BsmI (rs1544410) and FokI (rs2228570) vitamin D receptor polymorphisms, smoking, and body mass index as risk factors of cutaneous malignant melanoma in northeast Italy

Sabina Cauci, Vincenzo Maione, Cinzia Buligan, Martina Linussio, Diego Serraino, Giuseppe Stinco

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)302-318
Number of pages17
JournalCancer Biology and Medicine
Volume14
Issue number3
DOIs
Publication statusPublished - Aug 1 2017

Keywords

  • Body mass index
  • Cutaneous melanoma
  • Metastatic melanoma
  • Obesity
  • Skin cancer
  • Smoking
  • VDR polymorphism
  • Vitamin D receptor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'BsmI (rs1544410) and FokI (rs2228570) vitamin D receptor polymorphisms, smoking, and body mass index as risk factors of cutaneous malignant melanoma in northeast Italy'. Together they form a unique fingerprint.

Cite this