title: Nevus density and melanoma risk in women: a pooled analysis to test the divergent pathway hypothesis.
abstract: A "divergent pathway" model for the development of cutaneous melanoma has been proposed. The model hypothesizes that melanomas occurring in people with a low tendency to develop nevi will, on average, arise more commonly on habitually sun-exposed body sites such as the head and neck. In contrast, people with an inherent propensity to develop nevi will tend to develop melanomas most often on body sites with large melanocyte populations, such as on the back. We conducted a collaborative analysis to test this hypothesis using the original data from 10 case-control studies of melanoma in women (2,406 cases and 3,119 controls), with assessment of the potential confounding effects of socioeconomic, pigmentary and sun exposure-related factors. Higher nevus count on the arm was associated specifically with an increased risk of melanoma of the trunk (p for trend = 0.0004) and limbs (both upper and lower limb p for trends = 0.01), but not of the head and neck (p for trend = 0.25). The pooled odds ratios for the highest quartile of nonzero nevus count versus none were 4.6 (95% confidence interval (CI) 2.7-7.6) for melanoma of the trunk, 2.0 (95% CI 0.9-4.5) for the head and neck, 4.2 (95% CI 2.3-7.5) for the upper limbs and 3.4 (95% CI 1.5-7.9) for the lower limbs. Aggregate data from these studies suggest that high nevus counts are strongly associated with melanoma of the trunk but less so if at all of the head and neck. This finding supports different etiologic pathways of melanoma development by anatomic site.
authors.affiliation: Cancer and Population Studies Group, Queensland Institute of Medical Research, Brisbane, Queensland, Australia. Catherine.Olsen@qimr.edu.au
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Olsen
authors.forename: Michael S
authors.initials: MS
authors.lastname: Zens
authors.forename: Therese A
authors.initials: TA
authors.lastname: Stukel
authors.forename: Carlotta
authors.initials: C
authors.lastname: Sacerdote
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Chang
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Armstrong
authors.forename: Veronique
authors.initials: V
authors.lastname: Bataille
authors.forename: Marianne
authors.initials: M
authors.lastname: Berwick
authors.forename: J Mark
authors.initials: JM
authors.lastname: Elwood
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Holly
authors.forename: Connie
authors.initials: C
authors.lastname: Kirkpatrick
authors.forename: Thomas
authors.initials: T
authors.lastname: Mack
authors.forename: Julia Newton
authors.initials: JN
authors.lastname: Bishop
authors.forename: Anne
authors.initials: A
authors.lastname: Østerlind
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Swerdlow
authors.forename: Roberto
authors.initials: R
authors.lastname: Zanetti
authors.forename: Adèle C
authors.initials: AC
authors.lastname: Green
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Karagas
authors.forename: David C
authors.initials: DC
authors.lastname: Whiteman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D005260:Female; D006801:Humans; D008545:Melanoma / Q000175:diagnosis* / Q000453:epidemiology* / Q000473:pathology; D008875:Middle Aged; D008962:Models, Theoretical; D009508:Nevus, Pigmented / Q000175:diagnosis* / Q000453:epidemiology* / Q000473:pathology; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000453:epidemiology* / Q000473:pathology; D012306:Risk; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000453:epidemiology* / Q000473:pathology