovarian cancer in the European Prospective Investigation into Cancer and Nutrition

Background:

It is well established that parity and use of oral contraceptives reduce the risk of ovarian cancer, but the associations with other reproductive variables are less clear.

Methods:

We examined the associations of oral contraceptive use and reproductive factors with ovarian cancer risk in the European Prospective Investigation into Cancer and Nutrition. Among 327 396 eligible women, 878 developed ovarian cancer over an average of 9 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models stratified by centre and age, and adjusted for smoking status, body mass index, unilateral ovariectomy, simple hysterectomy, menopausal hormone therapy, and mutually adjusted for age at menarche, age at menopause, number of full-term pregnancies and duration of oral contraceptive use.

Results:

Women who used oral contraceptives for 10 or more years had a significant 45% (HR, 0.55; 95% CI, 0.41–0.75) lower risk compared with users of 1 year or less (P-trend, <0.01). Compared with nulliparous women, parous women had a 29% (HR, 0.71; 95% CI, 0.59–0.87) lower risk, with an 8% reduction in risk for each additional pregnancy. A high age at menopause was associated with a higher risk of ovarian cancer (>52 vs ⩽45 years: HR, 1.46; 95% CI, 1.06–1.99; P-trend, 0.02). Age at menarche, age at first full-term pregnancy, incomplete pregnancies and breastfeeding were not associated with risk.

Conclusion:

This study shows a strong protective association of oral contraceptives and parity with ovarian cancer risk, a higher risk with a late age at menopause, and no association with other reproductive factors.     

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.     

Oral contraceptive use and risk of melanoma in premenopausal women.

Melanoma has been increasing in white populations. Incidence rates rise steeply in women until about age 50, suggesting oestrogen as a possible risk factor. Oestrogens can increase melanocyte count and melanin content and cause hyperpigmentation of the skin. We examined prospectively the association between oral contraceptive (OC) use and diagnoses of superficial spreading and nodular melanoma among 183,693 premenopausal white women in the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHS II) cohorts. One hundred and forty six cases were confirmed in NHS during follow-up from 1976 to 1994, and 106 cases were confirmed in NHS II from 1989 to 1995. Skin reaction to sun exposure, sunburn history, mole counts, hair colour, family history of melanoma, parity, height and body mass index were also assessed and included in logistic regression models. A significant twofold increase in risk of melanoma (relative risk (RR) = 2.0, 95% confidence interval (CI) 1.2-3.4) was observed among current OC users compared to never users. Risk was further increased among current users with 10 or more years of use (RR = 3.4, 95% CI 1.7-7.0). Risk did not appear elevated among past OC users, even among those with longer durations of use, and risk did not decline linearly with time since last use. In conclusion, risk of premenopausal melanoma may be increased among women who are current OC users, particularly among those with longer durations of use. Further research is needed to determine whether low-dose oestrogen pills in particular are associated with an increase in risk and to describe possible interactions between OC use and sun exposure or other risk factors for melanoma.     

Tobacco smoke and bladder cancer--in the European Prospective Investigation into Cancer and Nutrition

The purpose of the present study was to investigate the association between smoking and the development of bladder cancer. The study population consisted of 429,906 persons participating in the European Prospective Investigation into Cancer and Nutrition (EPIC), 633 of whom developed bladder cancer during the follow-up period. An increased risk of bladder cancer was found for both current- (incidence rate ratio 3.96, 95% confidence interval: 3.07-5.09) and ex- (2.25, 1.74-2.91) smokers, compared to never-smokers. A positive association with intensity (per 5 cigarettes) was found among current-smokers (1.18, 1.09-1.28). Associations (per 5 years) were observed for duration (1.14, 1.08-1.21), later age at start (0.75, 0.66-0.85) and longer time since quitting (0.92, 0.86-0.98). Exposure to environmental tobacco smoke (ETS) during childhood increased the risk of bladder cancer (1.38, 1.00-1.90), whereas for ETS exposure as adult no effect was detected. The present study confirms the strong association between smoking and bladder cancer. The indication of a higher risk of bladder cancer for those who start smoking at a young age and for those exposed to ETS during childhood adds to the body of evidence suggesting that children are more sensitive to carcinogens than adults.     

Oral contraceptive use and risk of cutaneous malignant melanoma

The relation between cutaneous malignant melanoma (MM) and the use of oral contraceptives (OC) was investigated in a case-control study carried out from 1979 to 1991 among patients in hospitals and clinics in the Philadelphia (PA) and New York City (NY) metropolitan areas (United States). Cases were 615 women under age 70 who recently had been diagnosed with invasive melanoma; controls were 2,107 women of the same ages who had been treated for other conditions unrelated either to OC use or to skin diseases. The cases were categorized as severe or nonsevere based on the depth of invasion of the tumor or the presence or absence of metastases. Among the severe cases, OC use was not associated with MM: the relative risk (RR) estimate for ever-use was 1.1 (95 percent confidence interval [CI]=0.8–1.5) and the estimate for 10 or more years of use was 1.1 (CI=0.6–2.1). Nor was risk associated with recent use, long latency, or young age at first use. Among the nonsevere cases, ever-use of oral contraceptives was associated positively with MM (RR=1.5, CI=1.1–2.4) but there was no trend with increased duration of use. The findings provide evidence against the hypothesis that OC use increases the risk of malignant melanoma. The elevated estimates among the nonsevere cases most likely reflect selection bias rather than a causal relation.This research was supported in part by the US National Cancer Institute (grant R01 CA 45762). Additional support was provided by the US Food and Drug Administration (FD-U-000082); the views expressed do not necessarily represent the views of the Food and Drug Administration. The Slone Epidemiology Unit receives general support from Hoffmann-LaRoche, Inc. and Marion-Merrell Dow, Inc.     

Combined effect of oral contraceptive use and hormone replacement therapy on breast cancer risk in postmenopausal women

OBJECTIVE: We examined breast cancer risk related to lifetime exposure to oral contraceptives (OCs) and hormone replacement therapy (HRT) in postmenopausal women. METHODS: The Women's Contraceptive and Reproductive Experiences (CARE) Study was a population-based case-control study that included 1847 postmenopausal women with incident invasive breast cancer, and 1932 control subjects, identified using random digit dialing. RESULTS: 45% of cases and 49% of controls used both OCs and HRT. OC users were not at increased risk regardless of subsequent HRT exposure. HRT users who had used OCs previously did not have a higher risk of breast cancer than women with no exposure to OCs. We observed a negative interaction (p-value: 0.032) of combined hormone replacement therapy (CHRT) and past OC use. The increase in risk with CHRT was stronger in women who had never used OCs in the past (odds ratio: 1.05; 95% confidence interval: 1.01-1.10 per year of exclusive CHRT use) than in women who had used OCs (odds ratio: 1.00; 95% confidence interval: 0.97-1.03). CONCLUSIONS: We found no indication that adverse effects of exposure to OCs or HRT appeared only in the presence of the other hormone or were exacerbated by exposure to the other hormone.     

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.     

Smoking and the risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition

Background:

Smoking is not associated with prostate cancer incidence in most studies, but associations between smoking and fatal prostate cancer have been reported.

Methods:

During 1992 and 2000, lifestyle information was assessed via questionnaires and personal interview in a cohort of 145 112 European men. Until 2009, 4623 incident cases of prostate cancer were identified, including 1517 cases of low-grade, 396 cases of high grade, 1516 cases of localised, 808 cases of advanced disease, and 432 fatal cases. Multivariable Cox proportional hazards regression models were used to examine the association of smoking status, smoking intensity, and smoking duration with the risk of incident and fatal prostate cancer.

Results:

Compared with never smokers, current smokers had a reduced risk of prostate cancer (RR=0.90, 95% CI: 0.83–0.97), which was statistically significant for localised and low-grade disease, but not for advanced or high-grade disease. In contrast, heavy smokers (25+ cigarettes per day) and men who had smoked for a long time (40+ years) had a higher risk of prostate cancer death (RR=1.81, 95% CI: 1.11–2.93; RR=1.38, 95% CI: 1.01–1.87, respectively).

Conclusion:

The observation of an increased prostate cancer mortality among heavy smokers confirms the results of previous prospective studies.     

Inflammatory potential of the diet and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study

Proinflammatory diets are associated with risk of developing colorectal cancer (CRC), however, inconsistencies exist in subsite- and sex-specific associations. The relationship between CRC and combined lifestyle-related factors that contribute toward a low-grade inflammatory profile has not yet been explored. We examined the association between the dietary inflammatory potential and an inflammatory profile and CRC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. This cohort included 476,160 participants followed-up of 14 years and 5,991 incident CRC cases (3,897 colon and 2,094 rectal tumors). Dietary inflammatory potential was estimated using an Inflammatory Score of the Diet (ISD). An Inflammatory Profile Score (IPS) was constructed, incorporating the ISD, physical activity level and abdominal obesity. The associations between the ISD and CRC and IPS and CRC were assessed using multivariable regression models. More proinflammatory diets were related to a higher CRC risk, particularly for colon cancer; hazard ratio (HR) for highest versus lowest ISD quartile was 1.15 (95% confidence interval [CI] 1.04–1.27) for CRC, 1.24 (95% CI 1.09–1.41) for colon cancer and 0.99 (95% CI 0.83–1.17) for rectal cancer. Associations were more pronounced in men and not significant in women. The IPS was associated with CRC risk, particularly colon cancer among men; HRs for the highest versus lowest IPS was 1.62 (95% CI 1.31–2.01) for colon cancer overall and 2.11 (95% CI 1.50–2.97) for colon cancer in men. Our study shows that more proinflammatory diets and a more inflammatory profile are associated with higher risk of CRC, principally colon cancer and in men.     

Hormonal factors and pancreatic cancer risk in women: The Malmö Diet and Cancer Study

The incidence of pancreatic cancer is leveling between sexes. Smoking, high age and heredity are established risk factors, but evidence regarding the influence of hormonal factors is unclear. In this study, we investigated the associations of reproductive factors, use of oral contraceptives (OC) and hormone replacement therapy (HRT) with pancreatic cancer risk in the Malmö Diet and Cancer Study, a prospective, population‐based cohort encompassing 17,035 women. Up until 31 December 2015, 110 women were identified with incident pancreatic cancer through the Swedish Cancer Registry. Higher age at menarche was significantly associated with pancreatic cancer risk (age‐adjusted [hazard ratio] HR = 1.17; 95% confidence interval [CI] 1.04–1.32, and fully adjusted HR = 1.17; 95% CI 1.04–1.32). Ever use of OC was not significantly associated with pancreatic cancer risk but ever use of HRT was significantly associated with a decreased risk of pancreatic cancer (age‐adjusted HR = 0.47, 95% CI 0.23–0.97, and fully adjusted HR = 0.48, 95% CI 0.23–1.00), in particular use of estrogen‐only regimen (age‐adjusted HR = 0.21; 95% CI 0.05–0.87 and fully adjusted HR = 0.22; 95% CI 0.05–0.90). Age at menopause or first childbirth, parity and breastfeeding history were not significantly associated with pancreatic cancer risk. Collectively, these findings suggest a protective role of female hormones against pancreatic cancer. Further studies are needed, and potential modifying genetic factors and indirect hazardous effects of smoking should also be considered.