Associations between ghrelin and ghrelin receptor polymorphisms and cancer in Caucasian populations: a meta-analysis

BACKGROUND: There is growing evidence that the ghrelin axis, including ghrelin (GHRL) and its receptor, the growth hormone secretagogue receptor (GHSR), play a role in cancer progression. Ghrelin gene and ghrelin receptor gene polymorphisms have been reported to have a range of effects in cancer, from increased risk, to protection from cancer, or having no association. In this study we aimed to clarify the role of ghrelin and ghrelin receptor polymorphisms in cancer by performing a meta-analysis of published case–control studies. We conducted searches of the literature published up to January 2013 in MEDLINE using the PubMed search engine. Individual data on 8,430 cases and 14,008 controls from six case–control studies of an all Caucasian population were evaluated for three ghrelin gene (GHRL; rs696217, rs4684677, rs2075356) and one ghrelin receptor (GHSR; rs572169) polymorphism in breast cancer, esophageal cancer, colorectal cancer and non-Hodgkins lymphoma. RESULTS: In the overall analysis, homozygous and recessive associations indicated that the minor alleles of rs696217 and rs2075356 GHRL polymorphisms conferred reduced cancer risk (odds ratio [OR] 0.61-0.78). The risk was unchanged for breast cancer patients when analysed separately (OR 0.73-0.83). In contrast, the rs4684677 GHRL and the rs572169 GHSR polymorphisms conferred increased breast cancer risk (OR 1.97-1.98, p = 0.08 and OR 1.42-1.43, p = 0.08, respectively). All dominant and co-dominant effects showed null effects (OR 0.96-1.05), except for the rs572169 co-dominant effect, with borderline increased risk (OR 1.08, p = 0.05). CONCLUSIONS: This study suggests that the rs696217 and rs2075356 ghrelin gene (GHRL) polymorphisms may protect carriers against breast cancer, and the rs4684677 GHRL and rs572169 GHSR polymorphisms may increase the risk among carriers. In addition, larger studies are required to confirm these findings.