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

Pabalan NA, Seim I, Jarjanazi H, Chopin LK - BMC Genet. (2014)

Bottom Line: All dominant and co-dominant effects showed effects (OR 0.96-1.05), except for the rs572169 co-dominant effect, with borderline increased risk (OR 1.08, p = 0.05).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.

View Article: PubMed Central - PubMed

ABSTRACT

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.

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 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.

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Related in: MedlinePlus

Forest plot of homozygous pooled effect in the rs696217 polymorphism. Black diamond denotes the pooled OR. Blue squares indicate the OR in each study, with square sizes directly proportional to the weight contribution (%) of the study. Horizontal lines represent 95% confidence intervals.
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Fig3: Forest plot of homozygous pooled effect in the rs696217 polymorphism. Black diamond denotes the pooled OR. Blue squares indicate the OR in each study, with square sizes directly proportional to the weight contribution (%) of the study. Horizontal lines represent 95% confidence intervals.

Mentions: The overall effects (odd ratios) for the three GHRL polymorphisms (rs696217, rs4684677, rs2075356) and the rs572169 GHSR polymorphism, and the effects observed in breast cancer studies alone are shown in Table 3. Associations were observed mainly in the homozygous and recessive models and not in the dominant model, where the effects were (OR 0.90-1.05, p = 0.19-0.92). Non-significant, decreased risks associated with the rs696217 (OR 0.61-0.63, p = 0.09-0.11) GHRL polymorphism in breast, colorectal, esophageal and colorectal cancer were not altered when analyses were confined to breast cancer studies alone (OR 0.82-0.83, p = 0.57-0.60) (Table 2). For rs696217, all of the study-specific ORs indicate reduced risk (Figure 3) and one study [11] in particular had a one-third weight contribution (33.5%) to the pooled effect (OR 0.63, p = 0.11). Similarly, a non-significant decrease in the risk of the GHRL polymorphism, rs2075356, in breast and colorectal cancer (OR 0.78, p = 0.43-0.45) was unaltered when confined to breast cancer studies (OR 0.78, p = 0.43-0.45) (Table 2). Increased risk in the GHRL SNP rs4684677 (OR 1.97-1.98, p = 0.08) associated with breast and esophageal cancers was exacerbated when confined to breast cancer (OR 2.38-2.40, p = 0.06). Figure 4 shows the contributions of study-specific ORs to the homozygous increased risk pooled effect of rs4684677 (OR 1.98, p = 0.08), mostly (60.6%) attributed to Dossus et al. [11]. On the other hand, the minimal weight contribution (5.3%) of the study by Feigelson et al. [12] is accompanied by wide confidence intervals (95% CI 0.49-169.90). The increased risk associated with the GHSR SNP rs572169 in breast and colorectal cancer (OR 1.42-1.43, p = 0.08) was also increased only when breast cancer was considered (OR 1.69-1.70, p = 0.14). While all of these effects of GHRL SNPs were obtained in zero heterogeneity (I2 = 0%), the effect of rs572169 was heterogeneous (I2 = 68-81%). Figure 5 shows heterogeneity (I2 = 68%) of the rs572169 increased risk pooled effect (OR 1.42, p = 0.08).Table 3


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

Pabalan NA, Seim I, Jarjanazi H, Chopin LK - BMC Genet. (2014)

Forest plot of homozygous pooled effect in the rs696217 polymorphism. Black diamond denotes the pooled OR. Blue squares indicate the OR in each study, with square sizes directly proportional to the weight contribution (%) of the study. Horizontal lines represent 95% confidence intervals.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4228186&req=5

Fig3: Forest plot of homozygous pooled effect in the rs696217 polymorphism. Black diamond denotes the pooled OR. Blue squares indicate the OR in each study, with square sizes directly proportional to the weight contribution (%) of the study. Horizontal lines represent 95% confidence intervals.
Mentions: The overall effects (odd ratios) for the three GHRL polymorphisms (rs696217, rs4684677, rs2075356) and the rs572169 GHSR polymorphism, and the effects observed in breast cancer studies alone are shown in Table 3. Associations were observed mainly in the homozygous and recessive models and not in the dominant model, where the effects were (OR 0.90-1.05, p = 0.19-0.92). Non-significant, decreased risks associated with the rs696217 (OR 0.61-0.63, p = 0.09-0.11) GHRL polymorphism in breast, colorectal, esophageal and colorectal cancer were not altered when analyses were confined to breast cancer studies alone (OR 0.82-0.83, p = 0.57-0.60) (Table 2). For rs696217, all of the study-specific ORs indicate reduced risk (Figure 3) and one study [11] in particular had a one-third weight contribution (33.5%) to the pooled effect (OR 0.63, p = 0.11). Similarly, a non-significant decrease in the risk of the GHRL polymorphism, rs2075356, in breast and colorectal cancer (OR 0.78, p = 0.43-0.45) was unaltered when confined to breast cancer studies (OR 0.78, p = 0.43-0.45) (Table 2). Increased risk in the GHRL SNP rs4684677 (OR 1.97-1.98, p = 0.08) associated with breast and esophageal cancers was exacerbated when confined to breast cancer (OR 2.38-2.40, p = 0.06). Figure 4 shows the contributions of study-specific ORs to the homozygous increased risk pooled effect of rs4684677 (OR 1.98, p = 0.08), mostly (60.6%) attributed to Dossus et al. [11]. On the other hand, the minimal weight contribution (5.3%) of the study by Feigelson et al. [12] is accompanied by wide confidence intervals (95% CI 0.49-169.90). The increased risk associated with the GHSR SNP rs572169 in breast and colorectal cancer (OR 1.42-1.43, p = 0.08) was also increased only when breast cancer was considered (OR 1.69-1.70, p = 0.14). While all of these effects of GHRL SNPs were obtained in zero heterogeneity (I2 = 0%), the effect of rs572169 was heterogeneous (I2 = 68-81%). Figure 5 shows heterogeneity (I2 = 68%) of the rs572169 increased risk pooled effect (OR 1.42, p = 0.08).Table 3

Bottom Line: All dominant and co-dominant effects showed effects (OR 0.96-1.05), except for the rs572169 co-dominant effect, with borderline increased risk (OR 1.08, p = 0.05).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.

View Article: PubMed Central - PubMed

ABSTRACT

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.

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 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.

Show MeSH
Related in: MedlinePlus