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Critical Gene in Calcium Reabsorption: Variants in the KCNJ and SLC12A1 genes – Calcium Intake and Cancer Protection

Posted in Calcium, CANCER BIOLOGY & Innovations in Cancer Therapy, Cancer Genomics, Cancer Prevention: Research & Programs, Cancer Screening, Gene Regulation, Personalized and Precision Medicine & Genomic Research, Population Health Management, Nutrition and Phytochemistry, Variation in human protein-coding regions, tagged American Association for Cancer Research, Cancer - General, Case-control study, Colorectal cancer, Na-K-Cl cotransporter, Roswell Park Cancer Institute, Sanjay Gupta on April 12, 2013| 2 Comments »

Reporter: Aviva Lev-Ari, PhD, RN

Ca Prevention: Calcium May Protect Colon

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco

WASHINGTON — Increasing calcium intake may lower the risk of colorectal adenomas in people who are at increased risk of the precancerous lesions due to variations in two genes, researchers reported here.

In a two-phase, case-control study of nearly 6,000 subjects, high calcium intake was associated with a significantly reduced risk of adenoma among those who carried variants in the KCNJ and SLC12A1 genes.

High calcium intake was not associated with a reduced risk of colorectal adenoma among those with no variants in KCNJ and SLC12A1, both of which are essential to calcium reabsorption in the kidney, reported Xiangzhu Zhu, MD, of Vanderbilt-Ingram Cancer Center at the American Association for Cancer Research meeting here.

The two-phase study was undertaken to explore whether 14 genes involved in calcium homeostasis are associated with the risk for colorectal adenoma. The researchers also wanted to determine whether intake of calcium and magnesium modified any such risks.

To do so, they utilized data from 1,818 cases and 3,992 controls enrolled in the Tennessee Colorectal Polyp Study. Of the 14 genes,KCNJ and SLC12A1 were found to modify the risk between calcium intake and adenomas.

Among the findings:

52% of participants had a variant allele in one of the two genes, and 13% carried variant alleles in both genes.

In people with both gene variants, those the top tertile of calcium intake – consuming 1,300 mg a day or more – had a 69% lower risk of adenoma than people in the lowest tertile, who consumed less than 1,000 mg a day (P for trend=0.039).

In patients who had one gene variant, there was a 39% reduction in adenomas for those in the highest tertile compared with those in the lowest tertile (P for trend=0.046).

The risk for advanced or multiple adenomas were reduced by 89% among those with variants in both genes (P for trend=.01).

If confirmed, the findings suggest that patients who carry one or both variants should increase their calcium intake to at least 1,300 mg per day, either through diet or supplementation, Zhu said.

The findings may also “provide one possible explanation for the inconsistency in previous studies on calcium intake and colorectal abnormalities,” she said.

Further study will be needed to confirm the findings, commented Susan T. Mayne, PhD, of Yale University School of Public Health.

Mayne said the study emphasizes that “one size does not always fit all” when it comes to optimal nutrient intakes.

James R. Marshall, PhD, senior vice president of cancer prevention and population sciences at Roswell Park Cancer Institute in Buffalo, N.Y., agreed, pointing out that studies like this are needed to find biomarkers that can pinpoint those patients most likely to benefit from prevention strategies.

“Case-control studies raise possibilities that help to define which patients to include in future trials,” Marshall said.

Kathleen Struck, MedPage Today Senior Editor, contributed to this article.

The possibility that a supplement such as calcium may prove to be a useful chemoprevention agent is intriguing, but a single study is just a single study — worthy of more investigation. Share your thoughts and read what your colleagues are saying about calcium and colon cancer by clicking the Add Your Knowledge link at the bottom of this article. — Sanjay Gupta, MD

The authors reported no relevant financial disclosures.

Mayne and Marshall reported no relevant financial disclosures.

Primary source: American Association for Cancer Research

SOURCE:
Zhu X, et al “High calcium reduces multiple or advanced colorectal adenoma risk by nearly 90% among those with variant alleles in two critical genes in calcium reabsorption” AACR 2013; Abstract 4832.