TY - JOUR
T1 - BsmI (rs1544410) and FokI (rs2228570) vitamin D receptor polymorphisms, smoking, and body mass index as risk factors of cutaneous malignant melanoma in northeast Italy
AU - Cauci, Sabina
AU - Maione, Vincenzo
AU - Buligan, Cinzia
AU - Linussio, Martina
AU - Serraino, Diego
AU - Stinco, Giuseppe
PY - 2017/8/1
Y1 - 2017/8/1
N2 - Objective: To investigate whether vitamin D receptor gene (VDR) BsmI-rs1544410 and FokI-rs2228570 polymorphisms, smoking duration, and body mass index (BMI) are risk factors for cutaneous melanoma, especially metastatic melanoma. Methods: We studied 120 cutaneous melanoma cases [68 stage I and II non-metastatic melanoma (NMetM) patients, plus 52 Stage III and IV metastatic melanoma (MetM) patients], and 120 matching healthy controls from northeast Italy. VDR polymorphisms were measured by restriction fragment length polymorphism analysis. Absence or presence of BsmI and FokI restriction sites was denoted by "B" and "F" or by "b" and "f," respectively. Results: VDR-BsmI bb genotype was more frequent among MetM (32.7%) than among NMetM cases (13.2%), with odds ratio (OR)=3.18. Comparison of all melanoma patients vs healthy controls showed that the following biomarkers were at risk: ≥20 years of smoking (OR=2.43); ≥20 years of smoking combined with bb (OR=4.78), Bb+bb (OR=2.30), Ff (OR=3.04), and Ff+ff (OR=3.08); obesity (BMI>30 kg/m2) alone (OR=3.54); and obesity combined with Bb+bb (OR=3.52), Ff (OR=4.78), and Ff+ff (OR=6.56). Comparison of MetM vs NMetM patients revealed that the following biomarkers were at risk: ≥20 years of smoking (OR=2.39), ≥20 years of smoking combined with bb (OR=5.13), Bb+bb (OR=3.07), and Ff+ff (OR=2.66); and obesity combined with Bb+bb (OR=5.27), Ff (OR=6.28), and Ff+ff (OR=9.18). Triple combination of ≥20 years of smoking, obesity, and Bb+bb yielded OR=9.65 for melanoma patients vs healthy controls and OR=12.2 for MetM vs. NMetM patients. Conclusions: Risk factors for cutaneous MetM include two VDR polymorphisms combined with smoking duration and obesity. Results suggest gene-environment implications in melanoma susceptibility and severity. Future studies in larger cohorts and in subjects with different genetic background are warranted to extend our findings.
AB - Objective: To investigate whether vitamin D receptor gene (VDR) BsmI-rs1544410 and FokI-rs2228570 polymorphisms, smoking duration, and body mass index (BMI) are risk factors for cutaneous melanoma, especially metastatic melanoma. Methods: We studied 120 cutaneous melanoma cases [68 stage I and II non-metastatic melanoma (NMetM) patients, plus 52 Stage III and IV metastatic melanoma (MetM) patients], and 120 matching healthy controls from northeast Italy. VDR polymorphisms were measured by restriction fragment length polymorphism analysis. Absence or presence of BsmI and FokI restriction sites was denoted by "B" and "F" or by "b" and "f," respectively. Results: VDR-BsmI bb genotype was more frequent among MetM (32.7%) than among NMetM cases (13.2%), with odds ratio (OR)=3.18. Comparison of all melanoma patients vs healthy controls showed that the following biomarkers were at risk: ≥20 years of smoking (OR=2.43); ≥20 years of smoking combined with bb (OR=4.78), Bb+bb (OR=2.30), Ff (OR=3.04), and Ff+ff (OR=3.08); obesity (BMI>30 kg/m2) alone (OR=3.54); and obesity combined with Bb+bb (OR=3.52), Ff (OR=4.78), and Ff+ff (OR=6.56). Comparison of MetM vs NMetM patients revealed that the following biomarkers were at risk: ≥20 years of smoking (OR=2.39), ≥20 years of smoking combined with bb (OR=5.13), Bb+bb (OR=3.07), and Ff+ff (OR=2.66); and obesity combined with Bb+bb (OR=5.27), Ff (OR=6.28), and Ff+ff (OR=9.18). Triple combination of ≥20 years of smoking, obesity, and Bb+bb yielded OR=9.65 for melanoma patients vs healthy controls and OR=12.2 for MetM vs. NMetM patients. Conclusions: Risk factors for cutaneous MetM include two VDR polymorphisms combined with smoking duration and obesity. Results suggest gene-environment implications in melanoma susceptibility and severity. Future studies in larger cohorts and in subjects with different genetic background are warranted to extend our findings.
KW - Body mass index
KW - Cutaneous melanoma
KW - Metastatic melanoma
KW - Obesity
KW - Skin cancer
KW - Smoking
KW - VDR polymorphism
KW - Vitamin D receptor
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U2 - 10.20892/j.issn.2095-3941.2017.0064
DO - 10.20892/j.issn.2095-3941.2017.0064
M3 - Article
AN - SCOPUS:85028542646
VL - 14
SP - 302
EP - 318
JO - Cancer Biology and Medicine
JF - Cancer Biology and Medicine
SN - 2095-3941
IS - 3
ER -