title: Variants in melanogenesis-related genes associate with skin cancer risk among Japanese populations.
abstract: Human skin color is known to be associated with the risk of cutaneous cancer. Some reports indicated that pigmentation-related gene variants were associated with cutaneous cancer risk in Caucasian populations, but there are no similar reports in East Asian populations. This study aimed to evaluate the association between pigmentation-related genes and the risk of skin cancer in Japanese populations. We studied the associations between 12 variants of four pigmentation-related genes and melanin index variations in 198 Japanese patients with skin cancer and compared these findings to those of 500 Japanese controls by using multiple logistic regression analysis. Furthermore, we analyzed an independent sample of 107 Japanese patients with skin cancer. A non-synonymous variant, H615R in the oculocutaneous albinism 2 gene (OCA2), was associated with the risk of malignant melanoma in the Yamagata group (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.17-0.86; P = 0.020). Another non-synonymous variant, A481T in OCA2, was associated with the risk of squamous cell carcinoma and actinic keratosis in the Osaka group (OR, 3.16; 95% CI, 1.41-7.04; P = 0.005). In malignant melanoma cases, the minor allele in OCA2 H615R might have induced the development of lesions in sun-exposed skin (OR, 26.32; 95% CI, 1.96-333; P = 0.014). Our results suggest that some OCA2 variants are definite risk factors for the onset of cutaneous cancer in Japanese populations.
authors.affiliation: Department of Dermatology, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Yoshizawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Abe
authors.forename: Naoki
authors.initials: N
authors.lastname: Oiso
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Fukai
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hozumi
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Narita
authors.forename: Tomonori
authors.initials: T
authors.lastname: Motokawa
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Wakamatsu
authors.forename: Shosuke
authors.initials: S
authors.lastname: Ito
authors.forename: Akira
authors.initials: A
authors.lastname: Kawada
authors.forename: Gen
authors.initials: G
authors.lastname: Tamiya
authors.forename: Tamio
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D002280:Basal Cell Carcinoma / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007564:Japan; D008297:Male; D008543:Melanins / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics; D008875:Middle Aged; D012307:Risk Factors; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism; D012880:Skin Pigmentation / Q000235:genetics* / Q000502:physiology
chemical_list: D008543:Melanins; D026901:Membrane Transport Proteins; C489600:OCA2 protein, human
keywords: actinic keratosis; melanoma; oculocutaneous albinism 2; squamous cell carcinoma; variant