Epidemiology Research Unit
Centre Hospitalier de I'Universite de Montreal- Hotel-Dieu,
Department of Nutrition, Faculty of Medicine, University of Montreal
American Academy of Neurological and Orthopaedic Surgeons
Characteristics of bone cancer occurrence:
Bone cancer is not a common cancer compared to many other types of
cancer. The principal malignant tumors of bone are: a) osteosarcomas
that occur mostly in the leg bones of children and young adults; this
form is more frequent among girls under 15 and boys over 15; its incidence
is higher among nonwhites than whites(1); b) chondro-sarcomas that
usually afflict people over 40 years of age; this is a slow-growing
tumor that often starts in the pelvic bones; and c) Ewing's sarcoma,
a cancer that impacts mainly children and teenagers; this form infiltrates
large bones such as those of the thigh, upper arm, shin or pelvis;
two times as many males are affected as females; a fast-growing tumor,
its incidence is almost 9-fold higher among whites than blacks.
According to the U.S. Surveillance, Epidemiology and End Results Program(2),
osteosarcomas contribute 36% of all types of bone cancer, followed
by chondrosarcomas and Ewing's sarcomas with around 30% and 16% respectively.
The incidence of osteosarcoma appears to be more frequent in two periods
of life, during adolescence and old age.
the geographical distribution of incidence (Table 1, Figures 1 and
2) and according to the Unit of Descriptive Epidemiology of the International
Agency for Research on Cancer (IARC), only a few countries in Africa
have reliable statistics on bone cancer. Among them, Mali has the
highest standardized rate among males (1.4 per 100,000), while Algeria
exhibits the highest rate among females (1.2 per 100,000), with a
male/female ratio ranging from 0.75 to 1.55(3).
the Americas, Chinese males in Hawaii have the highest incidence rate
of bone cancer (6.4 per 100,000). Actually, this is the highest rate
in the world. Among females, Paraguay has the highest incidence rate
in the region (1.6 per 100,000). The highest male-female ration (9.0)
in the world is found among Japanese Americans in Los Angeles, California.
In the United States, Filipino males and Japanese females have the
lowest incidence rates for bone cancer. Canada has a moderate frequency
rate of bone cancer within the America. In Canada, Quebec seems to
have the highest, and New Brunswick, the lower rate of bone cancer
Europe, Poland (Wilesia) has the highest incidence rate of this disease
in both males and females, with 2.4 and 1.5 per 10,000 respectively,
while Italy shows the lowest rates for males and females. Both France
and Sweden have the highest male/female ratio (3.5).
Australia, the incidence rate of this disease ranges from 0.3 per
100,000 in Tasmanian males to 2.0 in Maori males. In females, except
for Maoris (1.2 per 100,000), most regions have an age standardized
rate below 1.0 per 100,000. In general, this continents has the highest
male/female ratio (around 1.6), indicating a higher incidence rate
of bone cancer among males.
Asia, the Philippines (Manila) has the highest rate of males while
Thailand (Khon Kaen) has the highest frequency in females. It is interesting
that Singapore Indians have the lowest male/female ratio of bone cancer
in the world (0.5), while Israeli on-Jews show the second highest
worldwide male/female ratio (4.0).
brief, among males, Chinese in Hawaii have the highest incidence rate
of bone cancer, while Khon Kaen of Thailand has the highest rate among
women in the world(3).
regard to the mortality rate from bone cancer, we compared existing
statistics on different continents for two time periods (1984-86 and
1994-96). In general, the mortality rate of the world's population
decreased in males from 1.01 to 0.91. In females, the rate in 1984-86
was 0.78, which fell to 0.63 in 1994-96 (Table 2).
mortality rates from bone cancer rose significantly among both males
(from 0.47 to 0.80) and females (from 0.41 to 1.04) in Africa, indicating
a 7% increase among males and an increment of more than 15% among
females for a period of 10 years. Although the number of cases is
small, it still indicates a significant elevation of mortality from
bone cancer. In the Americas, a 0.3% increase in male and a 0.4% rise
in female mortality from bone cancer have been reported. Interestingly,
this disease shows a higher frequency among Asian males compared to
the rate 10 years ago (Table 2); the rate has remained unchanged among
females. The two continents of Europe and Oceania have seen a sharp
and significant decrease of the mortality rate. For example, in Europe,
the rate fell by around 2.4% in males and by 1.8% in females. In Oceania,
these declines were 2.4% in males and 2.9% in females.
rate reduction could be mostly due to better and advanced treatment
of bone cancer as well as disease prevention through public education
and awareness in avoiding known risk factors. In general, it seems
that the mortality rates from bone cancer are decreasing.
Factors for Bone Cancer
Bone cancer comprises around 5% of all cancers among children in developed
countries, particularly in North America and Europe(4). There is little
information about risk factors for bone cancer in adults, while some
data are available on the etiology of this disease among children.
Therefore, in this section, we will review the existing evidence of
risk factors for bone cancer in children.
The possible role of genetics in the etiology of bone cancer was suggest
in a cohort of 850 children with bone cancer in England(5). In a meta-analysis
of five studies, twin cases developed osteosarcoma as well as retinoblastoma(6),
while no twins with Ewing's sarcoma or non-specified bone cancer showed
a affected co-twin. In general, family aggregation of osteosarcoma
is rare. Recently Longhi et al(7) reported four cases of osteosarcoma
in two siblings and in a father and son. These patients had no other
tumors in their family history and had negative p53 mutations.
seems that the frequency of certain types of cancer, such as melanoma
and brain tumors (OR=1.9) or stomach cancer (OR=2.0), is higher among
the first-degree relatives of cases of Ewing' s sarcoma of bone and
a multicentre study of osteosarcoma in the United States and Canada(9),
3% of subjects exhibited germ-line p53 mutations. In another case-control
investigation in Spain(10), a significantly higher proportion of children
with osteosarcoma had HLA-Al1 and HLA-B7 antigens. Such a high frequency
ofHLA-A11 antigen was also found in Japan in 1990(11), while the possible
role of HLA-B7 reported by Barona et al'o was not confirmed by any
Holly et al.(12) observed that regular intake of mixed vitamin supplements
during childhood decreases the risk of bone tumors (RR=0.4; 95%CI
0.1-1.4), but another group(13) reported no association between vitamin
or mineral supplements and bone tumors. Hartley et al(14) examined
the possible role of breast-feeding in bone cancer prevention. They
concluded that there was no association. Several other studies(14-16)
found no association between bone tumors and maternal or paternal
smoking during pregnancy, while another case-control investigation(17)
of Ewing's sarcoma showed that both paternal and maternal smoking
during pregnancy increased the risk of this disease in children. The
relative risk was 2.0 from maternal smoking and 3.7 from paternal
exposure. It should be mentioned here that if both parents were smokers,
the risk was more than 7-fold higher compared with non-smoker parents.
et al.(12) observed no association between maternal smoking during
pregnancy and the risk of osteosarcoma. No association was reported
for maternal alcohol intake during pregnancy and bone cancer in general(14),
Ewing's sarcoma(12) or osteosarcoma(13). Winn et al(17) discerned
no correlation between maternal coffee consumption during pregnancy
and the risk of Ewing's sarcoma.
In a follow-up study of 220 children with tuberculosis treated by
radium-224, around 16% developed bone cancer, particularlyosteosarcoma(18).
In a case-control study(19), no association was found between osteosarcoma
and postnatal exposure to diagnostic ionizing radiation.
There appears to be no association between maternal age, number of
previous pregnancies as well as difficulty of becoming pregnant and
bone cancer(17). Mothers who use medications for nausea and vomiting
during pregnancy have a significantly higher risk of having children
with Ewing's sarcoma.
case-control studies(l3,19) observed no association between maternal
estrogen use in the year before or during pregnancy and the risk of
osteosarcoma in children up to age 24 years.
Schumaker et al. (20) reported an excess of rib abnormalities
among Ewing's sarcoma patients, but not in osteosarcoma cases. A case-control
study in the United States found a high rate of hernias and heart
conditions among Ewing's sarcoma subjects(l7). The high frequency
of hernias occurred early in life. This finding was not confirmed
by another case-control investigation in California(12) or by a comparison
of England and Canada(21).
In a large cohort of male, world class Finnish athletes, with
30 to 60 years of follow-up, no cancer sites showed a significant
excess, but there was a significantly higher risk of sarcoma of the
bone and soft tissue(22). It was suggested that the history of injuries
during their active sports period may have been the major cause of
the high frequency of bone and soft tissue sarcoma.
In general, bone cancer is not a common malignant disease, and perhaps
for this reason its etiology is not known. Furthermore, very few studies
have been conducted in this field. Among different types of bone cancer,
osteosarcomas contribute the highest proportion (36% ), followed by
chondrosarcomas (30%) and Ewing's sarcoma (16%).
highest incidence rate of bone cancer in males is found among American
Chinese in Hawaii. Among females, the population of Khon Kaen in Thailand
exhibits the highestincidence rate of this cancer in the world. American
Japanese have the highest sex ratio for bone cancer, indicating that
the frequency of the disease is 9-fold higher among males than females.
appears to be no consistent association between osteosarcomas and
maternal estrogen use during pregnancy, which has been suspected.
It is also evident that maternal occupation, birth weight and the
presence of congenital anomalies do not playa role in the etiology
on the genetics of bone cancer are not conclusive, but the frequency
of certain types of cancer appears to be higher among the first-degree
relatives of bone cancer cases.
smoking habits during pregnancy may increase the risk of bone cancer
among children. Ionizing radiation heightens the risk of some types
of bone cancer. The possible role of pesticides in the etiology of
bone cancer has been suggested but needs further investigation.
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