| 1. |
- Cervenka, Iris, et al.
(författare)
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Exogenous hormone use and cutaneous melanoma risk in women : The European Prospective Investigation into Cancer and Nutrition
- 2020
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 146:12, s. 3267-3280
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Tidskriftsartikel (refereegranskat)abstract
- 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 (phomogeneity = 0.42). This risk increased linearly with duration of use (ptrend = 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 (phomogeneity = 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.
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| 2. |
- Cramer, Daniel W., et al.
(författare)
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Anti-CA15.3 and Anti-CA125 Antibodies and ovarian cancer risk : Results from the EPIC cohort
- 2018
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Ingår i: Cancer Epidemiology Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 27:7, s. 790-804
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neoplastic and non-neoplastic events may raise levels of mucins, CA15.3, and CA125, and generate antibodies against them, but their impact on epithelial ovarian cancer (EOC) risk has not been fully defined. Methods: CA15.3, CA125, and IgG1 antibodies against them were measured in 806 women who developed EOC and 1,927 matched controls from the European Prospective Investigation of Nutrition and Cancer. Associations between epidemiologic factors and anti-mucin antibodies were evaluated using generalized linear models; EOC risks associated with anti-mucin antibodies, by themselves or in combination with respective antigens, were evaluated using conditional logistic regression. Results: In controls, lower antibodies against both mucins were associated with current smoking; and, in postmenopausal women, higher levels with longer oral contraceptive use and later-age-at and shorter-interval-since last birth. Lower anti-CA15.3 antibodies were associated with higher body mass and, in premenopausal women, more ovulatory cycles. Higher anti-CA15.3 and anti-CA125 antibodies were associated with higher risk for mucinous EOC occurring ≥ 3 years from enrollment. Long-term risk for serous EOC was reduced in women with low CA125 and high anti-CA125 antibodies relative to women with low concentrations of both. Conclusions: We found general support for the hypothesis that anti-mucin antibody levels correlate with risk factors for EOC. Antibodies alone or in combinations with their antigen may predict longer term risk of specific EOC types. Impact: Anti-CA125 and anti-CA15.3 antibodies alone or in perspective of antigens may be informative in the pathogenesis of EOC subtypes, but less useful for informing risk for all EOC.
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| 3. |
- Fortner, Renee T., et al.
(författare)
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Correlates of circulating ovarian cancer early detection markers and their contribution to discrimination of early detection models : results from the EPIC cohort
- 2017
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Ingår i: Journal of Ovarian Research. - : Springer Science and Business Media LLC. - 1757-2215. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ovarian cancer early detection markers CA125, CA15.3, HE4, and CA72.4 vary between healthy women, limiting their utility for screening.Methods: We evaluated cross-sectional relationships between lifestyle and reproductive factors and these markers among controls (n = 1910) from a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC). Improvements in discrimination of prediction models adjusting for correlates of the markers were evaluated among postmenopausal women in the nested case-control study (n = 590 cases). Generalized linear models were used to calculate geometric means of CA125, CA15.3, and HE4. CA72.4 above vs. below limit of detection was evaluated using logistic regression. Early detection prediction was modeled using conditional logistic regression.Results: CA125 concentrations were lower, and CA15.3 higher, in post- vs. premenopausal women (p ≤ 0.02). Among postmenopausal women, CA125 was higher among women with higher parity and older age at menopause (ptrend ≤ 0.02), but lower among women reporting oophorectomy, hysterectomy, ever use of estrogen-only hormone therapy, or current smoking (p < 0.01). CA15.3 concentrations were higher among heavier women and in former smokers (p ≤ 0.03). HE4 was higher with older age at blood collection and in current smokers, and inversely associated with OC use duration, parity, and older age at menopause (≤ 0.02). No associations were observed with CA72.4. Adjusting for correlates of the markers in prediction models did not improve the discrimination.Conclusions: This study provides insights into sources of variation in ovarian cancer early detection markers in healthy women and informs about the utility of individualizing marker cutpoints based on epidemiologic factors.
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| 4. |
- Fortner, Renée T., et al.
(författare)
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Ovarian cancer early detection by circulating CA125 in the context of anti-CA125 autoantibody levels : Results from the EPIC cohort
- 2018
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 142:7, s. 1355-1360
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Tidskriftsartikel (refereegranskat)abstract
- CA125 is the best ovarian cancer early detection marker to date; however, sensitivity is limited and complementary markers are required to improve discrimination between ovarian cancer cases and non-cases. Anti-CA125 autoantibodies are observed in circulation. Our objective was to evaluate whether these antibodies (1) can serve as early detection markers, providing evidence of an immune response to a developing tumor, and (2) modify the discriminatory capacity of CA125 by either masking CA125 levels (resulting in lower discrimination) or acting synergistically to improve discrimination between cases and non-cases. We investigated these objectives using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort (EPIC) including 250 cases diagnosed within 4 years of blood collection and up to four matched controls. Circulating CA125 antigen and antibody levels were quantified using an electrochemiluminescence assay. Adjusted areas under the curve (aAUCs) by 2-year lag-time intervals were calculated using conditional logistic regression calibrated toward the absolute risk estimates from a pre-existing epidemiological risk model as an offset-variable. Anti-CA125 levels alone did not discriminate cases from controls. For cases diagnosed <2 years after blood collection, discrimination by CA125 antigen was suggestively higher with higher anti-CA125 levels (aAUC, highest antibody tertile: 0.84 [0.76-0.92]; lowest tertile: 0.76 [0.67-0.86]; p(het)=0.06). We provide the first evidence of potentially synergistic discrimination effects of CA125 and anti-CA125 antibodies in ovarian early detection. If these findings are replicated, evaluating CA125 in the context of its antibody may improve ovarian cancer early detection. What's new? Although CA125, a mucin produced in epithelial cells, is a known marker for ovarian cancer, complementary biomarkers are necessary for reliable early cancer detection. Here, the authors examined autoantibodies against CA125 as potential pre-diagnosis markers. Although anti-CA125 levels did not discriminate between ovarian cases and controls, discrimination of CA125 differed by levels of its antibody, with the highest discrimination among women with the highest antibody levels. The authors propose that CA125 and anti-CA125 may act synergistically for ovarian cancer early detection.
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| 5. |
- Mahamat-Saleh, Yahya, et al.
(författare)
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Baseline and lifetime alcohol consumption and risk of skin cancer in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC)
- 2023
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 152:3, s. 348-362
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Tidskriftsartikel (refereegranskat)abstract
- 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; Ptrend =.001), BCC (HR = 1.12, 95% CI = 1.01-1.23; Ptrend =.04), and melanoma risks in men (HR = 1.17, 95% CI = 0.95-1.44; Ptrend =.17), while associations were more modest in women (SCC: HR = 1.09, 95% CI = 0.90-1.30; Ptrend =.13; BCC: HR = 1.08, 95% CI = 1.00-1.17, Ptrend =.03; melanoma: HR = 0.93, 95% CI = 0.80-1.08, Ptrend =.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; Ptrend =.0009) and BCC risks in men (HR = 1.17, 95% CI = 1.04-1.31; Ptrend =.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.
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| 6. |
- Mahamat-Saleh, Yahya, et al.
(författare)
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Citrus intake and risk of skin cancer in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC)
- 2020
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 35:11, s. 1057-1067
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Tidskriftsartikel (refereegranskat)abstract
- Citrus intake has been suggested to increase the risk of skin cancer. Although this relation is highly plausible biologically, epidemiologic evidence is lacking. We aimed to examine the potential association between citrus intake and skin cancer risk. EPIC is an ongoing multi-center prospective cohort initiated in 1992 and involving ~ 520,000 participants who have been followed-up in 23 centers from 10 European countries. Dietary data were collected at baseline using validated country-specific dietary questionnaires. We used Cox proportional hazards regression models to compute hazard ratios (HR) and 95% confidence intervals (CI). During a mean follow-up of 13.7 years, 8448 skin cancer cases were identified among 270,112 participants. We observed a positive linear dose–response relationship between total citrus intake and skin cancer risk (HR = 1.10, 95% CI 1.03–1.18 in the highest vs. lowest quartile; Ptrend = 0.001), particularly with basal cell carcinoma (BCC) (HR = 1.11, 95% CI 1.02–1.20, Ptrend = 0.007) and squamous cell carcinoma (SCC) (HR = 1.23, 95% CI 1.04–1.47, Ptrend = 0.01). Citrus fruit intake was positively associated with skin cancer risk (HR = 1.08, 95% CI 1.01–1.16, Ptrend = 0.01), particularly with melanoma (HR = 1.23, 95% CI 1.02–1.48; Ptrend = 0.01), although with no heterogeneity across skin cancer types (Phomogeneity = 0.21). Citrus juice was positively associated with skin cancer risk (Ptrend = 0.004), particularly with BCC (Ptrend = 0.008) and SCC (Ptrend = 0.004), but not with melanoma (Phomogeneity = 0.02). Our study suggests moderate positive linear dose–response relationships between citrus intake and skin cancer risk. Studies with available biomarker data and the ability to examine sun exposure behaviors are warranted to clarify these associations and examine the phototoxicity mechanisms of furocoumarin-rich foods.
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| 7. |
- Zuo, Hui, et al.
(författare)
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Results from the European Prospective Investigation into Cancer and Nutrition Link Vitamin B6 Catabolism and Lung Cancer Risk
- 2018
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 78:1, s. 302-308
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Tidskriftsartikel (refereegranskat)abstract
- Circulating pyridoxal-5′-phosphate (PLP) has been linked to lung cancer risk. The PAr index, defined as the ratio 4-pyridoxic acid/(pyridoxal + PLP), reflects increased vitamin B6 catabolism during inflammation. PAr has been defined as a marker of lung cancer risk in a prospective cohort study, but analysis of a larger numbers of cases are needed to deepen the significance of this study. Here, we conducted a nested case–control study within the European Prospective Investigation into Cancer and Nutrition (EPIC, n = 521,330), which included 892 incident lung cancer cases and 1,748 controls matched by center, gender, date of blood collection, and date of birth. The association of PAr with risk of lung cancer was evaluated by using conditional logistic regression. Study participants with elevated PAr experienced higher risk of lung cancer in a dose–response fashion, with a doubling in PAr levels associated with 52% higher odds of lung cancer after adjustment for tobacco smoking, serum cotinine levels, educational attainment, and BMI [OR, 1.52; 95% confidence interval (CI) 1.27–1.81; P < 0.001]. Additional adjustment for intake of vegetables and fruits and physical activity did not materially affect risk association. The association of PAr with lung cancer risk was similar in both genders but slightly stronger in former smokers and in participants diagnosed with squamous cell carcinoma. This study provides robust evidence that increased vitamin B6 catabolism is independently associated with a higher risk of future lung cancer.
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