Hand-Me-Down H. Pylori from Siblings Tied to Stomach Cancer

NEW YORK, Jan 16 -- Men from large families, particularly those who are the youngest siblings, are at an increased risk for Helicobacter pylori-related stomach cancer, researchers here said.

For certain men with the most virulent cagA-positive strain of H. pylori, gastric cancer risk was more than twice as high among those with six or more siblings, versus two or fewer (odds ratio 2.2, 95% confidence interval 1.2 to 4.0), reported Martin J. Blaser, M.D., of New York University, and colleagues, in the Jan. 16 issue of the online journal Public Library of Science Medicine.

"The associations with large sibships and with later birth order could imply that the affected individuals acquired the relevant H. pylori strain as a child from an older sibling," Dr. Blaser and colleagues wrote.

The mechanism may be that siblings acquire "preadapted" bacteria at a time when their immune system is not fully matured, they said. H. pylori often infect people early in childhood either orally or through contact with feces.

The researchers followed-up on a cohort of more than 7,000 Japanese-American men in Hawaii who were initially examined 28 years previously. The 261 men who had developed incident gastric cancer were matched by age and examination date with controls who did not develop stomach cancer.

Each case was confirmed by examination of tissue obtained from surgery or biopsy. The mean age at diagnosis was 72.7. Participants whose blood sample tested positive for H. pylori or the CagA protein were defined as H. pylori positive.

The researchers reconfirmed the significant link between gastric cancer and H. pylori found in a previous analysis. The findings were:

• Among the 261 men who later developed stomach cancer, 92% carried H. pylori at baseline and 72% carried cagA-positive strains.
• In the control group, 79% carried H. pylori and 59% carried cagA-positive strains.
• The presence of H. pylori thus increased the odds of developing gastric cancer by 2.97-fold (95% CI 1.70 to 5.21).
• The presence of cagA-positive H. pylori strains increased the odds 1.80-fold (95% CI 1.22 to 2.64).

Although the overall group showed no significant link between family size and gastric cancer risk, there were significant associations among H. pylori carriers. The researchers reported:

• Among H. pylori-positive men, the odds for any type of gastric cancer were 1.2 (95% 0.7 to 2.1) for those with three to five siblings and 1.7 (95% CI 1.0 to 2.9) for those with six or more siblings, compared with a sibship of one to three (P for trend=0.05).
• Among cagA-positive men, the odds for any type of gastric cancer were 1.2 (95% CI 0.7 to 2.2) for those with three to five siblings and 2.2 (95% CI 1.2 to 4.0) for those with six or more siblings, compared with a sibship of one to three (P for trend=0.01), and
• The relationships were not significant for specific subtypes of gastric cancer among participants with any H. pylori strain (P=0.20 for intestinal-type and P=0.13 for diffuse-type) or with cagA-positive strains (P=0.10 for intestinal-type and P=0.09 for diffuse-type).

Being born into an already large family increased risk of intestinal-type gastric cancer. Men with any H. pylori strain tended to be more prone to intestinal-type gastric cancer with higher birth order (P for trend=0.06).

This risk became significant for those with the most virulent cagA-positive strain (P for trend=0.01). Compared with having no older siblings, the odds ratios for intestinal-type stomach cancer by sibship size were:

• 1.9 for one or two older siblings (95% CI 0.9 to 3.7).
• 2.8 for three or more older siblings (95% CI 1.2 to 6.1).

"Microbial genomes are plastic, and H. pylori is especially so," they wrote. "Passage through a host selects for particular genotypes, and the spreading of these genotypes to a genetically related host may lead to a better adapted, and thus more virulent, bacterial population than occurs when transmitted from an unrelated individual."

However, they acknowledged that "large sibships may be a marker for low socioeconomic status," or for factors such as other childhood infections or stresses associated with extra siblings. The investigators said that earlier acquisition and thus longer total colonization by a few years is probably not as important as acquisition of "preadapted" bacteria.

The study only included men of a particular ethnic and socioeconomic group, which may reduce confounding but also decrease applicability to the general population, the researchers said.