Having older siblings has been linked to a greater risk of early-onset colon cancer in a first-of-its-kind analysis.
Researchers in New York found that people with more older brothers or sisters were also more likely to develop the disease before age 50 – independent of other risk factors.
The analysis of data for 500,000 adults excluded other variables known to increase one’s risk of colon cancer, such as family history of disease, body weight and tobacco use.
The research simply shows an association and cannot say for certain the two factors are linked – but scientists have said the ‘surprising’ link is at least plausible.
Researchers in New York City found that people with two or more older siblings were 1.5 times more likely to develop early-onset colorectal cancer than those who did not have any older siblings
The above graph shows colon cancer cases among under 50s rising by more than 5,500 in 20 years. There is a drop in 2020 because the Covid pandemic led to fewer people coming forward for screenings
One theory is that younger siblings are exposed to more childhood illnesses when lots of brothers and sisters are around.
These stomach bugs may cause damage the gut in a way that make it prone to tumors.
More childhood infections also increases the likelihood of being prescribed antibiotics, which have previously been linked to colon cancers.
Another hypothesis is that parents who have multiple children have a higher chance of passing down genetic mutations that raise the risk of cancer.
The analysis was published in the journal Clinical Gastroenterology and Hepatology as a research letter, meaning it is not a full study.
As such, it did not look at some other risk factors that could be driving colon cancer, including diet and alcohol consumption.
The analysis was carried out by researchers from three New York City institutions – including Memorial Sloan Kettering and Columbia University.
They looked at data from 500,000 adults in the UK Biobank database.
There were fewer than 200 of colon cancers in that group, which could have also affected the findings.
But the team found that people with two or more older siblings were 50 percent more likely to develop early-onset colorectal cancer than those who had none.
People with one older sibling had a 40 percent increased likelihood.
There was no association between colon cancers in people over 50 and how many siblings they had.
Responding to the new findings, Dr Suneel Kamath, an oncologist specializing in early-onset colorectal cancers at the Cleveland Clinic, who was not involved in the research, told DailyMail.com that the research is ‘very surprising’ and ‘it’s hard to know what the cause could be.’
He suggested one theory is that younger siblings are born from older sperm and eggs than their older siblings.
This raises the risk of genetic mutations, which ‘could persist in the child and maybe lead to a cancer earlier in life.’
‘I would add that this finding isn’t particularly useful because we cannot go back in time and “unborn” the older siblings and I doubt many people going forward would limit how many children they have based on these findings,’ he said.
‘It may be useful for young people who present with symptoms suspicious for colorectal cancer, perhaps their doctors if aware of these findings could refer them for a colonoscopy sooner if they are the youngest child in the family.’
‘Bigger and better studies are needed to confirm if these findings are true or not.’
The team said that the ‘drivers of the observed association are unknown,’ though they offered several theories.
Mainly, they believe that having multiple older siblings increases exposure to a variety of childhood illnesses like the flu, Chickenpox, and strep throat.
The team wrote: ‘CRC [colorectal cancer] can take decades to develop.
‘Thus, it is important to understand the role of early life factors, such as socioeconomic status (SES), paternal age, genetics, and microbiome composition.
‘Older siblings may be direct seeding sources of microbiota [bacteria], and recent data show a positive association between number of older siblings and increased gut microbiome diversity.’
The team continued that, if their theory is true, this would increase exposure to antibiotics to treat the bacterial infections.
Recent research suggests the drugs could be partly behind the colorectal cancer surge.
Dr Kamath, previously told DailyMail.com that overusing these medications could alter the gut microbiome, a network of healthy bacteria that help regulate gut and immune health, among other functions.
‘What we suspect is happening is that when there’s excess antibiotic use, there is a change in what was a normal, healthy microbiome, and then bad pathogens, if you will, get introduced into that,’ he said.
‘Those can trigger inflammation or other things that cause mutations in cells.
‘[These] can lead to an overdrive of the cell sort of dividing and replacing itself — and when you do that faster than you should, that can lead to mutations occurring and then tumors forming as a result.’
In one 2021 study reflecting the entire population of Sweden from the year 2005 through the year 2016, researchers identified more than 40,000 colorectal cancer (CRC) cases compared to a matched control group of 200,000 cancer-free Swedes.
Both women and men who took antibiotics for over six months had a 17 percent higher risk of developing cancer in the ascending colon, the first part of the colon to be reached by food after the small intestine, than those who were not prescribed any antibiotics.
Additionally, the researchers noted that people with more older siblings could be at greater risk because their parents were older when they had them versus their siblings, as older populations are most likely to get colorectal cancer. However, they noted that more research is needed to confirm this.
The team has not confirmed if a full study will be released. ‘Findings warrant confirmation in other large study populations,’ the team wrote.
Dr Jen Dunphy, a public health physician and Chief Population Health Officer at Wellness Innovation Network in California who was not involved in the research, told DailyMail.com that while it seemed bizarre, the research is plausible.
She noted that one theory behind the findings is that older children bring more processed food into the home.
‘Generally as kids get older, they have more access to sugary beverages and processed foods both at school through their peers and at home and often these snacks are shared among siblings, exposing younger siblings to these dietary risk factors for colorectal cancer,’ she said.
However, she noted that research would be needed to confirm that.
Data from JAMA Surgery showed that colon cancer is expected to rise by 90 percent in people ages 20 to 34
While the findings seem bizarre, the paper is part of a growing body of research suggesting that birth order and genetics could raise the risk of certain diseases.
A review of more than 238,000 people in 17 countries, for example, found that children whose grandparents were obese were twice as likely to be obese or overweight compared to those with more normal BMIs.
And a study in the Journal of Epidemiology & Community Health found that first-born children were significantly more likely to be overweight or obese than their siblings.
