Association between Melanocytic Nevi and Risk of Breast Diseases: The French E3N Prospective Cohort

Kvaskoff, Marina; Bijon, Anne; Mesrine, Sylvie; Vilier, Alice; Baglietto, Laura; Fournier, Agnès; Clavel‐Chapelon, Françoise; Dossus, Laure; Boutron‐Ruault, Marie‐Christine

doi:10.1371/journal.pmed.1001660

Cited by 12 publications

(12 citation statements)

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“…A correlated SNP rs738322 (r-sq=0.34, D’=0.71) located in the PLA2G6 gene has previously been associated with cutaneous nevi 20 . Interestingly, two recent independent studies recently reported a link between cutaneous nevi and breast cancer 21 , 22 and it is possible that this link can be partly explained through a shared genetic origin between cutaneous nevi and mammographic density.…”

Section: Resultsmentioning

confidence: 99%

Genome-wide association study identifies multiple loci associated with both mammographic density and breast cancer risk

et al. 2014

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Mammographic density reflects the amount of stromal and epithelial tissues in relation to adipose tissue in the breast and is a strong risk factor for breast cancer. Here we report the results from meta-analysis of genome-wide association studies (GWAS) of three mammographic density phenotypes: dense area, non-dense area and percent density in up to 7,916 women in stage 1 and an additional 10,379 women in stage 2. We identify genome-wide significant (P<5×10−8) loci for dense area (AREG, ESR1, ZNF365, LSP1/TNNT3, IGF1, TMEM184B, SGSM3/MKL1), non-dense area (8p11.23) and percent density (PRDM6, 8p11.23, TMEM184B). Four of these regions are known breast cancer susceptibility loci, and four additional regions were found to be associated with breast cancer (P<0.05) in a large meta-analysis. These results provide further evidence of a shared genetic basis between mammographic density and breast cancer and illustrate the power of studying intermediate quantitative phenotypes to identify putative disease susceptibility loci.

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Section: Resultsmentioning

confidence: 99%

Genome-wide association study identifies multiple loci associated with both mammographic density and breast cancer risk

et al. 2014

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“…46 In epidemiology studies, the association of TYRP1 with nevi and melanoma has been reported, 47, 48 and two studies also proposed that nevi (melanoma) and breast cancer may share genetic factors. 49, 50 Therefore, TYRP1 could be a candidate gene for different diseases through different mechanisms that require further studies to reveal.…”

Section: Discussionmentioning

confidence: 99%

Genetic variation in the vitamin D related pathway and breast cancer risk in women of African ancestry in the root consortium

Wang

Huo

Kupfer

et al. 2017

Intl Journal of Cancer

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The vitamin D related pathway has been evaluated in carcinogenesis but its genetic contribution remains poorly understood. We examined single-nucleotide polymorphisms (SNPs) in the vitamin D related pathway genes using data from a genome-wide association study (GWAS) of breast cancer in the African Diaspora that included 3,686 participants (1,657 cases). Pathwayand gene-level analyses were conducted using the adaptive rank truncated product test. Odds ratios (OR) and 95% confidence intervals (CI) were estimated at SNP-level. After stringent Bonferroni corrections, we observed no significant association between variants in the vitamin D pathway and breast cancer risk at the pathway-, gene-, or SNP-level. In addition, no association was found for either the reported signals from GWASs of vitamin D related traits, or the SNPs within vitamin D receptor (VDR) binding regions. Furthermore, a decrease in genetically predicted 25(OH)D levels by Mendelian randomization was not associated with breast cancer (p 5 0.23). However, an association for breast cancer with the pigment synthesis/metabolism pathway almost approached significance (pathway-level p 5 0.08), driven primarily by a nonsense SNP rs41302073 in TYRP1, with an OR of 1.54 (95% CI 5 1.24-1.91, p adj 5 0.007). In conclusion, we found no evidence to support an association between vitamin D status and breast cancer risk in women of African ancestry, suggesting that vitamin D is unlikely to have significant effect on breast carcinogenesis. Interestingly, TYRP1 might be related to breast cancer through a non-vitamin D relevant mechanism but further studies are needed.In vitro and in vivo studies strongly suggested that vitamin D status may have a protective effect against breast cancer because of its role in regulating cell proliferation, differentiation and apoptosis. 1,2 Epidemiology studies also reported that individuals with dark skin pigmentation like African American women have vitamin D deficiency, 3,4 and women of African ancestry experience higher breast cancer-specific mortality 5 and are more likely to present with estrogen receptor negative (ER-) tumors. 6 However, the correlation between vitamin D status and breast cancer is still unclear in population studies. 7,8

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“…Two previous studies found that women with more nevi were more likely to be diagnosed with breast cancer than their counterparts who reported no nevi, which suggested the number of cutaneous nevi may reflect plasma sex hormone levels [4,5]. In addition, postmenopausal women with six or more nevi had significantly higher levels of free oestradiol and free testosterone than those with no nevi, indicating the potential utility of nevi as a marker of postmenopausal women's endogenous sex hormone levels.…”

Section: Introductionmentioning

confidence: 96%

Associations between benign cutaneous nevi and risk of Type 2 diabetes mellitus in men and women: results from two prospective cohort studies

et al. 2016

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Aim To examine the association of cutaneous nevi with Type 2 diabetes risk. Methods We prospectivly examined the associations between nevus count and risk of Type 2 diabetes among 26 240 men (1988–2010) from the Health Professionals Follow-up Study and 67 050 women (1986–2010) from the Nurses’ Health Study. Information on the numbers of cutaneous nevi on arms at baseline and incident cases of Type 2 diabetes was collected using validated questionnaires. Results During 1 879 287 person-years of follow-up, we documented 9040 incident cases of Type 2 diabetes. After adjustment for age, BMI and other diabetes risk factors, greater number of nevi was associated with higher risk of Type 2 diabetes. Multivariable-adjusted hazard ratios for <1, 1–5, 6–14 and ≥ 15 nevi were 1.00 (reference), 1.02 (95% CI 0.93, 1.13), 1.08 (95% CI 0.88, 1.34) and 1.57 (95% CI 1.15, 2.15), respectively, for men (P for linear trend = 0.01), and 1.00 (reference), 1.07 (95% CI 1.02, 1.13), 0.98 (95% CI 0.87, 1.10), and 1.25 (1.01, 1.54), respectively, for women (P for linear trend = 0.05). This positive association remained consistent across subgroups stratified by age, BMI, multivitamin use, smoking status, alcohol, physical activity, history of hypercholesterolaemia, family history of diabetes, history of hypertension and menopausal status (in women). Conclusions Cutaneous nevus count may represent a novel marker for development of Type 2 diabetes, suggesting a possible unique melanocytic nevus-related mechanism in the pathogenesis of Type 2 diabetes. Further studies are warranted to confirm the findings and to investigate the underlying mechanisms.

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Association between Melanocytic Nevi and Risk of Breast Diseases: The French E3N Prospective Cohort

Abstract: Using data from the French E3N prospective cohort, Marina Kvaskoff and colleagues examine the association between number of cutaneous nevi and the risk for breast cancer. Please see later in the article for the Editors' Summary

Cited by 12 publications

References 64 publications

Genome-wide association study identifies multiple loci associated with both mammographic density and breast cancer risk

Genome-wide association study identifies multiple loci associated with both mammographic density and breast cancer risk

Genetic variation in the vitamin D related pathway and breast cancer risk in women of African ancestry in the root consortium

Associations between benign cutaneous nevi and risk of Type 2 diabetes mellitus in men and women: results from two prospective cohort studies

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