Possible Gender-Related Modulation by the ROCK1 Gene in Colorectal Cancer Susceptibility

Abstract

Aim: In view of accumulating evidence supporting a pivotal role of the Rho/ROCK pathway in cancer, we investigated Rho-kinase polymorphisms as potential susceptibility factors in colorectal cancer (CRC) in a representative sample of the Italian population. Methods: DNA obtained from the peripheral blood samples of 137 CRC patients and 141 healthy controls was genotyped for four ROCK1 (rs35996865; rs73963110; rs2127958; rs288980) and five ROCK2 (rs12692437; rs7563468; rs35768389; rs17463896; rs16857265) selected single nucleotide polymorphisms. Results: None of the allelic variants of the nine selected markers was associated with the occurrence of CRC or with the development of regional lymph node metastasis. By contrast, the ROCK1 rs35996865 G variant allele was significantly more frequent in male patients (p = 0.028) than in the control group. Conclusion: This finding is, at present, the first that points to a possible gender-related modulation by the ROCK1 gene in CRC susceptibility.

Exosomes of pasteurized milk: potential pathogens of Western diseases

“…It is thus possible that milk exosome-mediated uptake of bovine miR-148a, which is identical with human miR-148a (mirbase.org), targets DNMT1 and thereby attenuates the action of this critical promoter of CRC initiation and progression. Increased expression of Rho-associated coiled coil-containing protein kinase 1 (ROCK1) also plays a key role in CRC pathogenesis [274,275], which as well is a direct target of miR-148a [276].…”

Rho‐kinase Gene Polymorphisms in Related Disease States

“…It is noteworthy that no evidence of an association was found for ROCK2 rs35768389 or for ROCK1 rs73963110 variants, which have been previously described as relevant to colorectal cancer development in a Turkish cohort [13]. On the other hand, Zucchini et al [14]. found that the ROCK1 rs35996865 G variant allele was signiicantly more frequent in male patients than in the control group.…”

“…These data showed that the ROCK1 and ROCK2 genes might be a risk factor for colorectal cancer development, and that genetic polymorphism in these genes may modify individual susceptibility to colorectal cancer in the Turkish population [13]. However, none of the allelic or genotypic variants of the four ROCK1 (rs35996865, rs73963110, rs2127958, and rs288980) and ive ROCK2 (rs12692437, rs7563468, rs35768389, rs17463896, and rs16857265) polymorphisms was found to be associated with the occurrence of colorectal cancer or with the development of regional lymph node metastasis in an Italian population [14]. It is noteworthy that no evidence of an association was found for ROCK2 rs35768389 or for ROCK1 rs73963110 variants, which have been previously described as relevant to colorectal cancer development in a Turkish cohort [13].…”

“…Breast cancer Y405*, S1126* [10] Lung cancer P1193S [10] rs11874761, rs8085504, rs2127958, rs17202375, rs288980 [11] Gastric cancer G285* [12] Colorectal cancer rs73963110, rs35996865 [13] rs35768389, rs73963110, rs2127958, rs288980 [14] rs35996865 (in male patients) [14] V1309* [43] Clear cell renal cell carcinoma rs35996865 [16] rs8089974, rs11874761 [16] Tetralogy of Fallot rs288979, rs56085230 (Tyr269Tyr) [27] rs2292296 (Leu1097Phe), rs7237677, rs7227454, rs288989, rs45449301 (Ile432Val), rs288979, rs17202368, rs17202375, rs2271255 (Lys222Glu), rs1481280, rs8085504, rs398528, rs112165707 (Ser595Ser), rs45562542 (Thr773Ser) [27] Disease…”

“…[13] rs965665, rs2230774, rs6755196, rs1515219 [13] rs12692437, rs7563468, rs35768389, rs17463896, rs16857265 [14] Mantle cell lymphoma rs2290156, rs965665, rs10178332, rs2230774 (Thr431Asn), rs2230774 (Thr431Ser), rs6755196, rs726843 [15] Hypertension rs2230774 (Thr431Asn) [17] rs2230774 (Thr431Asn) [19] rs965665, rs10178332, rs6755196, rs10929732…”