Excess Body Weight Increases Risk for Many Cancers

CME/CE

News Author: Zosia Chustecka

CME Author: Dsire Lie, MD, MSEd
Disclosures

Release Date: February 21, 2008; Valid for credit through February 21, 2009
Credits Available

Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s) for physicians;

Family Physicians - up to 0.25 AAFP Prescribed credit(s) for physicians;
Nurses - 0.25 nursing contact hours (None of these credits is in the area of pharmacology)

To participate in this internet activity: (1) review the target audience, learning objectives, and author disclosures;
(2) study the education content; (3) take the post-test and/or complete the evaluation; (4) view/print certificate
View details.

Learning Objectives
Upon completion of this activity, participants will be able to:
1. Describe the association between body mass index and cancer risk in men and the differences of this
association in women.
2. Describe the association between body mass index and cancer risk in women.

Authors and Disclosures

Zosia Chustecka
Disclosure: Zosia Chustecka has disclosed no relevant financial relationships.

Dsire Lie, MD, MSEd

Disclosure: Dsire Lie, MD, MSEd, has disclosed no relevant financial relationships.

Brande Nicole Martin

Disclosure: Brande Nicole Martin has disclosed no relevant financial information.

February 21, 2008 Excess body weight is becoming increasingly recognized as an important
risk factor of developing cancer. A new study quantifies this risk, showing that weight gain
doubles the risk for certain cancers and increases the risk for many others. As obesity is a
growing problem in developed countries, excess body weight could become the dominant
lifestyle factor that contributes to cancer occurrence, it concludes.

The study is reported in the February 16 issue of The Lancet by Andrew Renehan, PhD,
University of Manchester, United Kingdom, and colleagues. They conducted a systemic review
and meta-analysis of 141 articles, including 282,137 cases of cancer. Using data from these
studies, they calculated the effect of gaining weight equivalent to increase of 5 kg/m 2 in body
mass index (BMI). For a person with an average BMI of 23 kg/m 2, this results in a weight gain of
around 15 kg weight in men and 13 kg in women.

Such a weight gain doubles the risk of developing esophageal adenocarcinoma in both sexes
(relative risk [RR] 1.52, P <.0001). In women, it also slightly more than doubles the risk of
developing endometrial cancer (RR, 1.59; P < .0001) and gallbladder cancer (RR, 1.59; P = .04)
and increases by about a third the risk for renal cancer (RR, 1.34; P < .0001). In men, it
increases the risk for thyroid cancer (RR, 1.33; P = .02), colon cancer (RR, 1.24; P < .0001),
and renal cancer (RR, 1.24; P < .0001).

This amount of weight gain also increased the risk for several other cancers to a smaller extent
(RR, <1.20), as follows: rectal cancer and malignant melanoma in men; postmenopausal breast
cancer, pancreatic, thyroid, and colon cancers in women; and leukaemia, multiple myeloma, and
non-Hodgkin lymphoma in both sexes.
"This comprehensive meta-analysis, which includes many recent published studies, strongly
supports previous evidence that excess bodyweight increases the risk of cancer at most sites,"
according to an accompanying editorial by Sussana Larsson, MSc, and Alicja Wolk, DMSc,
National Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden. "The
findings are strengthened by heterogeneity and sensitivity analyses which show that the
associations were generally consistent across populations," say the editorialists.

National cancer plans should include action points that tackle the obesity epidemic to decrease
cancer incidence and improve survival, the editorialists comment. They suggest that these
action points include education on diet and physical activity; training of health professionals;
restricting advertising on high-calorie and low-nutrient foods; limiting access to unhealthy foods
in schools and workplaces; levying taxes on sugary drinks and other foods high in calories, fat,
or sugar; lowering the process of healthy foods; and promoting physical activity in schools and
workplaces.

Biological Mechanisms to Explain the Link

The mechanisms that link excess weight and cancer risk are not fully understood, according to
the study investigators, but 3 hormonal systems are likely candidates insulin and insulin-like
growth factor (IGF) axis, sex steroids, and adipokines. Other mechanisms may also be involved,
such as localised inflammation, oxidative stress, altered immune response, hypertension, and
the contribution of abdominal obesity to gastroesophageal reflux for esophageal
adenocarcinoma, add the editorialists.

Dr. Andrew Renehan has disclosed that he has received hospitality from several pharmaceutical
companies that make hormone replacements and from Diagnostic Systems Laboratories and
also has received a lecture honorarium from Eli Lilly. The editorialists have disclosed no relevant
financial relationships.

Lancet. 2008;1371:536-537, 569-578.

Clinical Context

According to the current authors, excess body weight defined as a BMI of more than 25 kg/m
(overweight, 25 - 29.9 kg/m; obese, 30 kg/m or higher) is an important risk factor for some
cancers based on evidence from case control and cohort studies. In 2007, the World Cancer
Research Fund used a standardized approach for evidence review to identify esophageal
adenocarcinoma, pancreatic, colorectal, postmenopausal breast, endometrial, renal, and
gallbladder cancers as being associated with increased BMI. The role of ethnicity and sex on
cancer risk associated with BMI is uncertain.

This is a systematic review and meta-analysis to examine prospective observational studies of

20 cancer types at 15 body sites and to derive incidence estimates of risk by BMI increments of
5 kg/m in men and women and by geographic location.

Study Highlights

Medline and EMBASE databases were searched to November 2007 for cohort and
nested case control studies for 20 cancer types.
The cancer types were gastroesophageal, hepatobiliary, leukemia, lung, malignant
melanoma, multiple myeloma, non-Hodgkin's lymphoma, pancreas, renal, thyroid,
prostate, breast, endometrium, and ovary.
Included were studies with risk estimates for men, women, or both, at least 3 categories
of BMI, and self-reported or directly measured weight and height.
Excluded were studies not published as full reports, studies on cancer mortality or those
that reported results only on "all" breast or colorectal cancers, and studies that used
traditional case control designs with recall and interviewer biases.
 5 geographic groups were identified: North America (more than 80% white), European
and Australian, Asia-Pacific, multiethnic, and black American.
Length of follow-up, method for deriving BMI and potential confounders were
considered.
Of 4285 citations, 221 datasets were identified from 141 articles, with 76 cohort studies
(28 from North America, 35 Europe and Australia, and 11 Asia-Pacific).
More than half of all studies were published since 2004.
The analysis included 282,137 incident cancer cases (154,333 men and 127,804
women) of more than 133 million person-years of follow-up.
The mean follow-up per cancer site varied from 8.4 years (breast cancer) to 14.4 years
(multiple myeloma).
In men, increased BMI (per 5 kg/m increment) was strongly associated with
esophageal adenocarcinoma (RR, 1.52; P < .0001) and with thyroid (1.33; P = .02),
colon (1.24;
P < .0001), and renal (1.24; P < .0001) cancers.
There was a weaker positive association for malignant melanoma (1.17; P = .004),
multiple myeloma (1.11; P < .0001), rectal cancer (1.09; P < .0001), leukemia (1.08; P =
.009), and non-Hodgkin lymphoma (1.06; P < .0001).
In women, increased BMI (per 5 kg/m increment) was strongly associated with
endometrial (1.59; P < .0001), gallbladder (1.59; P = .04), and renal (1.34; P < .0001)
cancers and also esophageal adenocarcinoma (1.51; P < .0001).
Weaker positive associations were found in women for leukemia (1.17; P = .01), thyroid
cancers (1.14; P = .0001), postmenopausal breast cancer (1.12; P < .0001), pancreatic
cancer (1.12; P = .01), colon cancer (1.09; P < .0001), and non-Hodgkin's lymphoma
(1.07; P = .05).
Increased BMI was negatively associated with lung cancer, but this was attributed to the
confounding effect of smoking on weight because smokers had a lower BMI than
nonsmokers.
The association of increased BMI with colon and rectal cancers was stronger for men
than women. For renal cancers, the association was stronger in women vs men.
There was a positive association between BMI and premenopausal (P = .009) and
postmenopausal (P = .06) breast cancer in Asia-Pacific populations but an inverse
association for premenopausal breast cancer in the other regions (P = .009).
Results were consistent by random effects or fixed effects model analysis.
The authors concluded that there were sex differences in the association between BMI
and cancer, in particular for colon cancer, and the association was strong for breast
cancer in Asia-Pacific populations.

Pearls for Practice

In men, BMI increment per 5 kg/m is strongly associated with esophageal

adenocarcinoma and with thyroid, colon, and renal cancers. The association with colon
cancer was stronger in men than women. For renal cancer, the association was
stronger in women vs men.
In women, BMI increase is strongly associated with endometrial, gallbladder, and renal
cancers and with esophageal adenocarcinoma. Breast cancer is associated with
increased BMI in Asia-Pacific populations.