소금과 암 발병Salt and Cancer Risk

Kiwon Kim, Nephrology Clinic, National Cancer Cen-ter

Introduction

American Institute for cancer Research :Food, Nutrition, Physical Activity, and the Prevention of Cancer 2007

Introduction• Salt intake was first reported as a possible risk fac-

tor for stomach cancer in 1959 Bull Inst Public Health 1959; 8: 187-198

• In some early studies, using refrigerators for food storage, which may be an indicator of less salted food consumption or decreased salt intake, was found to be correlated with a reduction in stomach cancer rates Br J Cancer 1990; 62: 136-137

• A nearly linear correlation between the cumulative mortality rate of stomach cancer and the median 24 h urine salt excretion level J Epidemiol 1992; 2: 75-81

Animal Studies• In general, salt alone has no apparent effect on

the development of gastric carcinogenesis,

• But administration of salt in rats induced a con-centration-dependent damage of surface mucous cell layer, and also increased replicative DNA syn-thesis Carcinogenesis 1996; 17: 401-406

Role in the pathogenesis of Gastric Cancer

• Direct damage of the gastric mucosa causing excessive cell replication

• Indirect effect by increasing of the mutagenic potential of N-nitroso compounds (Correa, 1992)

• Damage caused by salt may also increase gastric H. pylori colonization (Fox et al., 1999; Nozaki et al., 2002), which is also sup-portive of an early role in the pathway

Potential Mechanisms• High dietary salt alters viscosity of mucous,

hence facilitating exposure to carcinogenic agents such as nitrates

• Persistent inflammation may promote cell prolif-eration and endogenous mutations

• In the presence of H. pylori infection and atrophic gastritis, high salt exacerbates mucosal damage

Gastric carcinogenesis Model

Salt Intake and Intestinal Meta-plasia

Meta-analyses on the association between salt intake and intestinal metaplasia, and gastric cancer (Dias-Neto et al., 2010; World Cancer Research Fund & Ameri-can Institute for Cancer Research, 2007)

Salt Interacts with H. pylori

Global Stomach Cancer Statistics• Regional variations in

part reflect differ-ences in dietary pat-terns, particularly in European countries, and the prevalence of Helicobacter py-lori infection.

• CA: A Cancer Journal for Clini-ciansVolume 61, Issue 2, pages 69-90, 4 FEB 2011 DOI: 10.3322/caac.20107

Fall of Stomach Cancer rates in US

Global rates of Stomach Cancer in 2002

Maps courtesy of The International Agency for Research on Cancer (IARC) 

Cancer incidence rate in Ko-rea

Reference: Central cancer registry in Korea, Annual report of the central cancer registry in Korea, 2000

Relationship between salt intake as judged by 24h uri-nary salt excretion and stomach cancer mortality in 24

countries

Dietary salt, nitrate and stomach cancer mortality in 24 countries. European Cancer Prevention (ECP) and the INTERSALT Coop-erative Research Group. Int J Epidemiol. 1996;25:494-504

Dietary factors and stomach cancer: a case-control study in Korea

• A case-control investigation involving 213 incident cases of histologically confirmed stomach cancer and an equal number of controls, matched by age (within 2 years) and sex, was conducted from June 1990 to October 1991.

• An increased risk of stomach cancer was noted among those with high consumption of stewed foods such as soybean paste stew and hot pepper-soybean stew, broiled fish, and those who liked salty food.

Int J Epidemiol. 1995 Feb;24(1):33-41. Lee JK, Park BJ, Yoo KY, Ahn YO.

Stomach Cancer among Korean-American

Cancer incidence among Korean-American immigrants in the United States and native Koreans in South Korea. Cancer Control. 2007 Jan;14(1):78-85.

Gastric cancer and salt preference: a population-based cohort study in Korea• Design: Participants were Korean government em-

ployees, school faculty members, and their unem-ployed dependents, aged 30–80 y, who underwent health examinations between 1996 and 1997. In 2003, information on the gastric cancer incidence in these participants was obtained during the 6–7-y follow-up period. The final data analysis included 2,248,129 study subjects

• Result : showed evidence of an increased risk of gas-tric cancer with salt preference. The HRs were 1.10 (95% CI: 1.04, 1.16) and 1.10 (95% CI: 1.03, 1.17) for the overall total population

Am J Clin Nutr 2010;91:1289–93.

Stomach Can-cer In Japan

Death due to Stomach Cancer in Japan

Male FemaleThe amount of salt consumption in Okinawa is far lower than the national average

Stomach Cancer in China

Stomach cancer in 67 Chinese counties

After stratification, positively significant correlations were observed between sodium and stomach cancer mortality in counties with high H. pylori prevalence (≥71.6%) and between H. pylori and stomach cancer mortality in counties with high urinary sodium (≥5.0 mg/mg.creatinine/12-hour)

• 422 gastric cancer cases and 649 community controls. Salt ex-posure was estimated in the year before the onset of symptoms through: sodium intake (estimated by a food frequency ques-tionnaire (FFQ)); main food items/groups contributing to dietary sodium intake; visual analogical scale for salt intake preference; use of table salt; and duration of refrigerator ownership

British Journal of Cancer (2011) 104(1), 198 – 207

Other Cancers ass. with Salt?• Colon cancer• Breast cancer• Pancreas cancer

No sufficient evidence

Chinese-style Salted fish

Conclusion• Most published epidemiological studies provide

positive evidence for an association between salt or salted food consumption and stomach cancer risk

• Ideally, dietary modification of salt intake, as well as eradication of H. pylori infection, is a promising strategy for gastric cancer prevention throughout the world

Benefits of a Reduction in Salt Intake

Reduction inSalt Intake

May reduce

AsthmaAttacks

ReducesStomachCancer

Reduces UrinaryCalcium

ReducesKidney Stones

Reduces Bone

MineralLoss

ReducesOsteoporosis

ReducesFractures

ReducesFluid

Retention

ReducesGlomerular

Hyperfiltration

Reduces

BloodPressure

ReducesCVD

ReducesL.V.H.