Update of preclinical and human studies of calcium and colon cancer prevention

Table 1 Summary of studies on calcium and colon cancer

·Majority of epidemiologic studies suggest protective effect

·In vitro studies: decreased proliferation and increased differentiation and maturation of many types of epithelial cells

·In vivo rodent studies: numerous studies demonstrated inhibition of colonic tumor development preceded by decreased hyperproliferation, ODC and ras mutations, binding of bile and fatty acids into insoluble complexes reducing irritant and hyperproliferative effects, reduced cytotoxicity of fecal water

·Human studies: decreased hyperproliferation in most studies, increased differentiation and maturation of colonic epithelial cells, binding of bile and fatty acids into insoluble complexes, decreased cytotoxicity of fecal water

·Decreased recurrence of human adenomas

Table 2 Dietary calcium effects on epithelial cells in the colon and other organs of rodents

Cell proliferation	References*
Calcium decreased hyperproliferation Gover et al 1994
Calcium: decreased hyperproliferation when induced by doxycholic acid	Wargovich et al 1983
Decreased hyperproliferation when induced by fatty acids	Wargovich et al 1984
Decreased hyperproliferation when induced by cholic acid	Bird et al 1986
Decreased hyperproliferation induced by partial enteric resection	Appleton et al 1986
Decreased deoxycholic acid-induced hyperproliferation	Hu et al 1989
Decreased MNNG-induced hyperproliferation on diet low in fat and calcium	Reshef et al 1990
Decreased hyperproliferation induced by Western-style diet	Newmark et al 1991
Decreased AOM-induced ODC and Tyr K	Arlow et al 1989
Decreased ODC induced by bile acids	Baer et al 1989
Decreased hyperproliferation when induced by Western-style diet	Richter et al[24] 1995
Decreased hyperproliferation in other organs when induced by Western-style diet	Xue et al[25] 1999

*Studies without reference numbers are found in[23].

Table 3 Dietary calcium effects on colonic epithelial cells of rodents

Tumor development	References*
Calcium: decreased tumors induced by partial enteric resection and carcinogen	Appleton et al 1987
Decreased proliferation and tumor formation induced by dietary fat and carcinogen	Pence et al 1988
Decreased intestinal tumors after AMO	Skrypec et al 1988
Decreased colonic tumors induced by AMO	Wargovich et al 1990
Decreased the number of invasive carcinomas after MNU and cholic acid	McSherr y et al 1989
Decreased the number of rats with multiple tumors after DMH	Sitrin et al 1991
Decreased K-ras mutations	Llor et al 1990
Unchanged tumor incidence after DMH	Karkara et al 1989
Unchanged tumor incidence after DMH	Kaup et al 1989
Decreased late-stage precancerous lesion of whole colonic crypt dysplasia	Ri sio et al[26] 1996

*Studies without reference numbers are found in[23].

Table 4 Calcium effects on colonic cell proliferation, differentia tion and cytotoxicity in human subjects

In vitro	References*
Decreased proliferation (2 mM)	Buset et al 1986
Decreased proliferation (2-4 mM)	Appleton et al 1988
Decreased proliferation (2 mM)	Arlow et al 1988
Decreased proliferation (2 mM)	Buset et al 1987
Decreased proliferation (2 mM)	Friedman et al 1989
Protected colonic cells against toxicity of bile acids and fatty acids (5 mM)	Buset et al 1989
Decreased growth of human colon cancer cell lines	Guo et al[27] 1990
Increased histone acetylation: cell differentiation (1-2 mM)	Boffa et al 1989

*Studies without reference numbers are found in[23].

Table 5 Calcium effects on colonic cell proliferation, differentiati on and cytotoxicity of fecal water in human subjects

In vivo	References*
Decreased hyperproliferation	Lipkin et al[28] 1985
Decreased hyperproliferation	Lipkin et al 1989
Decreased hyperproliferation	Rozen et al 1989
Decreased proliferation	Lynch et al 1991
Decreased proliferation	Berger et al 1991
Decreased proliferation	Wargovich et al 1992
Decreased proliferation	Barsoum et al 1992
Decreased proliferation	O’Sullivan et al 1993
Decreased proliferation	Bostick et al 1995
Unchanged proliferation	Gregoire et al 1989
Unchanged proliferation	Cats et al 1995
Decreased ODC	Lans et al[29] 1991
Normalized differentiation-associated lectin binding	Yang et al[30] 1991
Decreased cytotoxicity of fecal water	Govers et al[31] 1996
Increased maturation of colonic epithelial cells	Holt et al[43] 1998
Decreased adenoma recurrence	Baron et al[32] 1999

*Studies without reference numbers are found in[23].