Association between Melanocytic Nevi and Risk of Breast Diseases: The French E3N Prospective Cohort
Background:
While melanocytic nevi have been associated with genetic factors and childhood sun exposure, several observations also suggest a potential hormonal influence on nevi. To test the hypothesis that nevi are associated with breast tumor risk, we explored the relationships between number of nevi and benign and malignant breast disease risk.
Methods and Findings:
We prospectively analyzed data from E3N, a cohort of French women aged 40–65 y at inclusion in 1990. Number of nevi was collected at inclusion. Hazard ratios (HRs) for breast cancer and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. Associations of number of nevi with personal history of benign breast disease (BBD) and family history of breast cancer were estimated using logistic regression. Over the period 15 June 1990–15 June 2008, 5,956 incident breast cancer cases (including 5,245 invasive tumors) were ascertained among 89,902 women. In models adjusted for age, education, and known breast cancer risk factors, women with “very many” nevi had a significantly higher breast cancer risk (HR = 1.13, 95% CI = 1.01–1.27 versus “none”; ptrend = 0.04), although significance was lost after adjustment for personal history of BBD or family history of breast cancer. The 10-y absolute risk of invasive breast cancer increased from 3,749 per 100,000 women without nevi to 4,124 (95% CI = 3,674–4,649) per 100,000 women with “very many” nevi. The association was restricted to premenopausal women (HR = 1.40, ptrend = 0.01), even after full adjustment (HR = 1.34, ptrend = 0.03; phomogeneity = 0.04), but did not differ according to breast cancer type or hormone receptor status. In addition, we observed significantly positive dose–response relationships between number of nevi and history of biopsy-confirmed BBD (n = 5,169; ptrend<0.0001) and family history of breast cancer in first-degree relatives (n = 7,472; ptrend = 0.0003). The main limitations of our study include self-report of number of nevi using a qualitative scale, and self-reported history of biopsied BBD.
Conclusions:
Our findings suggest associations between number of nevi and the risk of premenopausal breast cancer, BBD, and family history of breast cancer. More research is warranted to elucidate these relationships and to understand their underlying mechanisms.
Please see later in the article for the Editors' Summary
Vyšlo v časopise:
Association between Melanocytic Nevi and Risk of Breast Diseases: The French E3N Prospective Cohort. PLoS Med 11(6): e32767. doi:10.1371/journal.pmed.1001660
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pmed.1001660
Souhrn
Background:
While melanocytic nevi have been associated with genetic factors and childhood sun exposure, several observations also suggest a potential hormonal influence on nevi. To test the hypothesis that nevi are associated with breast tumor risk, we explored the relationships between number of nevi and benign and malignant breast disease risk.
Methods and Findings:
We prospectively analyzed data from E3N, a cohort of French women aged 40–65 y at inclusion in 1990. Number of nevi was collected at inclusion. Hazard ratios (HRs) for breast cancer and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. Associations of number of nevi with personal history of benign breast disease (BBD) and family history of breast cancer were estimated using logistic regression. Over the period 15 June 1990–15 June 2008, 5,956 incident breast cancer cases (including 5,245 invasive tumors) were ascertained among 89,902 women. In models adjusted for age, education, and known breast cancer risk factors, women with “very many” nevi had a significantly higher breast cancer risk (HR = 1.13, 95% CI = 1.01–1.27 versus “none”; ptrend = 0.04), although significance was lost after adjustment for personal history of BBD or family history of breast cancer. The 10-y absolute risk of invasive breast cancer increased from 3,749 per 100,000 women without nevi to 4,124 (95% CI = 3,674–4,649) per 100,000 women with “very many” nevi. The association was restricted to premenopausal women (HR = 1.40, ptrend = 0.01), even after full adjustment (HR = 1.34, ptrend = 0.03; phomogeneity = 0.04), but did not differ according to breast cancer type or hormone receptor status. In addition, we observed significantly positive dose–response relationships between number of nevi and history of biopsy-confirmed BBD (n = 5,169; ptrend<0.0001) and family history of breast cancer in first-degree relatives (n = 7,472; ptrend = 0.0003). The main limitations of our study include self-report of number of nevi using a qualitative scale, and self-reported history of biopsied BBD.
Conclusions:
Our findings suggest associations between number of nevi and the risk of premenopausal breast cancer, BBD, and family history of breast cancer. More research is warranted to elucidate these relationships and to understand their underlying mechanisms.
Please see later in the article for the Editors' Summary
Zdroje
1. GreenA, SwerdlowAJ (1989) Epidemiology of melanocytic nevi. Epidemiol Rev 11: 204–221.
2. McGregorB, PfitznerJ, ZhuG, GraceM, EldridgeA, et al. (1999) Genetic and environmental contributions to size, color, shape, and other characteristics of melanocytic naevi in a sample of adolescent twins. Genet Epidemiol 16: 40–53.
3. WachsmuthRC, GautRM, BarrettJH, SaundersCL, Randerson-MoorJA, et al. (2001) Heritability and gene-environment interactions for melanocytic nevus density examined in a U.K. adolescent twin study. J Invest Dermatol 117: 348–352.
4. WachsmuthRC, TurnerF, BarrettJH, GautR, Randerson-MoorJA, et al. (2005) The effect of sun exposure in determining nevus density in UK adolescent twins. J Invest Dermatol 124: 56–62.
5. FalchiM, BatailleV, HaywardNK, DuffyDL, BishopJA, et al. (2009) Genome-wide association study identifies variants at 9p21 and 22q13 associated with development of cutaneous nevi. Nat Genet 41: 915–919.
6. ZhuG, MontgomeryGW, JamesMR, TrentJM, HaywardNK, et al. (2007) A genome-wide scan for naevus count: linkage to CDKN2A and to other chromosome regions. Eur J Hum Genet 15: 94–102.
7. AutierP, BoniolM, SeveriG, GilesG, CattaruzzaMS, et al. (2001) The body site distribution of melanocytic naevi in 6-7 year old European children. Melanoma Res 11: 123–131.
8. DoddAT, MorelliJ, MokrohiskyST, AsdigianN, ByersTE, et al. (2007) Melanocytic nevi and sun exposure in a cohort of Colorado children: anatomic distribution and site-specific sunburn. Cancer Epidemiol Biomarkers Prev 16: 2136–2143.
9. HarrisonSL, BuettnerPG, MacLennanR (1999) Body-site distribution of melanocytic nevi in young Australian children. Arch Dermatol 135: 47–52.
10. WhitemanDC, BrownRM, PurdieDM, HughesMC (2005) Melanocytic nevi in very young children: the role of phenotype, sun exposure, and sun protection. J Am Acad Dermatol 52: 40–47.
11. DennisLK, WhiteE, LeeJA, KristalA, McKnightB, et al. (1996) Constitutional factors and sun exposure in relation to nevi: a population-based cross-sectional study. Am J Epidemiol 143: 248–256.
12. KellyJW, RiversJK, MacLennanR, HarrisonS, LewisAE, et al. (1994) Sunlight: a major factor associated with the development of melanocytic nevi in Australian schoolchildren. J Am Acad Dermatol 30: 40–48.
13. ValiukevicieneS, MisevicieneI, GollnickH (2005) The prevalence of common acquired melanocytic nevi and the relationship with skin type characteristics and sun exposure among children in Lithuania. Arch Dermatol 141: 579–586.
14. DennisLK, WhiteE, McKnightB, KristalA, LeeJA, et al. (1996) Nevi and migration within the United States and Canada: a population-based cross-sectional study. Cancer Causes Control 7: 464–473.
15. FritschiL, McHenryP, GreenA, MackieR, GreenL, et al. (1994) Naevi in schoolchildren in Scotland and Australia. Br J Dermatol 130: 599–603.
16. NguyenTD, SiskindV, GreenL, FrostC, GreenA (1997) Ultraviolet radiation, melanocytic naevi and their dose-response relationship. Br J Dermatol 137: 91–95.
17. RichardMA, GrobJJ, GouvernetJ, CulatJ, NormandP, et al. (1994) [Role of sun exposure on benign melanocytic nevi. A first study in populations controlled for age, sex and phenotype.]. Ann Dermatol Venereol 121: 639–644.
18. RodvallY, WahlgrenCF, UllenH, WiklundK (2007) Common melanocytic nevi in 7-year-old schoolchildren residing at different latitudes in Sweden. Cancer Epidemiol Biomarkers Prev 16: 122–127.
19. DriscollMS, Grant-KelsJM (2007) Hormones, nevi, and melanoma: an approach to the patient. J Am Acad Dermatol 57: 919–931.
20. RubegniP, SbanoP, BurroniM, CeveniniG, BocchiC, et al. (2007) Melanocytic skin lesions and pregnancy: digital dermoscopy analysis. Skin Res Technol 13: 143–147.
21. SlominskiA, TobinDJ, ShibaharaS, WortsmanJ (2004) Melanin pigmentation in mammalian skin and its hormonal regulation. Physiol Rev 84: 1155–1228.
22. GandiniS, SeraF, CattaruzzaMS, PasquiniP, AbeniD, et al. (2005) Meta-analysis of risk factors for cutaneous melanoma: I. Common and atypical naevi. Eur J Cancer 41: 28–44.
23. MellemkjaerL, ChristensenJ, FrederiksenK, PukkalaE, WeiderpassE, et al. (2011) Risk of primary non-breast cancer after female breast cancer by age at diagnosis. Cancer Epidemiol Biomarkers Prev 20: 1784–1792.
24. YangGB, Barnholtz-SloanJS, ChenY, BordeauxJS (2011) Risk and survival of cutaneous melanoma diagnosed subsequent to a previous cancer. Arch Dermatol 147: 1395–1402.
25. MitchellPJ, Perez-NadalesE, MalcolmDS, LloydAC (2003) Dissecting the contribution of p16(INK4A) and the Rb family to the Ras transformed phenotype. Mol Cell Biol 23: 2530–2542.
26. KvaskoffM, MesrineS, Clavel-ChapelonF, Boutron-RuaultMC (2009) Endometriosis risk in relation to naevi, freckles and skin sensitivity to sun exposure: the French E3N cohort. Int J Epidemiol 38: 1143–1153.
27. KvaskoffM, BijonA, MesrineS, Clavel-ChapelonF, Boutron-RuaultMC (2010) Pigmentary traits and risk of endometriosis. Hum Reprod 25: 3157–3158.
28. RedondoP, IdoateM, De FelipeI (1998) Nevi related to thyroid diseases. Arch Intern Med 158: 1577.
29. Clavel-ChapelonF, van LiereMJ, GiuboutC, NiravongMY, GoulardH, et al. (1997) E3N, a French cohort study on cancer risk factors. E3N Group. Etude Epidemiologique aupres de femmes de l'Education Nationale. Eur J Cancer Prev 6: 473–478.
30. VerdeboutJ (2004) A European satellite-derived UV climatology available for impact studies. Radiat Prot Dosimetry 111: 407–411.
31. ResnikS (1967) Melasma induced by oral contraceptive drugs. JAMA 199: 601–605.
32. BorgesV, PuigS, MalvehyJ (2011) [Melanocytic nevi, melanoma, and pregnancy.]. Actas Dermosifiliogr 102: 650–657.
33. BradfordPT, FreedmanDM, GoldsteinAM, TuckerMA (2010) Increased risk of second primary cancers after a diagnosis of melanoma. Arch Dermatol 146: 265–272.
34. GogginsW, GaoW, TsaoH (2004) Association between female breast cancer and cutaneous melanoma. Int J Cancer 111: 792–794.
35. SoerjomataramI, LouwmanWJ, LemmensVE, CoeberghJW, de VriesE (2008) Are patients with skin cancer at lower risk of developing colorectal or breast cancer? Am J Epidemiol 167: 1421–1429.
36. SpanogleJP, ClarkeCA, AronerS, SwetterSM (2010) Risk of second primary malignancies following cutaneous melanoma diagnosis: a population-based study. J Am Acad Dermatol 62: 757–767.
37. WassbergC, ThornM, YuenJ, HakulinenT, RingborgU (1999) Cancer risk in patients with earlier diagnosis of cutaneous melanoma in situ. Int J Cancer 83: 314–317.
38. EwertzM, MouridsenHT (1985) Second cancer following cancer of the female breast in Denmark, 1943–80. Natl Cancer Inst Monogr 68: 325–329.
39. GalperS, GelmanR, RechtA, SilverB, KohliA, et al. (2002) Second nonbreast malignancies after conservative surgery and radiation therapy for early-stage breast cancer. Int J Radiat Oncol Biol Phys 52: 406–414.
40. HarveyEB, BrintonLA (1985) Second cancer following cancer of the breast in Connecticut, 1935–82. Natl Cancer Inst Monogr 68: 99–112.
41. KirovaYM, De RyckeY, GambottiL, PiergaJY, AsselainB, et al. (2008) Second malignancies after breast cancer: the impact of different treatment modalities. Br J Cancer 98: 870–874.
42. MellemkjaerL, FriisS, OlsenJH, SceloG, HemminkiK, et al. (2006) Risk of second cancer among women with breast cancer. Int J Cancer 118: 2285–2292.
43. ProchazkaM, HallP, GranathF, CzeneK (2006) Family history of breast cancer and young age at diagnosis of breast cancer increase risk of second primary malignancies in women: a population-based cohort study. Br J Cancer 95: 1291–1295.
44. RubinoC, de VathaireF, DialloI, ShamsaldinA, LeMG (2000) Increased risk of second cancers following breast cancer: role of the initial treatment. Breast Cancer Res Treat 61: 183–195.
45. SchaapveldM, VisserO, LouwmanMJ, de VriesEG, WillemsePH, et al. (2008) Risk of new primary nonbreast cancers after breast cancer treatment: a Dutch population-based study. J Clin Oncol 26: 1239–1246.
46. SoerjomataramI, LouwmanWJ, de VriesE, LemmensVE, KlokmanWJ, et al. (2005) Primary malignancy after primary female breast cancer in the south of the Netherlands, 1972–2001. Breast Cancer Res Treat 93: 91–95.
47. VolkN, Pompe-KirnV (1997) Second primary cancers in breast cancer patients in Slovenia. Cancer Causes Control 8: 764–770.
48. YuGP, SchantzSP, NeugutAI, ZhangZF (2006) Incidences and trends of second cancers in female breast cancer patients: a fixed inception cohort-based analysis (United States). Cancer Causes Control 17: 411–420.
49. BorgA, SandbergT, NilssonK, JohannssonO, KlinkerM, et al. (2000) High frequency of multiple melanomas and breast and pancreas carcinomas in CDKN2A mutation-positive melanoma families. J Natl Cancer Inst 92: 1260–1266.
50. de SnooFA, HaywardNK (2005) Cutaneous melanoma susceptibility and progression genes. Cancer Lett 230: 153–186.
51. BishopDT, DemenaisF, IlesMM, HarlandM, TaylorJC, et al. (2009) Genome-wide association study identifies three loci associated with melanoma risk. Nat Genet 41: 920–925.
52. TurnbullC, AhmedS, MorrisonJ, PernetD, RenwickA, et al. (2010) Genome-wide association study identifies five new breast cancer susceptibility loci. Nat Genet 42: 504–507.
53. NickelsS, TruongT, HeinR, StevensK, BuckK, et al. (2013) Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors. PLoS Genet 9: e1003284.
54. Agarwal P, Lutful Kabir FM, DeInnocentes P, Bird RC (2012) Tumor suppressor gene p16/INK4A/CDKN2A and its role in cell cycle exit, differentiation, and determination of cell fate. In: Cheng Y, editor. Tumor suppressor genes. Rijeka (Croatia): InTech.
55. Doisneau-SixouSF, SergioCM, CarrollJS, HuiR, MusgroveEA, et al. (2003) Estrogen and antiestrogen regulation of cell cycle progression in breast cancer cells. Endocr Relat Cancer 10: 179–186.
56. LiuT, NiuY, FengY, NiuR, YuY, et al. (2008) Methylation of CpG islands of p16(INK4a) and cyclinD1 overexpression associated with progression of intraductal proliferative lesions of the breast. Hum Pathol 39: 1637–1646.
57. DebniakT, GorskiB, HuzarskiT, ByrskiT, CybulskiC, et al. (2005) A common variant of CDKN2A (p16) predisposes to breast cancer. J Med Genet 42: 763–765.
58. BaxterAJ, HughesMC, KvaskoffM, SiskindV, ShekarS, et al. (2008) The Queensland Study of Melanoma: environmental and genetic associations (Q-MEGA); study design, baseline characteristics, and repeatability of phenotype and sun exposure measures. Twin Res Hum Genet 11: 183–196.
59. GlanzK, SchoenfeldE, WeinstockMA, LayiG, KiddJ, et al. (2003) Development and reliability of a brief skin cancer risk assessment tool. Cancer Detect Prev 27: 311–315.
60. WesterdahlJ, AndersonH, OlssonH, IngvarC (1996) Reproducibility of a self-administered questionnaire for assessment of melanoma risk. Int J Epidemiol 25: 245–251.
61. Clavel-ChapelonF, Dormoy-MortierN (1998) A validation study on status and age of natural menopause reported in the E3N cohort. Maturitas 29: 99–103.
62. RacineA, BijonA, FournierA, MesrineS, Clavel-ChapelonF, et al. (2013) Menopausal hormone therapy and risk of cholecystectomy: a prospective study based on the French E3N cohort. CMAJ 185: 555–561.
63. TehardB, van LiereMJ, Com NougueC, Clavel-ChapelonF (2002) Anthropometric measurements and body silhouette of women: validity and perception. J Am Diet Assoc 102: 1779–1784.
64. KvaskoffM, MesrineS, FournierA, Boutron-RuaultMC, Clavel-ChapelonF (2007) Personal history of endometriosis and risk of cutaneous melanoma in a large prospective cohort of French women. Arch Intern Med 167: 2061–2065.
65. RothmanKJ (1990) No adjustments are needed for multiple comparisons. Epidemiology 1: 43–46.
66. EngelP, FagherazziG, BouttenA, DupreT, MesrineS, et al. (2010) Serum 25(OH) vitamin D and risk of breast cancer: a nested case-control study from the French E3N cohort. Cancer Epidemiol Biomarkers Prev 19: 2341–2350.
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